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==Overview==
==Overview==
There is no known cure for rheumatoid arthritis. However, many different types of treatment can be used to alleviate symptoms and/or to modify the disease process.
The mainstay of treatment of [[rheumatoid arthritis]] is pharmacotherapy. Early diagnosis of [[rheumatoid arthritis]] is helpful in treatment. Choice of treatment depends on various factors such as stage of [[disease]], comorbid conditions, stage of therapy and presence of severe prognostic signs. There are two types of therapies- non-pharmacological therapy and pharmacological therapy. There are different drug regimen depending upon the stage of the disease. In active stage, combined therapy include disease-modifying antirheumatic drugs ([[DMARDs]]) are used along with the [[Anti-inflammatory drug|anti-inflammatory drugs]]. Therapy for resistant disease and flares is the addition of oral [[glucocorticoids]]. In case of the flare, add another [[DMARDs]] with [[methotrexate]] or replace with another [[DMARDs]].


==Medical Therapy==
==Medical Therapy==
The mainstay of treatment of [[rheumatoid arthritis]] is pharmacotherapy.
Early diagnosis of [[rheumatoid arthritis]] is helpful in treatment.
Early diagnosis of [[rheumatoid arthritis]] is helpful in treatment.
*Choice of treatment depends upon the following factors:
**Stage of disease (eg, mild/moderate/severe).
**Associated with other comorbid conditions.
**Stage of therapy (eg, initial versus subsequent therapy in patients resistant to treatment).
**Presence of severe prognostic signs


Choice of treatment depends on the following factors:
*Stage of [[disease]] (eg, mild/moderate/severe).
*Associated with other [[comorbid]] conditions.
*Stage of [[therapy]] (eg, initial versus subsequent therapy in patients resistant to treatment).
*Presence of severe [[prognostic]] signs.
'''Non-pharmacological treatment'''
*Heat or [[cold]] compresses are used to reduce the [[swelling]], [[pain]], and [[stiffness]].
*[[Orthotics]] and splints.
*Active and passive [[exercise]] helps in restoring range of motion.
*Patient [[education]] about taking healthy [[diet]] and taking proper rest.
'''Pharmacological treatment'''
*The mainstay of treatment of [[rheumatoid arthritis]] is [[pharmacotherapy]].
*Principles used for the treatment of [[rheumatoid arthritis]] are:
**Making an early [[diagnosis]] and taking early treatment is helpful.
**Use of disease-modifying antirheumatic drugs early in the treatment.
**Consult a specialist like a [[rheumatologist]].
**Use of [[anti-inflammatory]] drugs and [[glucocorticoids]] as an adjuvant.
'''Test to be done before starting the therapy '''
*[[CBC]] with differentials.
*[[ESR]] and [[CRP]]
*Serum [[creatinine]]
*Screen for [[Hepatitis B]] and [[Hepatitis C]]
*Test for latent [[tuberculosis]]
*[[Ophthalmological]] testing


===Disease Name===
'''Various disease-modifying antirheumatic drugs (DMARDs) used are''':


* '''1 Stage 1 - Name of stage'''
1)[[Leflunomide]]:
** 1.1 '''Specific Organ system involved 1'''
*Preferred regimen: Loading dose is 100 mg PO q24h for 3 days, the maintenance dose is 20 mg  q24h '''(Contraindications in pregnancy)'''  
*** 1.1.1 '''Adult'''
2)[[Sulfasalazine]]:
**** Preferred regimen (1): [[drug name]] 100 mg PO q12h for 10-21 days '''(Contraindications/specific instructions)'''  
*Preferred regimen: Initial dose: 500 mg PO q24h, the maintenance dose is 2 g PO once in 7days  
**** Preferred regimen (2): [[drug name]] 500 mg PO q8h for 14-21 days
3)[[Hydroxychloroquine]]:
**** Preferred regimen (3): [[drug name]] 500 mg q12h for 14-21 days
*Preferred regimen: Initial dose: 400 mg PO q24h x 3months, the maintenance dose is 300 mg PO q24h '''(Special instructions an eye examination is required before starting the therapy)'''
**** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days  
4)[[Rituximab]]:
**** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
*Preferred regimen:1000 mg IV 2 doses given 2 weeks apart, in combination with [[Methotrexate|MTX]]
**** Alternative regimen (3): [[drug name]] 500 mg PO q6h for 14–21 days
5)[[Tocilizumab]]:
*** 1.1.2 '''Pediatric'''
*Preferred regimen: 4mg/kg once every 4 weeks
**** 1.1.2.1 (Specific population e.g. '''children < 8 years of age''')
6)[[Azathioprine]]:
***** Preferred regimen (1): [[drug name]] 50 mg/kg PO per day q8h (maximum, 500 mg per dose)
* Preferred regimen: Initial dose 1mg/kg PO q24h for 6 to 8 weeks, the maintenance dose is reduction of dose 0.5mg/kg every week for 4 weeks
***** Preferred regimen (2): [[drug name]] 30 mg/kg PO per day in 2 divided doses (maximum, 500 mg per dose)
7) [[Cyclosporine|Cyclosporin]]:
***** Alternative regimen (1): [[drug name]]10 mg/kg PO q6h (maximum, 500 mg per day)
*Preferred regimen: 2.5mg/kg PO q12h for 8 weeks
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
*It is used in patients who are unresponsive to [[methotrexate]]
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
8) [[Anakinra]]
****1.1.2.2 (Specific population e.g. ''''''children < 8 years of age'''''')
*Preferred regimen: 100 mg SC q24h
***** Preferred regimen (1): [[drug name]] 4 mg/kg/day PO q12h（maximum, 100 mg per dose）
*This is used for slowing the progression of moderately to severely active [[Rheumatoid arthritis|RA]]
***** Alternative regimen (1): [[drug name]] 10 mg/kg PO q6h (maximum, 500 mg per day)
9) [[Abatacept]]:
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose) 
*Preferred regimen: dose is according to body weight such as <60kg -500mg, 60 to 100kg- 750mg and  more than 100kg is 1000mg IV followed by same dose at 2 weeks, 4 weeks, and every 4 weeks afterwards
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
*This is used for moderately to severely active RA.
** 1.2 '''Specific Organ system involved 2'''
10) [[Baricitinib]]:
*** 1.2.1 '''Adult'''
*The recommended dose of baricitinib is 2 mg once daily
**** Preferred regimen (1): [[drug name]] 500 mg PO q8h
*FDA approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies<br>
*** 1.2.2  '''Pediatric'''
**** Preferred regimen (1): [[drug name]] 50 mg/kg/day PO q8h (maximum, 500 mg per dose)


* 2 '''Stage 2 - Name of stage'''
'''DMARDs and TNF Inhibitors:'''
** 2.1 '''Specific Organ system involved 1 '''
 
**: '''Note (1):'''  
1)[[Infliximab]]:
**: '''Note (2)''':
*This is the [[Monoclonal antibody|monoclonal]] [[antibody]] against TNF-α
**: '''Note (3):'''
* Preferred regimen: 3 mg/kg IV at weeks 0, 2, and 6 and then every 4-8 weeks, usually with [[MTX]]
*** 2.1.1 '''Adult'''
2)[[Etanercept]]:
**** Parenteral regimen
*This is a bivalent p75–[[TNF]] receptor attached to the Fc portion of IgG human antibody
***** Preferred regimen (1): [[drug name]] 2 g IV q24h for 14 (14–21) days
*Preferred regimen: 25 mg SC 2 times weekly or 50 mg SC once weekly, with or without concomitant MTX
***** Alternative regimen (1): [[drug name]] 2 g IV q8h for 14 (14–21) days
3)[[Golimumab]]:
***** Alternative regimen (2): [[drug name]] 18–24 MU/day IV q4h for 14 (14–21) days
*This is a human monoclonal antibody to TNF-α which inhibits TNF-α bioactivity
**** Oral regimen
*Preferred regimen: 50 mg SC once every month
***** Preferred regimen (1): [[drug name]] 500 mg PO q8h for 14 (14–21) days
4)[[Certolizumab]]:
***** Preferred regimen (2): [[drug name]] 100 mg PO q12h for 14 (14–21) days
*This is a pegylated anti−TNF-α agent
***** Preferred regimen (3): [[drug name]] 500 mg PO q12h for 14 (14–21) days
*Preferred regimen: First dose of 400 mg SC followed by 2 doses of 400 mg SC at 2nd and 4th week, followed by 200 mg every other week
***** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days  
5)[[Adalimumab]]:
***** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
*This is the recombinant human IgG1 monoclonal antibody and it binds to TNF-α and blocks interaction with p55 and p75 cell-surface TNF receptors
***** Alternative regimen (3):[[drug name]] 500 mg PO q6h for 14–21 days
*Preferred regimen: 40mg SC every other week. No clear benefit of 80 mg every other week<ref name="pmid12379628">{{cite journal| author=Rau R| title=Adalimumab (a fully human anti-tumour necrosis factor alpha monoclonal antibody) in the treatment of active rheumatoid arthritis: the initial results of five trials. | journal=Ann Rheum Dis | year= 2002 | volume= 61 Suppl 2 | issue= Suppl 2 | pages= ii70-3 | pmid=12379628 | doi=10.1136/ard.61.suppl_2.ii70 | pmc=1766697 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12379628 }} </ref>.
*** 2.1.2 '''Pediatric'''
 
**** Parenteral regimen
'''Different drug regimen depending upon the stage of disease''':
***** Preferred regimen (1): [[drug name]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
 
***** Alternative regimen (1): [[drug name]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
'''Active disease''':<ref name="pmid18635256">{{cite journal |vauthors=Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D, Singh A, Pedersen RD, Koenig AS, Freundlich B |title=Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial |journal=Lancet |volume=372 |issue=9636 |pages=375–82 |date=August 2008 |pmid=18635256 |doi=10.1016/S0140-6736(08)61000-4 |url=}}</ref><ref name="pmid29073913">{{cite journal |vauthors=Darzi A, Harfouche M, Arayssi T, Alemadi S, Alnaqbi KA, Badsha H, Al Balushi F, Elzorkany B, Halabi H, Hamoudeh M, Hazer W, Masri B, Omair MA, Uthman I, Ziade N, Singh JA, Christiansen R, Tugwell P, Schünemann HJ, Akl EA |title=Correction to: Adaptation of the 2015 American College of Rheumatology treatment guideline for rheumatoid arthritis for the Eastern Mediterranean Region: an exemplar of the GRADE Adolopment |journal=Health Qual Life Outcomes |volume=15 |issue=1 |pages=214 |date=October 2017 |pmid=29073913 |pmc=5658904 |doi=10.1186/s12955-017-0791-9 |url=}}</ref>
***** Alternative regimen (2):  [[drug name]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day) ''''''(Contraindications/specific instructions)''''''
*Combined therapy include disease-modifying antirheumatic drugs ([[DMARDs]]) are used along with the anti-inflammatory drugs.
**** Oral regimen
*The first line of the drug is [[methotrexate]] along with anti-inflammatory drugs like [[NSAIDs]] and [[glucocorticoids]].
***** Preferred regimen (1): [[drug name]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
*Preferred regimen : [[Methotrexate]] 7.5 mg PO weekly for 4 weeks.
***** Preferred regimen (2): [[drug name]] '''(for children aged ≥ 8 years)''' 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
*Followed by an increase in dose by 2.5mg PO or 5mg PO depending on the severity of disease and [[renal function]]. 
***** Preferred regimen (3): [[drug name]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
*Monitoring of renal function is done after 4 weeks.
***** Alternative regimen (1): [[drug name]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
*[[Folic Acid|Folic acid]] 1mg PO q24h or [[leucovorin]] weekly is usually added to [[MTX]] to avoid side effects.
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)
'''Therapy for resistant disease and flares'''
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h for 14–21 days  (maximum,500 mg per dose)
*The patients who started on [[DMARDs]] and [[NSAIDs]] initially for 10 to 14 days, add oral [[glucocorticoids]].
** 2.2 '<nowiki/>'''''Other Organ system involved 2''''''
*Preferred regimen: [[Glucocorticoids]] 5 to 20mg/day PO depending on the severity of the disease.<ref name="pmid16258899">{{cite journal |vauthors=Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF, van Krugten MV, Breedveld FC, Dijkmans BA |title=Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial |journal=Arthritis Rheum. |volume=52 |issue=11 |pages=3381–90 |date=November 2005 |pmid=16258899 |doi=10.1002/art.21405 |url=}}</ref><ref name="pmid18662933">{{cite journal |vauthors=van der Kooij SM, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Güler-Yüksel M, Zwinderman AH, Kerstens PJ, van der Lubbe PA, de Beus WM, Grillet BA, Ronday HK, Huizinga TW, Breedveld FC, Dijkmans BA, Allaart CF |title=Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis |journal=Ann. Rheum. Dis. |volume=68 |issue=6 |pages=914–21 |date=June 2009 |pmid=18662933 |doi=10.1136/ard.2008.092254 |url=}}</ref>
**: '''Note (1):'''  
*Intraarticular glucocorticoids are used in patient resistant to oral glucocorticoids.
**: '''Note (2)''':  
*Preferred regimen: Intraarticular glucocorticoids 40 mg once for a large joint,  30 mg once for medium-sized joints, and 10 mg  once for small joints.<ref name="pmid29129326">{{cite journal |vauthors=Xu C, Peng H, Li R, Chai W, Li X, Fu J, Liu K, Yu B, Jia C, Chen J |title=Risk factors and clinical characteristics of deep knee infection in patients with intra-articular injections: A matched retrospective cohort analysis |journal=Semin. Arthritis Rheum. |volume= |issue= |pages= |date=October 2017 |pmid=29129326 |doi=10.1016/j.semarthrit.2017.10.013 |url=}}</ref>
**: '''Note (3):'''
'''Flares'''
*** 2.2.1 '''Adult'''
*There is the severity of symptoms of ongoing treatment. We can add another DMARDs with methotrexate or replace with another DMARDs.
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 2 g IV q24h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 2 g IV q8h for 14 (14–21) days
***** Alternative regimen (2): [[drug name]] 18–24 MU/day IV q4h for 14 (14–21) days
**** Oral regimen
***** Preferred regimen (1): [[drug name]] 500 mg PO q8h for 14 (14–21) days
***** Preferred regimen (2): [[drug name]] 100 mg PO q12h for 14 (14–21) days
***** Preferred regimen (3): [[drug name]] 500 mg PO q12h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
***** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
***** Alternative regimen (3):[[drug name]] 500 mg PO q6h for 14–21 days
*** 2.2.2 '''Pediatric'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
***** Alternative regimen (1): [[drug name]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
***** Alternative regimen (2):  [[drug name]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day)
**** Oral regimen
***** Preferred regimen (1): [[drug name]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Preferred regimen (2): [[drug name]] 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
***** Preferred regimen (3): [[drug name]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Alternative regimen (1): [[drug name]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)


==References==
==References==

Latest revision as of 13:35, 31 March 2024

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

Overview

The mainstay of treatment of rheumatoid arthritis is pharmacotherapy. Early diagnosis of rheumatoid arthritis is helpful in treatment. Choice of treatment depends on various factors such as stage of disease, comorbid conditions, stage of therapy and presence of severe prognostic signs. There are two types of therapies- non-pharmacological therapy and pharmacological therapy. There are different drug regimen depending upon the stage of the disease. In active stage, combined therapy include disease-modifying antirheumatic drugs (DMARDs) are used along with the anti-inflammatory drugs. Therapy for resistant disease and flares is the addition of oral glucocorticoids. In case of the flare, add another DMARDs with methotrexate or replace with another DMARDs.

Medical Therapy

The mainstay of treatment of rheumatoid arthritis is pharmacotherapy. Early diagnosis of rheumatoid arthritis is helpful in treatment.

Choice of treatment depends on the following factors:

  • Stage of disease (eg, mild/moderate/severe).
  • Associated with other comorbid conditions.
  • Stage of therapy (eg, initial versus subsequent therapy in patients resistant to treatment).
  • Presence of severe prognostic signs.

Non-pharmacological treatment

Pharmacological treatment

Test to be done before starting the therapy

Various disease-modifying antirheumatic drugs (DMARDs) used are:

1)Leflunomide:

  • Preferred regimen: Loading dose is 100 mg PO q24h for 3 days, the maintenance dose is 20 mg q24h (Contraindications in pregnancy)

2)Sulfasalazine:

  • Preferred regimen: Initial dose: 500 mg PO q24h, the maintenance dose is 2 g PO once in 7days

3)Hydroxychloroquine:

  • Preferred regimen: Initial dose: 400 mg PO q24h x 3months, the maintenance dose is 300 mg PO q24h (Special instructions an eye examination is required before starting the therapy)

4)Rituximab:

  • Preferred regimen:1000 mg IV 2 doses given 2 weeks apart, in combination with MTX

5)Tocilizumab:

  • Preferred regimen: 4mg/kg once every 4 weeks

6)Azathioprine:

  • Preferred regimen: Initial dose 1mg/kg PO q24h for 6 to 8 weeks, the maintenance dose is reduction of dose 0.5mg/kg every week for 4 weeks

7) Cyclosporin:

  • Preferred regimen: 2.5mg/kg PO q12h for 8 weeks
  • It is used in patients who are unresponsive to methotrexate

8) Anakinra

  • Preferred regimen: 100 mg SC q24h
  • This is used for slowing the progression of moderately to severely active RA

9) Abatacept:

  • Preferred regimen: dose is according to body weight such as <60kg -500mg, 60 to 100kg- 750mg and more than 100kg is 1000mg IV followed by same dose at 2 weeks, 4 weeks, and every 4 weeks afterwards
  • This is used for moderately to severely active RA.

10) Baricitinib:

  • The recommended dose of baricitinib is 2 mg once daily
  • FDA approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies

DMARDs and TNF Inhibitors:

1)Infliximab:

  • This is the monoclonal antibody against TNF-α
  • Preferred regimen: 3 mg/kg IV at weeks 0, 2, and 6 and then every 4-8 weeks, usually with MTX

2)Etanercept:

  • This is a bivalent p75–TNF receptor attached to the Fc portion of IgG human antibody
  • Preferred regimen: 25 mg SC 2 times weekly or 50 mg SC once weekly, with or without concomitant MTX

3)Golimumab:

  • This is a human monoclonal antibody to TNF-α which inhibits TNF-α bioactivity
  • Preferred regimen: 50 mg SC once every month

4)Certolizumab:

  • This is a pegylated anti−TNF-α agent
  • Preferred regimen: First dose of 400 mg SC followed by 2 doses of 400 mg SC at 2nd and 4th week, followed by 200 mg every other week

5)Adalimumab:

  • This is the recombinant human IgG1 monoclonal antibody and it binds to TNF-α and blocks interaction with p55 and p75 cell-surface TNF receptors
  • Preferred regimen: 40mg SC every other week. No clear benefit of 80 mg every other week[1].

Different drug regimen depending upon the stage of disease:

Active disease:[2][3]

  • Combined therapy include disease-modifying antirheumatic drugs (DMARDs) are used along with the anti-inflammatory drugs.
  • The first line of the drug is methotrexate along with anti-inflammatory drugs like NSAIDs and glucocorticoids.
  • Preferred regimen : Methotrexate 7.5 mg PO weekly for 4 weeks.
  • Followed by an increase in dose by 2.5mg PO or 5mg PO depending on the severity of disease and renal function.
  • Monitoring of renal function is done after 4 weeks.
  • Folic acid 1mg PO q24h or leucovorin weekly is usually added to MTX to avoid side effects.

Therapy for resistant disease and flares

  • The patients who started on DMARDs and NSAIDs initially for 10 to 14 days, add oral glucocorticoids.
  • Preferred regimen: Glucocorticoids 5 to 20mg/day PO depending on the severity of the disease.[4][5]
  • Intraarticular glucocorticoids are used in patient resistant to oral glucocorticoids.
  • Preferred regimen: Intraarticular glucocorticoids 40 mg once for a large joint, 30 mg once for medium-sized joints, and 10 mg once for small joints.[6]

Flares

  • There is the severity of symptoms of ongoing treatment. We can add another DMARDs with methotrexate or replace with another DMARDs.

References

  1. ↑ Rau R (2002). "Adalimumab (a fully human anti-tumour necrosis factor alpha monoclonal antibody) in the treatment of active rheumatoid arthritis: the initial results of five trials". Ann Rheum Dis. 61 Suppl 2 (Suppl 2): ii70–3. doi:10.1136/ard.61.suppl_2.ii70. PMC 1766697. PMID 12379628.
  2. ↑ Emery P, Breedveld FC, Hall S, Durez P, Chang DJ, Robertson D, Singh A, Pedersen RD, Koenig AS, Freundlich B (August 2008). "Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial". Lancet. 372 (9636): 375–82. doi:10.1016/S0140-6736(08)61000-4. PMID 18635256.
  3. ↑ Darzi A, Harfouche M, Arayssi T, Alemadi S, Alnaqbi KA, Badsha H, Al Balushi F, Elzorkany B, Halabi H, Hamoudeh M, Hazer W, Masri B, Omair MA, Uthman I, Ziade N, Singh JA, Christiansen R, Tugwell P, Schünemann HJ, Akl EA (October 2017). "Correction to: Adaptation of the 2015 American College of Rheumatology treatment guideline for rheumatoid arthritis for the Eastern Mediterranean Region: an exemplar of the GRADE Adolopment". Health Qual Life Outcomes. 15 (1): 214. doi:10.1186/s12955-017-0791-9. PMC 5658904. PMID 29073913.
  4. ↑ Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF, van Krugten MV, Breedveld FC, Dijkmans BA (November 2005). "Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial". Arthritis Rheum. 52 (11): 3381–90. doi:10.1002/art.21405. PMID 16258899.
  5. ↑ van der Kooij SM, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Güler-Yüksel M, Zwinderman AH, Kerstens PJ, van der Lubbe PA, de Beus WM, Grillet BA, Ronday HK, Huizinga TW, Breedveld FC, Dijkmans BA, Allaart CF (June 2009). "Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis". Ann. Rheum. Dis. 68 (6): 914–21. doi:10.1136/ard.2008.092254. PMID 18662933.
  6. ↑ Xu C, Peng H, Li R, Chai W, Li X, Fu J, Liu K, Yu B, Jia C, Chen J (October 2017). "Risk factors and clinical characteristics of deep knee infection in patients with intra-articular injections: A matched retrospective cohort analysis". Semin. Arthritis Rheum. doi:10.1016/j.semarthrit.2017.10.013. PMID 29129326.

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