Golimumab
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gloria Picoy [2]
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Black Box Warning
|
WARNING: SERIOUS INFECTIONS AND MALIGNANCY
See full prescribing information for complete Boxed Warning.
====Serious infections====
Patients treated with golimumab are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue golimumab if a patient develops a serious infection. Reported infections with TNF-blockers, of which golimumab is a member, include:
Consider the risks and benefits of treatment with golimumab prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with golimumab, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. MalignancyLymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which golimumab is a member. |
Overview
Golimumab is a tumor necrosis factor inhibitor that is FDA approved for the treatment of moderately to severely active rheumatoid arthritis (RA), active psoriatic arthritis (PsA), active ankylosing spondylitis (AS); and moderate to severe Ulcerative colitis (UC) with an inadequate response or intolerant to prior treatment or requiring continuous steroid therapy. There is a Black Box Warning for this drug as shown here. Common adverse reactions include upper respiratory tract infection, nasopharyngitis and injection site reactions.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Rheumatoid Arthritis
- Golimumab, in combination with methotrexate, is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis.
- Dosage: 50 mg administered by subcutaneous injection once a month
Psoriatic Arthritis
- Golimumab, alone or in combination with methotrexate, is indicated for the treatment of adult patients with active psoriatic arthritis.
- Dosage: 50 mg administered by subcutaneous injection once a month
Ankylosing Spondylitis
- Golimumab is indicated for the treatment of adult patients with active ankylosing spondylitis.
- Dosage: 50 mg administered by subcutaneous injection once a month
Ulcerative Colitis
- Golimumab is indicated in adult patients with moderately to severely active ulcerative colitis who have demonstrated corticosteroid dependence or who have had an inadequate response to or failed to tolerate oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine for:
- inducing and maintaining clinical response
- improving endoscopic appearance of the mucosa during induction
- inducing clinical remission
- achieving and sustaining clinical remission in induction responders
- Dosage: 200 mg subcutaneous injection at Week 0, followed by 100 mg at Week 2 and then maintenance therapy with 100 mg every 4 weeks.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Golimumab in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Golimumab in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Safety and effectiveness of golimumab have not been established in pediatric patients younger than 18 years
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Golimumab in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Golimumab in pediatric patients.
Contraindications
None
Warnings
|
WARNING: SERIOUS INFECTIONS AND MALIGNANCY
See full prescribing information for complete Boxed Warning.
====Serious infections====
Patients treated with golimumab are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue golimumab if a patient develops a serious infection. Reported infections with TNF-blockers, of which golimumab is a member, include:
Consider the risks and benefits of treatment with golimumab prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with golimumab, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. MalignancyLymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which golimumab is a member. |
Serious Infections
Patients treated with golimumab are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death.
Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, or parasitic organisms including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, and tuberculosis have been reported with TNF-blockers. Patients have frequently presented with disseminated rather than localized disease. The concomitant use of a TNF-blocker and abatacept or anakinra was associated with a higher risk of serious infections; therefore, the concomitant use of golimumab and these biologic products is not recommended.
Treatment with golimumab should not be initiated in patients with an active infection, including clinically important localized infections. Patients greater than 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants such as corticosteroids or methotrexate may be at greater risk of infection. Consider the risks and benefits of treatment prior to initiating golimumab in patients:
- with chronic or recurrent infection;
- who have been exposed to tuberculosis;
- with a history of an opportunistic infection;
- who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or
- with underlying conditions that may predispose them to infection.
Serious Infection in Clinical Trials
In controlled Phase 3 trials through Week 16 in patients with RA, PsA, and AS, serious infections were observed in 1.4% of golimumab-treated patients and 1.3% of control-treated patients. In the controlled Phase 3 trials through Week 16 in patients with RA, PsA, and AS, the incidence of serious infections per 100 patient-years of follow-up was 5.7 (95% CI: 3.8, 8.2) for the golimumab group and 4.2 (95% CI: 1.8, 8.2) for the placebo group. In the controlled Phase 2/3 trial through Week 6 of golimumab induction in UC, the incidence of serious infections in golimumab 200/100 mg-treated patients was similar to the incidence of serious infections in placebo-treated patients. Through Week 60, the incidence of serious infections was similar in patients who received golimumab induction and 100 mg during maintenance compared with patients who received golimumab induction and placebo during the maintenance portion of the UC trial. Serious infections observed in golimumab-treated patients included sepsis, pneumonia, cellulitis, abscess, tuberculosis, invasive fungal infections, and hepatitis B infection.
Tuberculosis
Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving TNF-blockers, including patients who have previously received treatment for latent or active tuberculosis. Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating golimumab and periodically during therapy.
Treatment of latent tuberculosis infection prior to therapy with TNF-blockers has been shown to reduce the risk of tuberculosis reactivation during therapy. Prior to initiating golimumab, assess if treatment for latent tuberculosis is needed; an induration of 5 mm or greater is a positive tuberculin skin test, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG).
Consider anti-tuberculosis therapy prior to initiation of golimumab in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient.
Cases of active tuberculosis have occurred in patients treated with golimumab during and after treatment for latent tuberculosis. Monitor patients for the development of signs and symptoms of tuberculosis including patients who tested negative for latent tuberculosis infection prior to initiating therapy, patients who are on treatment for latent tuberculosis, or patients who were previously treated for tuberculosis infection.
Consider tuberculosis in the differential diagnosis in patients who develop a new infection during golimumab treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis.
In the controlled and uncontrolled portions of the Phase 2 RA and Phase 3 RA, PsA, and AS trials, the incidence of active TB was 0.23 and 0 per 100 patient-years in 2347 golimumab-treated patients and 674 placebo-treated patients, respectively. Cases of TB included pulmonary and extra pulmonary TB. The overwhelming majority of the TB cases occurred in countries with a high incidence rate of TB. In the controlled Phase 2/3 trial of golimumab induction through Week 6 in UC, no cases of TB were observed in golimumab 200/100 mg-treated patients or in placebo-treated patients. Through Week 60, the incidence per 100 patient-years of TB in patients who received golimumab induction and 100 mg during the maintenance portion of the UC trial was 0.52 (95% CI: 0.11, 1.53). One case of TB was observed in the placebo maintenance group in a patient who received golimumab intravenous (IV) induction.
Invasive Fungal Infections
If patients develop a serious systemic illness and they reside or travel in regions where mycoses are endemic, consider invasive fungal infection in the differential diagnosis. Consider appropriate empiric antifungal therapy and take into account both the risk for severe fungal infection and the risks of antifungal therapy while a diagnostic workup is being performed. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. To aid in the management of such patients, consider consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections.
Hepatitis B Virus Reactivation
The use of TNF-blockers including golimumab has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic hepatitis B carriers (i.e., surface antigen positive). In some instances, HBV reactivation occurring in conjunction with TNF-blocker therapy has been fatal. The majority of these reports have occurred in patients who received concomitant immunosuppressants.
All patients should be tested for HBV infection before initiating TNF-blocker therapy. For patients who test positive for hepatitis B surface antigen, consultation with a physician with expertise in the treatment of hepatitis B is recommended before initiating TNF-blocker therapy. The risks and benefits of treatment should be considered prior to prescribing TNF-blockers, including golimumab, to patients who are carriers of HBV. Adequate data are not available on whether anti-viral therapy can reduce the risk of HBV reactivation in HBV carriers who are treated with TNF-blockers. Patients who are carriers of HBV and require treatment with TNF-blockers should be closely monitored for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy.
In patients who develop HBV reactivation, TNF-blockers should be stopped and antiviral therapy with appropriate supportive treatment should be initiated. The safety of resuming TNF-blockers after HBV reactivation has been controlled is not known. Therefore, prescribers should exercise caution when considering resumption of TNF-blockers in this situation and monitor patients closely.
Malignancies
Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy ≤ 18 years of age), of which golimumab is a member. Approximately half the cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression, and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months (range 1 to 84 months) after the first dose of TNF blocker therapy. Most of the patients were receiving concomitant immunosuppressants. These cases were reported post-marketing and are derived from a variety of sources, including registries and spontaneous postmarketing reports.
The risks and benefits of TNF-blocker treatment including golimumab should be considered prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing a TNF-blocker in patients who develop a malignancy.
In the controlled portions of clinical trials of TNF-blockers including golimumab, more cases of lymphoma have been observed among patients receiving anti-TNF treatment compared with patients in the control groups. During the controlled portions of the Phase 2 trials in RA, and the Phase 3 trials in RA, PsA and AS, the incidence of lymphoma per 100 patient-years of follow-up was 0.21 (95% CI: 0.03, 0.77) in the combined golimumab group compared with an incidence of 0 (95% CI: 0., 0.96) in the placebo group. In the controlled and uncontrolled portions of these clinical trials in 2347 golimumab-treated patients with a median follow-up of 1.4 years, the incidence of lymphoma was 3.8-fold higher than expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race).1 Through Week 60 of the UC trials, there were no cases of lymphoma with golimumab. Patients with RA and other chronic inflammatory diseases, particularly patients with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF-blocking therapy. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use in rheumatoid arthritis and other indications. Even in the absence of TNF blocker therapy, patients with rheumatoid arthritis may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia.
Rare post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF-blocking agents. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. Nearly all of the reported TNF-blocker associated cases have occurred in patients with Crohn's disease or ulcerative colitis. The majority were in adolescent and young adult males. Almost all these patients had received treatment with azathioprine (AZA) or 6-mercaptopurine (6–MP) concomitantly with a TNF blocker at or prior to diagnosis. The potential risk with the combination of AZA or 6-MP and golimumab should be carefully considered. A risk for the development for hepatosplenic T-cell lymphoma in patients treated with TNF-blockers cannot be excluded.
During the controlled portions of the Phase 2 trial in RA, and the Phase 3 trials in RA, PsA and AS, the incidence of malignancies other than lymphoma per 100 patient-years of follow-up was not elevated in the combined golimumab group compared with the placebo group. In the controlled and uncontrolled portions of these trials, the incidence of malignancies, other than lymphoma, in golimumab-treated patients was similar to that expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race).1 In the 6-week placebo-controlled portions of the golimumab Phase 2/3 clinical trials in UC, the incidence of non-lymphoma malignancies (excluding non-melanoma skin cancer) was similar between the golimumab and the placebo group. Through Week 60, the incidence of non-lymphoma malignancies (excluding non-melanoma skin cancer) was similar to the general U.S. population according to the SEER database (adjusted for age, gender, and race). Short follow-up periods, such as those of one year or less in the studies above, may not adequately reflect the true incidence of malignancies.
It is not known if golimumab treatment influences the risk for developing dysplasia or colon cancer. All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma (for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), or who had a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular intervals before therapy and throughout their disease course. This evaluation should include colonoscopy and biopsies per local recommendations. In patients with newly diagnosed dysplasia treated with golimumab, the risks and benefits to the individual patient must be carefully reviewed and consideration should be given to whether therapy should be continued.
Melanoma has been reported in patients treated with TNF-blocking agents, including golimumab. Merkel cell carcinoma has been reported in patients treated with TNF-blocking agents. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.
In controlled trials of other TNF-blockers in patients at higher risk for malignancies (e.g., patients with COPD, patients with Wegener's granulomatosis treated with concomitant cyclophosphamide) a greater portion of malignancies occurred in the TNF-blocker group compared to the controlled group. In an exploratory 1-year clinical trial evaluating the use of 50, 100 and 200 mg of golimumab in 309 patients with severe persistent asthma, 6 patients developed malignancies other than NMSC in the golimumab groups compared to none in the control group. Three of the 6 patients were in the 200 mg golimumab group.
Congestive Heart Failure
Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF-blockers, including golimumab. In several exploratory trials of other TNF-blockers in the treatment of CHF, there were greater proportions of TNF-blocker treated patients who had CHF exacerbations requiring hospitalization or increased mortality. golimumab has not been studied in patients with a history of CHF and golimumab should be used with caution in patients with CHF. If a decision is made to administer golimumab to patients with CHF, these patients should be closely monitored during therapy, and golimumab should be discontinued if new or worsening symptoms of CHF appear.
Demyelinating Disorders
Use of TNF-blockers, of which golimumab is a member, has been associated with rare cases of new onset or exacerbation of central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS) and peripheral demyelinating disorders, including Guillain-Barré syndrome. Cases of central demyelination, MS, optic neuritis, and peripheral demyelinating polyneuropathy have rarely been reported in patients treated with golimumab. Prescribers should exercise caution in considering the use of TNF-blockers, including golimumab, in patients with central or peripheral nervous system demyelinating disorders. Discontinuation of golimumab should be considered if these disorders develop.
Use with Abatacept
In controlled trials, the concurrent administration of another TNF-blocker and abatacept was associated with a greater proportion of serious infections than the use of a TNF-blocker alone; and the combination therapy, compared to the use of a TNF-blocker alone, has not demonstrated improved clinical benefit in the treatment of RA. Therefore, the combination of TNF-blockers including golimumab and abatacept is not recommended.
Use with Anakinra
Concurrent administration of anakinra (an interleukin-1 antagonist) and another TNF-blocker, was associated with a greater portion of serious infections and neutropenia and no additional benefits compared with the TNF-blocker alone. Therefore, the combination of anakinra with TNF-blockers, including golimumab, is not recommended.
Switching Between Biological Disease Modifying Antirheumatic Drugs
Care should be taken when switching from one biological product to another biological product since overlapping biological activity may further increase the risk of infection.
Hematologic Cytopenias
There have been post-marketing reports of pancytopenia, leukopenia, neutropenia, aplastic anemia, and thrombocytopenia in patients receiving TNF-blockers. In clinical trials, cases of pancytopenia, leukopenia, neutropenia, and thrombocytopenia have also occurred in golimumab-treated patients. Caution should be exercised when using TNF-blockers, including golimumab, in patients who have or have had significant cytopenias.
Vaccinations/Therapeutic Infectious Agents
Live Vaccines
Patients treated with golimumab may receive vaccinations, except for live vaccines. In patients receiving anti-TNF therapy, limited data are available on the response to live vaccination, or on the secondary transmission of infection by live vaccines. Use of live vaccines could result in clinical infections, including disseminated infections.
Therapeutic Infectious Agents
Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder instillation for the treatment of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious agents not be given concurrently with golimumab.
Non-live Vaccines
In the Phase 3 PsA trial, after pneumococcal vaccination, a similar proportion of golimumab-treated and placebo-treated patients were able to mount an adequate immune response of at least a 2-fold increase in antibody titers to pneumococcal polysaccharide vaccine. In both golimumab-treated and placebo-treated patients, the proportions of patients with response to pneumococcal vaccine were lower among patients receiving MTX compared with patients not receiving MTX. The data suggest that golimumab does not suppress the humoral immune response to the pneumococcal vaccine.
Hypersensitivity Reactions
In post-marketing experience, serious systemic hypersensitivity reactions (including anaphylactic reaction) have been reported following golimumab administration. Some of these reactions occurred after the first administration of golimumab. If an anaphylactic or other serious allergic reaction occurs, administration of golimumab should be discontinued immediately and appropriate therapy instituted.
Adverse Reactions
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety data described below are based on 5 pooled, randomized, double-blind, controlled Phase 3 trials in patients with RA, PsA, and AS (Trials RA-1, RA-2, RA-3, PsA, and AS). These 5 trials included 639 control-treated patients and 1659 golimumab-treated patients including 1089 with RA, 292 with PsA, and 278 with AS. The safety data in 1233 golimumab-treated patients with ulcerative colitis from 3 pooled, randomized, double-blind, controlled Phase 2/3 trials are also described below (Trials UC-1, UC-2, and UC-3). The proportion of patients who discontinued treatment due to adverse reactions in the controlled Phase 3 trials through Week 16 in RA, PsA and AS was 2% for golimumab-treated patients and 3% for placebo-treated patients. The most common adverse reactions leading to discontinuation of golimumab in the controlled Phase 3 trials in RA, PsA and AS through Week 16 were sepsis (0.2%), alanine aminotransferase increased (0.2%), and aspartate aminotransferase increased (0.2%). The most common adverse drug reactions leading to discontinuation through Week 60 of the UC trials in patients who received golimumab induction and 100 mg during maintenance compared with patients who received golimumab induction and placebo during maintenance were tuberculosis (0.3% vs 0.6%) and anemia (0.3% vs 0%), respectively.
The most serious adverse reactions were:
- Serious Infections
- Malignancies
Upper respiratory tract infection and nasopharyngitis were the most common adverse reactions reported in the combined Phase 3 RA, PsA and AS trials through Week 16, occurring in 7% and 6% of golimumab-treated patients as compared with 6% and 5% of control-treated patients, respectively.
Infections
In controlled Phase 3 trials through Week 16 in RA, PsA, and AS, infections were observed in 28% of golimumab-treated patients compared to 25% of control-treated patients. For serious infections, see the Warnings and Precautions section. In the controlled Phase 2/3 trial of golimumab induction through Week 6 in UC, the rates of infections were similar in golimumab 200/100 mg-treated patients and placebo-treated patients, or approximately 12%. Through Week 60, the incidence per patient year of infections was similar in patients who received golimumab induction and 100 mg during maintenance compared with patients who received golimumab induction and placebo during the maintenance portion of the UC trial.
Demyelinating Disorders
In the controlled Phase 2/3 trial of golimumab induction through Week 6, no cases of demyelination were observed in golimumab 200/100 mg-treated patients or placebo-treated patients. Through Week 60, there were no cases of demyelination in the golimumab 100 mg group during maintenance. One case of CNS demyelination was observed in the placebo maintenance group in a patient who received golimumab 400/200 mg during induction.
Liver Enzyme Elevations
There have been reports of severe hepatic reactions including acute liver failure in patients receiving TNF-blockers. In controlled Phase 3 trials of golimumab in patients with RA, PsA, and AS through Week 16, ALT elevations ≥ 5 × ULN occurred in 0.2% of control-treated patients and 0.7% of golimumab-treated patients and ALT elevations ≥ 3 × ULN occurred in 2% of control-treated patients and 2% of golimumab-treated patients. Since many of the patients in the Phase 3 trials for RA, PsA, and AS were also taking medications that cause liver enzyme elevations (e.g., NSAIDs, MTX), the relationship between golimumab and liver enzyme elevation is not clear.
In Phase 2/3 UC trials, the incidence of ALT elevations ≥ 5 × ULN was similar in golimumab-treated patients and placebo-treated patients, or approximately 1%, with an average duration of follow-up of 46 weeks and 18 weeks, respectively. ALT elevations ≥ 3 × ULN occurred in 2.0% of golimumab-treated patients compared with 1.5% of placebo-treated patients with an average duration of follow-up of 46 weeks and 18 weeks, respectively.
Autoimmune Disorders and Autoantibodies
The use of TNF-blockers, including golimumab, has been associated with the formation of autoantibodies and, rarely, with the development of a lupus-like syndrome. In the controlled Phase 3 trials in patients with RA, PsA, and AS through Week 14, there was no association of golimumab treatment and the development of newly positive anti-dsDNA antibodies. In Phase 3 trials in RA, PsA, and AS through 1 year of follow up, 4.0% of golimumab-treated patients and 2.6% of control patients were newly ANA-positive (at titers of 1:160 or greater). The frequency of anti-dsDNA antibodies at 1 year of follow up was uncommon in patients who were anti-dsDNA negative at baseline. Through Week 60 of the UC trials, 3.5% of patients who received golimumab induction and 100 mg during maintenance were newly ANA-positive (at titers of 1:160 or greater) compared with 3.5% of patients who received golimumab induction and placebo during the maintenance portion of the UC trial. The frequency of anti-dsDNA antibodies at 1 year of follow up in patients who were anti-dsDNA negative at baseline was 0.5% in patients receiving golimumab induction and 100 mg during maintenance compared with 0% in patients who received golimumab induction and placebo during maintenance.
Injection Site Reactions
In controlled Phase 3 trials through Week 16 in RA, PsA and AS, 6% of golimumab-treated patients had injection site reactions compared with 2% of control-treated patients. The majority of the injection site reactions were mild and the most frequent manifestation was injection site erythema.
In the controlled Phase 2/3 trial through Week 6 in UC, 3.4% of golimumab-treated patients had injection site reactions compared with 1.5% in control-treated patients. The majority of the injection site reactions were mild and moderate and the most frequent manifestation was injection site erythema.
In controlled Phase 2 and 3 trials in RA, PsA, AS, and Phase 2/3 UC trials, no patients treated with golimumab developed anaphylactic reactions.
Immunogenicity
Antibodies to golimumab were detected in 57 (4%) of golimumab-treated patients across the Phase 3 RA, PsA, and AS trials through Week 24. Similar rates were observed in each of the three indications. Patients who received golimumab with concomitant MTX had a lower proportion of antibodies to golimumab than patients who received golimumab without MTX (approximately 2% versus 7%, respectively).
The presence of serum concentrations of golimumab can interfere with the detection of antibodies to golimumab leading to inconclusive results. In UC trials, 34 (3%), 341 (28%) and 823 (69%) of golimumab-treated subjects were positive, negative and inconclusive for antibodies to golimumab, respectively. Treatment with concomitant immunomodulators (AZA, 6-MP and MTX) resulted in a lower proportion of patients with antibodies to golimumab than patients receiving golimumab without immunomodulators (2% versus 4%, respectively).
Of the patients with a positive antibody response to golimumab in the Phase 2 and 3 trials, most were determined to have neutralizing antibodies to golimumab as measured by a cell-based functional assay.
The small number of patients positive for antibodies to golimumab limits the ability to draw definitive conclusions regarding the relationship between antibodies to golimumab and clinical efficacy or safety measures.
The data above reflect the percentage of patients whose test results were considered positive for antibodies to golimumab in an ELISA assay, and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to golimumab with the incidence of antibodies to other products may be misleading.
Other Adverse Reactions
Table 1 summarizes the adverse drug reactions that occurred at a rate of at least 1% in the golimumab ± DMARD group and with a higher incidence than in the placebo ± DMARD group during the controlled period of the 5 pooled Phase 3 trials through Week 16 in patients with RA, PsA, and AS.
Less common clinical trial adverse drug reactions
Adverse drug reactions that occurred <1% in golimumab-treated patients during the golimumab clinical trials that do not appear in the Warnings and Precautions section included the following events listed by system organ class:
- Infections and infestations: Septic shock, atypical mycobacterial infection, pyelonephritis, arthritis bacterial, bursitis infective
- Neoplasms benign, malignant and unspecified: Leukemia
- Skin and subcutaneous tissue disorders: Psoriasis (new onset or worsening, palmar/plantar and pustular), vasculitis (cutaneous)
- Vascular disorders: Vasculitis (systemic)
Other clinical trial adverse drug reactions in ulcerative colitis clinical trials
In the Phase 2/3 trials in UC evaluating 1233 golimumab-treated patients, no new adverse drug reactions were identified and the frequency of adverse drug reactions was similar to the safety profile observed in patients with RA, PsA and AS.
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of golimumab. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to golimumab exposure.
- Immune System Disorders: Serious systemic hypersensitivity reactions (including anaphylactic reaction), sarcoidosis
- Neoplasms benign, malignant and unspecified: Melanoma
- Respiratory, thoracic and mediastinal disorders: Interstitial lung disease
- Skin and subcutaneous tissue disorders: Skin exfoliation, rash, bullous skin reactions
Drug Interactions
Methotrexate
For the treatment of RA, golimumab should be used with methotrexate (MTX). Since the presence or absence of concomitant MTX did not appear to influence the efficacy or safety of golimumab in the treatment of PsA or AS, golimumab can be used with or without MTX in the treatment of PsA and AS.
Biological Products for RA, PsA, and/or AS
An increased risk of serious infections has been seen in clinical RA trials of other TNF-blockers used in combination with anakinra or abatacept, with no added benefit; therefore, use of golimumab with abatacept or anakinra is not recommended. A higher rate of serious infections has also been observed in RA patients treated with rituximab who received subsequent treatment with a TNF-blocker. The concomitant use of golimumab with biologics approved to treat RA, PsA, or AS is not recommended because of the possibility of an increased risk of infection.
Live Vaccines/Therapeutic Infectious Agents
Live vaccines should not be given concurrently with golimumab. Therapeutic infectious agents should not be given concurrently with golimumab. Infants born to women treated with golimumab during their pregnancy may be at increased risk of infection for up to 6 months. Administration of live vaccines to infants exposed to golimumab in utero is not recommended for 6 months following the mother's last golimumab injection during pregnancy.
Cytochrome P450 Substrates
The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (e.g., TNFα) during chronic inflammation. Therefore, it is expected that for a molecule that antagonizes cytokine activity, such as golimumab, the formation of CYP450 enzymes could be normalized. Upon initiation or discontinuation of golimumab in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): B There are no adequate and well-controlled trials of golimumab in pregnant women. Because animal reproduction and developmental studies are not always predictive of human response, it is not known whether golimumab can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. golimumab should be used during pregnancy only if clearly needed.
An embryofetal developmental toxicology study was performed in which pregnant cynomolgus monkeys were treated subcutaneously with golimumab during the first trimester with doses up to 50 mg/kg twice weekly (360 times greater than the maximum recommended human dose-MRHD) and has revealed no evidence of harm to maternal animals or fetuses. Umbilical cord blood samples collected at the end of the second trimester showed that fetuses were exposed to golimumab during gestation. In this study, in utero exposure to golimumab produced no developmental defects to the fetus.
A pre- and post-natal developmental study was performed in which pregnant cynomolgus monkeys were treated with golimumab during the second and third trimesters, and during lactation at doses up to 50 mg/kg twice weekly (860 times and 310 times greater than the maximal steady state human blood levels for maternal animals and neonates, respectively) and has revealed no evidence of harm to maternal animals or neonates. Golimumab was present in the neonatal serum from the time of birth and for up to six months postpartum. Exposure to golimumab during gestation and during the postnatal period caused no developmental defects in the infants.
IgG antibodies are known to cross the placenta during pregnancy and have been detected in the serum of infants born to patients treated with these antibodies. Since golimumab is an IgG antibody, infants born to women treated with golimumab during their pregnancy may be at increased risk of infection for up to 6 months. Administration of live vaccines to infants exposed to golimumab in utero is not recommended for 6 months following the mother's last golimumab injection during pregnancy.
Pregnancy Category (AUS): C
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Golimumab in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Golimumab during labor and delivery.
Nursing Mothers
It is not known whether golimumab is excreted in human milk or absorbed systemically after ingestion. Because many drugs and immunoglobulins are excreted in human milk, and because of the potential for adverse reactions in nursing infants from golimumab, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
In the pre- and post-natal development study in cynomolgus monkeys in which golimumab was administered subcutaneously during pregnancy and lactation, golimumab was detected in the breast milk at concentrations that were approximately 400-fold lower than the maternal serum concentrations.
Pediatric Use
Safety and effectiveness of golimumab in pediatric patients less than 18 years of age have not been established.
Geriatic Use
In the Phase 3 trials in RA, PsA, and AS, there were no overall differences in SAEs, serious infections, and AEs in golimumab-treated patients ages 65 or older (N = 155) compared with younger golimumab-treated patients. In UC, there were insufficient numbers of patients aged 65 and over to determine whether they respond differently from patients aged 18 to 65. Because there is a higher incidence of infections in the geriatric population in general, caution should be used in treating geriatric patients with golimumab.
Gender
Population PK analyses suggested no PK differences between male and female patients after body weight adjustment in the RA, PsA and UC trials. In the AS trial, female patients showed 13% higher apparent clearance than male patients after body weight adjustment. Subgroup analysis based on gender showed that both female and male patients achieved clinically significant response at the proposed clinical dose. Dosage adjustment based on gender is not needed.
Race
No ethnicity-related PK differences were observed between Caucasians and Asians, and there were too few patients of other races to assess for PK differences.
Renal Impairment
No formal trial of the effect of renal impairment on the PK of golimumab was conducted.
Hepatic Impairment
No formal trial of the effect of hepatic impairment on the PK of golimumab was conducted.
Females of Reproductive Potential and Males
A fertility study conducted in mice using an analogous anti-mouse TNFα antibody showed no impairment of fertility.
Immunocompromised Patients
There is no FDA guidance one the use of Golimumab in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Golimumab Administration in the drug label.
Monitoring
Closely monitor patients for the development of signs and symptoms of infection during and after treatment with golimumab. Discontinue golimumab if a patient develops a serious infection, an opportunistic infection, or sepsis. For a patient who develops a new infection during treatment with golimumab, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, initiate appropriate antimicrobial therapy and closely monitor them.
IV Compatibility
There is limited information regarding the compatibility of Golimumab and IV administrations.
Overdosage
In a clinical trial, 5 patients received protocol-directed single infusions of 10 mg/kg of intravenous golimumab without serious adverse reactions or other significant reactions. The highest weight patient was 100 kg, and therefore received a single intravenous infusion of 1000 mg of golimumab. There were no golimumab overdoses in the clinical trials.
Pharmacology
Mechanism of Action
Golimumab is a human monoclonal antibody that binds to both the soluble and transmembrane bioactive forms of human TNFα. This interaction prevents the binding of TNFα to its receptors, thereby inhibiting the biological activity of TNFα (a cytokine protein). There was no evidence of the golimumab antibody binding to other TNF superfamily ligands; in particular, the golimumab antibody did not bind or neutralize human lymphotoxin. Golimumab did not lyse human monocytes expressing transmembrane TNF in the presence of complement or effector cells.
Elevated TNFα levels in the blood, synovium, and joints have been implicated in the pathophysiology of several chronic inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. TNFα is an important mediator of the articular inflammation that is characteristic of these diseases. The exact mechanism by which golimumab treats ulcerative colitis is unknown. Golimumab modulated the in vitro biological effects mediated by TNF in several bioassays, including the expression of adhesion proteins responsible for leukocyte infiltration (E-selectin, ICAM-1 and VCAM-1) and the secretion of proinflammatory cytokines (IL-6, IL-8, G-CSF and GM-CSF).
Structure
There is limited information regarding Golimumab Structure in the drug label.
Pharmacodynamics
In clinical trials, decreases in C-reactive protein (CRP), interleukin (IL)-6, matrix metalloproteinase 3 (MMP-3), intercellular adhesion molecule (ICAM)-1 and vascular endothelial growth factor (VEGF) were observed following golimumab administration in patients with RA, PsA, and AS.
Pharmacokinetics
Absorption
Following subcutaneous administration of golimumab to healthy subjects and patients with active RA, the median time to reach maximum serum concentrations (Tmax) ranged from 2 to 6 days. A subcutaneous injection of 50 mg golimumab to healthy subjects produced a mean ± standard deviation maximum serum concentration (Cmax) of 3.2 ± 1.4 µg/mL.
By cross-trial comparisons of mean AUCinf values following an IV or subcutaneous administration of golimumab, the absolute bioavailability of subcutaneous golimumab was estimated to be approximately 53%.
Distribution
Following a single IV administration over the dose range of 0.1 to 10.0 mg/kg in patients with active RA, mean volume of distribution ranged from 58 to 126 mL/kg. The volume of distribution for golimumab indicates that golimumab is distributed primarily in the circulatory system with limited extravascular distribution.
Metabolism
The exact metabolic pathway of golimumab is unknown.
Elimination
Following a single IV administration over the dose range of 0.1 to 10.0 mg/kg in patients with active RA, mean systemic clearance of golimumab was estimated to be 4.9 to 6.7 mL/day/kg.
Median terminal half-life values were estimated to be approximately 2 weeks in healthy subjects and patients with active RA, PsA or AS.
Population PK analyses indicated that concomitant use of NSAIDs, oral corticosteroids, or sulfasalazine did not influence the apparent clearance of golimumab.
Patients who developed anti-golimumab antibodies generally had lower steady-state serum trough concentrations of golimumab.
Dose linearity
golimumab exhibited dose-proportional pharmacokinetics (PK) in patients with active RA over the dose range of 0.1 to 10 mg/kg following a single intravenous (IV) dose. Following a single SC dose in healthy subjects, dose proportional pharmacokinetics were also observed over a dose range of 50 mg to 400 mg.
Single dose versus multiple doses
When 50 mg golimumab was administered subcutaneous to patients with RA, PsA, or AS every 4 weeks, serum concentrations appeared to reach steady state by Week 12. With concomitant use of methotrexate (MTX), treatment with 50 mg golimumab subcutaneous every 4 weeks resulted in a mean steady-state trough serum concentration of approximately 0.4–0.6 µg/mL in patients with active RA, approximately 0.5 µg/mL in patients with active PsA, and approximately 0.8 µg/mL in patients with active AS. Patients with RA, PsA, and AS treated with golimumab 50 mg and MTX had approximately 52%, 36% and 21% higher mean steady-state trough concentrations of golimumab, respectively compared with those treated with golimumab 50 mg without MTX. The presence of MTX also decreased anti-golimumab antibody incidence from 7% to 2% For RA, golimumab should be used with MTX. In the PsA and AS trials, the presence or absence of concomitant MTX did not appear to influence clinical efficacy and safety parameters.
When induction doses of 200 mg and 100 mg golimumab at week 0 and 2, respectively, followed by maintenance doses of 100 mg golimumab every 4 weeks were administered subcutaneously in patients with UC, serum golimumab concentrations reached steady state by week 8 after the first maintenance dose. Treatment with 100 mg golimumab subcutaneous every 4 weeks during maintenance resulted in a mean steady-state trough serum concentration of approximately 1.8 ± 1.1 µg/mL.
Effect of weight on pharmacokinetics
Population PK analyses showed there was a trend toward higher apparent clearance of golimumab with increasing weight. Treatment with the recommended maintenance dose regimen of golimumab 100 mg in UC patients did not result in meaningful differences in clinical efficacy among different weight groups. Across the PsA and AS populations, no meaningful differences in clinical efficacy were observed among the subgroups by weight quartile. The RA trial in MTX-experienced and TNF-blocker-naïve patients (Trial RA-2) did show evidence of a reduction in clinical efficacy with increasing body weight, but this effect was observed for both tested doses of golimumab (50 mg and 100 mg). There is no need to adjust the dosage of golimumab based on a patient's weight.
Nonclinical Toxicology
Carcinogenesis and Mutagenesis
Long-term animal studies of golimumab have not been conducted to evaluate its carcinogenic potential. Mutagenicity studies have not been conducted with golimumab.
Clinical Studies
Rheumatoid Arthritis
The efficacy and safety of golimumab were evaluated in 3 multicenter, randomized, double-blind, controlled trials (Trials RA-1, RA-2, and RA-3) in 1542 patients ≥ 18 years of age with moderately to severely active RA, diagnosed according to the American College of Rheumatology (ACR) criteria, for at least 3 months prior to administration of trial agent. Patients were required to have at least 4 swollen and 4 tender joints. golimumab was administered subcutaneously at doses of 50 mg or 100 mg every 4 weeks. Double-blinded controlled efficacy data were collected and analyzed through Week 24. Patients were allowed to continue stable doses of concomitant low dose corticosteroids (equivalent to ≤ 10 mg of prednisone a day) and/or NSAIDs and patients may have received oral MTX during the trials.
Trial RA-1 evaluated 445 patients who were previously treated (at least 8 to 12 weeks prior to administration of trial agent) with one or more doses of a biologic TNF-blocker without a serious adverse reaction. Patients may have discontinued the biologic TNF-blocker for a variety of reasons. Patients were randomized to receive placebo (n = 150), golimumab 50 mg (n = 147), or golimumab 100 mg (n = 148). Patients were allowed to continue stable doses of concomitant MTX, sulfasalazine (SSZ), and/or hydroxychloroquine (HCQ) during the trial. The use of other DMARDs including cytotoxic agents or other biologics was prohibited.
Trial RA-2 evaluated 444 patients who had active RA despite a stable dose of at least 15 mg/week of MTX and who had not been previously treated with a biologic TNF-blocker. Patients were randomized to receive background MTX (n = 133), golimumab 50 mg + background MTX (n = 89), golimumab 100 mg + background MTX (n = 89), or golimumab 100 mg monotherapy (n = 133). The use of other DMARDs including SSZ, HCQ, cytotoxic agents, or other biologics was prohibited.
Trial RA-3 evaluated 637 patients with active RA who were MTX-naïve and had not previously been treated with a biologic TNF-blocker. Patients were randomized to receive MTX (n = 160), golimumab 50 mg + MTX (n = 159), golimumab 100 mg + MTX (n = 159), or golimumab 100 mg monotherapy (n = 159). For patients receiving MTX, MTX was administered at a dose of 10 mg/week beginning at Week 0 and increased to 20 mg/week by Week 8. The use of other DMARDs including SSZ, HCQ, cytotoxic agents, or other biologics was prohibited.
The primary endpoint in Trial RA-1 and Trial RA-2 was the percentage of patients achieving an ACR 20 response at Week 14 and the primary endpoint in Trial RA-3 was the percentage of patients achieving an ACR 50 response at Week 24.
In Trials RA-1, RA-2, and RA-3, the median duration of RA disease was 9.4, 5.7, and 1.2 years; and 99%, 75%, and 54% of the patients used at least one DMARD in the past, respectively. Approximately 77% and 57% of patients received concomitant NSAIDs and low dose corticosteroids, respectively, in the 3 pooled RA trials.
Clinical Response
In the 3 RA trials, a greater percentage of patients treated with the combination of golimumab and MTX achieved ACR responses at Week 14 (Trials RA-1 and RA-2) and Week 24 (Studies RA-1, RA-2, and RA-3) versus patients treated with the MTX alone. There was no clear evidence of improved ACR response with the higher golimumab dose group (100 mg) compared to the lower golimumab dose group (50 mg). In Trials RA-2 and RA-3, the golimumab monotherapy groups were not statistically different from the MTX monotherapy groups in ACR responses. Table 2 shows the proportion of patients with the ACR response for the golimumab 50 mg and control groups in Trials RA-1, RA-2, and RA-3. In the subset of patients who received golimumab in combination with MTX in Trial RA-1, the proportion of patients achieving ACR 20, 50 and 70 responses at week 14 were 40%, 18%, and 12%, respectively, in the golimumab 50 mg + MTX group (N = 101) compared with 17%, 6%, and 2%, respectively, in the placebo + MTX group (N = 103). Table 3 shows the percent improvement in the components of the ACR response criteria for the golimumab 50 mg + MTX and MTX groups in Trial RA-2. The percent of patients achieving ACR 20 responses by visit for Trial RA-2 is shown in Figure 1. ACR 20 responses were observed in 38% of patients in the golimumab 50 mg + MTX group at the first assessment (Week 4) after the initial golimumab administration.
Physical Function Response in Patients with RA
In Trials RA-1 and RA-2, the golimumab 50 mg groups demonstrated a greater improvement compared to the control groups in the change in mean Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline to Week 24: 0.23 vs. 0.03 in RA-1, 0.47 vs. 0.13 in RA-2, respectively. Also in Trials RA-1 and RA-2, the golimumab 50 mg groups compared to the control groups had a greater proportion of HAQ responders (change from baseline > 0.22) at Week 24: 43% vs. 27%, 65% vs. 35%, respectively.
Psoriatic Arthritis
The safety and efficacy of golimumab were evaluated in a multi-center, randomized, double-blind, placebo-controlled trial in 405 adult patients with moderately to severely active PsA (≥ 3 swollen joints and ≥ 3 tender joints) despite NSAID or DMARD therapy (Trial PsA). Patients in this trial had a diagnosis of PsA for at least 6 months with a qualifying psoriatic skin lesion of at least 2 cm in diameter. Previous treatment with a biologic TNF-blocker was not allowed. Patients were randomly assigned to placebo (n = 113), golimumab 50 mg (n = 146), or golimumab 100 mg (n = 146) given subcutaneously every 4 weeks. Patients were allowed to receive stable doses of concomitant MTX (≤ 25 mg/week), low dose oral corticosteroids (equivalent to ≤ 10 mg of prednisone a day), and/or NSAIDs during the trial. The use of other DMARDs including SSZ, HCQ, cytotoxic agents, or other biologics was prohibited. The primary endpoint was the percentage of patients achieving ACR 20 response at Week 14. Placebo-controlled efficacy data were collected and analyzed through Week 24.
Patients with each subtype of PsA were enrolled, including polyarticular arthritis with no rheumatoid nodules (43%), asymmetric peripheral arthritis (30%), distal interphalangeal (DIP) joint arthritis (15%), spondylitis with peripheral arthritis (11%), and arthritis mutilans (1%). The median duration of PsA disease was 5.1 years, 78% of patients received at least one DMARD in the past, and approximately 48% of patients received MTX, and 16% received low dose oral steroids.
Clinical Response in Patients with PsA
golimumab ± MTX, compared with placebo ± MTX, resulted in significant improvement in signs and symptoms as demonstrated by the proportion of patients with an ACR 20 response at Week 14 in Trial PsA (see TABLE 4). There was no clear evidence of improved ACR response with the higher golimumab dose group (100 mg) compared to the lower golimumab dose group (50 mg). ACR responses observed in the golimumab-treated groups were similar in patients receiving and not receiving concomitant MTX. Similar ACR 20 responses at Week 14 were observed in patients with different PsA subtypes. However, the number of patients with arthritis mutilans was too small to allow meaningful assessment. golimumab 50 mg treatment also resulted in significantly greater improvement compared with placebo for each ACR component in Trial PsA (Table 5). Treatment with golimumab resulted in improvement in enthesitis and skin manifestations in patients with PsA. However, the safety and efficacy of golimumab in the treatment of patients with plaque psoriasis has not been established.
The percent of patients achieving ACR 20 responses by visit for Trial PsA is shown in Figure 2. ACR 20 responses were observed in 31% of patients in the golimumab 50 mg + MTX group at the first assessment (Week 4) after the initial golimumab administration.
Physical Function Response in Patients with PsA
In Trial PsA, golimumab 50 mg demonstrated a greater improvement compared to placebo in the change in mean Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline to Week 24 (0.33 and -0.01, respectively). In addition, the golimumab 50 mg group compared to the placebo group had a greater proportion of HAQ responders (≥ 0.3 change from baseline) at Week 24: 43% vs. 22%, respectively.
Ankylosing Spondylitis
The safety and efficacy of golimumab were evaluated in a multi-center, randomized, double-blind, placebo-controlled trial in 356 adult patients with active ankylosing spondylitis according to modified New York criteria for at least 3 months (Trial AS). Patients had symptoms of active disease [defined as a Bath AS Disease Activity Index (BASDAI) ≥ 4 and VAS for total back pain of ≥ 4, on scales of 0 to 10 cm] despite current or previous NSAID therapy. Patients were excluded if they were previously treated with a biologic TNF-blocker or if they had complete ankylosis of the spine. Patients were randomly assigned to placebo (n = 78), golimumab 50 mg (n = 138), or golimumab 100 mg (n = 140) administered subcutaneously every 4 weeks. Patients were allowed to continue stable doses of concomitant MTX, sulfasalazine (SSZ), hydroxychloroquine (HCQ), low dose corticosteroids (equivalent to < 10 mg of prednisone a day), and/or NSAIDs during the trial. The use of other DMARDs including cytotoxic agents or other biologics was prohibited.
The primary endpoint was the percentage of patients achieving an ASsessment in Ankylosing Spondylitis (ASAS) 20 response at Week 14. Placebo-controlled efficacy data were collected and analyzed through Week 24.
In Trial AS, the median duration of AS disease was 5.6 years, median duration of inflammatory back pain was 12 years, 83% were HLA-B27 positive, 24% had prior joint surgery or procedure, and 55% received at least one DMARD in the past. During the trial, the use of concomitant DMARDs and/or NSAIDs was as follows: MTX (20%), SSZ (26%), HCQ (1%), low dose oral steroids (16%), and NSAIDs (90%).
Clinical Response in Patients with AS
In Trial AS, golimumab ± DMARDs treatment, compared with placebo ± DMARDs, resulted in a significant improvement in signs and symptoms as demonstrated by the proportion of patients with an ASAS 20 response at Week 14 (see TABLE 6). There was no clear evidence of improved ASAS response with the higher golimumab dose group (100 mg) compared to the lower golimumab dose group (50 mg). Table 7 shows the percent improvement in the components of the ASAS response criteria for the golimumab 50 mg ± DMARDs and placebo ± DMARDs groups in Trial AS.
The percent of patients achieving ASAS 20 responses by visit for Trial AS is shown in Figure 3. ASAS 20 responses were observed in 48% of patients in the golimumab 50 mg + MTX group at the first assessment (Week 4) after the initial golimumab administration.
Ulcerative Colitis
The safety and efficacy of golimumab were evaluated in two multi-center, randomized, double-blind, placebo-controlled clinical trials in patients ≥ 18 years of age (Trials UC-1 and UC-2).
Trial UC-1 was an induction trial conducted in patients with moderately to severely active ulcerative colitis (UC), defined as a Mayo score of 6 to 12 [the Mayo score ranges from 0 to 12 and has four subscales that are each scored from 0 (normal) to 3 (most severe): stool frequency, rectal bleeding, findings on endoscopy, and physician global assessment]. At baseline, subjects also had an endoscopy subscore of 2 or 3 on a 3-point scale (an endoscopy score of 2 is defined by marked erythema, absent vascular pattern, friability, erosions; and a score of 3 is defined by spontaneous bleeding, ulceration). Patients were corticosteroid dependent (i.e., an inability to successfully taper corticosteroids without a return of the symptoms of UC) or had an inadequate response to or had failed to tolerate at least one of the following therapies: oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine.
Trial UC-1 was divided into 2 parts. In Part 1 (dose finding), patients were randomized to one of 4 treatment groups: 400 mg golimumab administered subcutaneously (SC) at Week 0 and 200 mg at Week 2 (400/200 mg), 200 mg golimumab SC at Week 0 and 100 mg at Week 2 (200/100 mg), 100 mg golimumab SC at Week 0 and 50 mg at Week 2 (100/50 mg), or placebo SC at Weeks 0 and 2. In Part 2 (dose confirming), efficacy was evaluated in 761 patients who were randomized to receive either 400 mg golimumab SC at Week 0 and 200 mg at Week 2, 200 mg golimumab SC at Week 0 and 100 mg at Week 2, or placebo SC at Weeks 0 and 2. golimumab 100/50 mg SC was not evaluated in Part 2; its safety and effectiveness has not been established in UC. Concomitant stable doses of oral aminosalicylates (5-ASA), oral corticosteroids (less than 40 mg/day), azathioprine (AZA), 6-mercaptopurine (6-MP), and/or methotrexate (MTX) were permitted. Patients who received previous TNF inhibitors were excluded. The primary endpoint was the percent of patients in clinical response at Week 6, defined as a decrease from baseline in the Mayo score by ≥ 30% and ≥ 3 points, accompanied by a decrease in the rectal bleeding subscore of ≥ 1 or a rectal bleeding subscore of 0 (no blood seen) or 1 (streaks of blood with stool less than half the time).
Trial UC-2 was a randomized-withdrawal maintenance trial that evaluated 456 patients who achieved clinical response with golimumab induction and tolerated golimumab treatment. Patients were randomized to receive golimumab 50 mg, golimumab 100 mg or placebo administered subcutaneously every 4 weeks. Concomitant stable doses of oral aminosalicylates, azathioprine, 6-mercaptopurine, and/or methotrexate were permitted. Corticosteroids were to be tapered at the start of the maintenance trial. The primary endpoint was the percent of patients maintaining clinical response through Week 54.
Clinical Response, Clinical Remission and Improvement of Endoscopic Appearance of the Mucosa
In Trial UC-1, a greater proportion of patients achieved clinical response, clinical remission and had improvement of endoscopic appearance of the mucosa at Week 6 in the golimumab 200/100 mg group compared with the placebo group. The golimumab 400/200 mg group did not demonstrate additional clinical benefit over the golimumab 200/100 mg group. Clinical response was defined as a decrease from baseline in the Mayo score of ≥ 30% and ≥ 3 points, accompanied by a decrease in the rectal bleeding subscore of ≥ 1 or a rectal bleeding subscore of 0 or 1. Clinical remission was defined as a Mayo score ≤ 2 points, with no individual subscore > 1. Improvement of endoscopic appearance of the mucosa was defined as a Mayo endoscopy subscore of 0 (normal or inactive disease) or 1 (erythema, decreased vascular pattern, mild friability).
In Trial UC-2, a greater proportion of patients maintained clinical response through Week 54 in the golimumab 100 mg group compared with the placebo group. In Trial UC-2, golimumab-treated patients in clinical response (which included the subset of patients in clinical remission) in Trial UC-1, were again assessed for clinical remission at Week 30 and Week 54. A greater proportion of patients had clinical remission at both Weeks 30 and 54 without demonstrating a loss of response at any time point through Week 54 in the golimumab 100 mg group compared with the placebo group.
How Supplied
Golimumab for injection:
- 50 mg/0.5 mL in a single dose
- 100 mg/1 mL in a single dose
Storage
Stored at 2°C to 8°C (36°F to 46°F)
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Patients should be advised of the potential benefits and risks of golimumab. Physicians should instruct their patients to read the Medication Guide before starting golimumab therapy and to read it each time the prescription is renewed.
Infections
Inform patients that golimumab may lower the ability of their immune system to fight infections. Instruct the patient of the importance of contacting their doctor if they develop any symptoms of infection, including tuberculosis, invasive fungal infections, and hepatitis B reactivation.
Malignancies
Patients should be counseled about the risk of lymphoma and other malignancies while receiving golimumab.
Allergic Reactions
Advise latex-sensitive patients that the needle cover on the prefilled syringe as well as the prefilled syringe in the prefilled SmartJect autoinjector contains dry natural rubber (a derivative of latex).
Other Medical Conditions
Advise patients to report any signs of new or worsening medical conditions such as congestive heart failure, demyelinating disorders, autoimmune diseases, liver disease, cytopenias, or psoriasis.
Instructions for Safe Administration
The first self-injection should be performed under the supervision of a qualified healthcare professional. If a patient or caregiver is to administer golimumab, he/she should be instructed in injection techniques and their ability to inject subcutaneously should be assessed to ensure the proper administration of golimumab
Advise the patient to read the FDA-approved Instructions for Use and provide the following instructions to patients:
- Prior to use, remove the prefilled syringe or the prefilled SmartJect autoinjector from the refrigerator and allow golimumab to sit at room temperature outside of the carton for 30 minutes and out of the reach of children.
- Do not warm golimumab in any other way. For example, do not warm golimumab in a microwave or in hot water.
- Do not remove the prefilled syringe needle cover or SmartJect autoinjector cap while allowing golimumab to reach room temperature. Remove these immediately before injection.
- Do not pull the autoinjector away from the skin until you hear a first "click" sound and then a second "click" sound (the injection is finished and the needle is pulled back). It usually takes about 3 to 6 seconds but may take up to 15 seconds for you to hear the second "click" after the first "click". If the autoinjector is pulled away from the skin before the injection is completed, a full dose of golimumab may not be administered.
- A puncture-resistant container for disposal of needles and syringes should be used. Patients or caregivers should be instructed in the technique of proper syringe and needle disposal, and be advised not to reuse these items.
Precautions with Alcohol
Alcohol-Golimumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
- Simponi [1]
- Simponi Aria
Look-Alike Drug Names
There is limited information regarding Golimumab Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
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