Systemic lupus erythematosus medical therapy: Difference between revisions
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The mainstay of therapy for systemic lupus erythematosus (SLE) is to control disease activity and prevent organ damage. [[Pharmacology|Pharmacologic]] medical therapies for SLE include [[hydroxychloroquine]], [[Non-steroidal anti-inflammatory drug|NSAIDs]] like [[celecoxib]], and [[glucocorticoids]] like [[prednisone]]. [[Hydroxychloroquine]] is the drug of choice to treat SLE. All organ related complications of SLE should be treated seperately. | The mainstay of therapy for systemic lupus erythematosus (SLE) is to control disease activity and prevent organ damage. [[Pharmacology|Pharmacologic]] medical therapies for SLE include [[hydroxychloroquine]], [[Non-steroidal anti-inflammatory drug|NSAIDs]] like [[celecoxib]], and [[glucocorticoids]] like [[prednisone]]. [[Hydroxychloroquine]] is the drug of choice to treat SLE. All organ related complications of SLE should be treated seperately. | ||
==Medical Therapy== | ==Medical Therapy== | ||
Treatmen goals in systemic lupus erythematosus (SLE): | |||
* Ensure long-term survival | |||
* Achieve the lowest possible disease activity | |||
* Prevent organ damage | |||
* Minimize drug toxicity | |||
* Improve quality of life | |||
===== Pharmacological therapy for constitutional SLE ===== | ===== Pharmacological therapy for constitutional SLE ===== | ||
* Preferred regimen 1: Hydroxychloroquine (oral): 200 to 400 mg daily as a single daily dose or in 2 divided doses | * Preferred regimen 1: Hydroxychloroquine (oral): 200 to 400 mg daily as a single daily dose or in 2 divided doses | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]
Overview
The mainstay of therapy for systemic lupus erythematosus (SLE) is to control disease activity and prevent organ damage. Pharmacologic medical therapies for SLE include hydroxychloroquine, NSAIDs like celecoxib, and glucocorticoids like prednisone. Hydroxychloroquine is the drug of choice to treat SLE. All organ related complications of SLE should be treated seperately.
Medical Therapy
Treatmen goals in systemic lupus erythematosus (SLE):
- Ensure long-term survival
- Achieve the lowest possible disease activity
- Prevent organ damage
- Minimize drug toxicity
- Improve quality of life
Pharmacological therapy for constitutional SLE
- Preferred regimen 1: Hydroxychloroquine (oral): 200 to 400 mg daily as a single daily dose or in 2 divided doses
- Preferred regimen 2: Celecoxib for fever management even in SLE patients, even in those with “sulfa” allergy. Dosing: 100 to 200 mg twice daily
- Preferred regimen 3: Prednisone high doses of 40 to 60 mg/d for patients with severe SLE, and doses of 10 mg/d or less for milder SLE and treatment of cutaneous and musculoskeletal symptoms not responding to other therapies
- Alternative regimen 1: Mycophenolate for induction 1 g twice daily for 6 months in combination with a glucocorticoid or 2-3 g daily for 6 months in combination with glucocorticoids and for maintenance 0.5-3 g daily or 1 g twice daily or 1-2 g daily
- Alternative regimen 2: Cyclophosphamide (more for lupus nephritis) IV: 500 mg once every 2 weeks for 6 doses or 500 to 1,000 mg/m2 once every month for 6 doses or 500 to 1,000 mg/m2 every month for 6 months, then every 3 months for a total of at least 2.5 years
- Alternative regimen 3: Rituximab IV: 375 mg/m2 once weekly for 4 doses or 1,000 mg (flat dose) on days 0 and 15 or 500 to 1,000 mg on days 1 and 15
- Alternative regimen 4: Methotrexate Oral: Initial therapy with 7.5 mg once weekly; may increase by 2.5 mg increments weekly
- Alternative regimen 5: Azathioprine Oral: Initial 2 mg/kg/day; may reduce to 1.5 mg/kg/day after 1 month. It is usually used for nephritis treatment
Cutaneous lupus erythematosus
- Preferred regimen 1: twice daily application of a super high potency or high potency topical corticosteroid as the first-line therapies for patients with DLE or SCLE
- Hydrocortisone 1% or 2.5% for minimal disease activity on the face
- Triamcinolone acetonide 0.1% cream or fluocinonide 0.05% cream: trunk, extremity, or scalp disease
- Clobetasol propionate first-line therapy for acute flares of DLE
- Discontinue treatment in the absence of disease activity
- Alternative regimen 1: topical calcineurin inhibitor such as tacrolimus 0.1% ointment or pimecrolimus 1% cream
- Preferred regimen 2: intralesional corticosteroid injections for DLE or SCLE if an acute flare of DLE or SCLE doesn't respond to topical corticosteroid therapy for two to four week
- Alternative regimen 2: fail of local therapy or extensive disease manifestation are the indications of systemic medications like hydroxychloroquine 200 to 400 mg/day for at least six weeks, after improvement it should be decreased to 200 mg/day for maintenance therapy
- Alternative regimen 3: If antimalarial drugs are unsuccessful, add quinacrine 100 mg/day
Lupus nephritis treatment
- Aggressive antihypertensive therapy
- In patients with proteinuria, antiproteinuric therapy with blockade of the renin-angiotensin system include ACEIs and ARBs
- Lipid lowering with statin therapy
- Diffuse or focal proliferative LN:
- Preferred regimen: Immunosuppressive therapy with glucocorticoids plus either intravenous or oral mycophenolate mofetil: 0.5 g of mycophenolate mofetil twice daily for the first week, then 1 g twice daily for the second week, and thereafter increase the dose to 1.5 g twice daily
- Alternative regimen: IV cyclophosphamide instead of mycophenolate mofetil 500 mg every two weeks for a total of six doses
- Severe active disease:
- Preferred regimen: Glucocorticoid therapy is initiated with intravenous pulse methylprednisolone (250 mg to 1000 mg given over 30 minutes daily for three days) to induce a rapid immunosuppressive effect, followed by conventional doses
- Alternative regimen: Conventional doses of oral glucocorticoids (eg, 0.5 to 1 mg/kg per day of prednisone) without a pulse. Oral prednisolone at a dose of 60 mg/day, tapered every two weeks by 10 mg/day until 40 mg/day is reached, then tapered by 5 mg/day until 10 mg/day is reached
Raynaud phenomenon treatment
- Preferred regimen 1: Channel blocker (CCB) alone
- Preferred regimen 2: Antiplatelet therapy with low-dose aspirin (75 or 81 mg/day) in all patients with secondary RP
- Alternative regimen 1: Phosphodiesterase (PDE) inhibitor (eg, sildenafil) if there was no answer to CCBs. Sildenafil is begun at 20 mg once or twice daily
- Alternative regimen 2: Addition of topical nitroglycerin (NTG) in patients with an inadequate response to a CCB and for whom a PDE inhibitor is not available, effective, or well-tolerated
- Alternative regimen 3: Intravenous (IV) infusions of a prostaglandin (PG) for extremely severe patients
Treatment regimen based on the SLE manifestations
- Mild lupus manifestations:
- Hydroxychloroquine with and without nonsteroidal antiinflammatory drugs (NSAIDs), and/or short-term use of low-dose glucocorticoids (eg, ≤ 7.5 mg prednisone equivalent per day)
- Moderate lupus manifestations:
- Defined as having significant but non-organ-threatening disease
- Hydroxychloroquine plus short-term therapy with 5 to 15 mg of prednisone (or equivalent) daily. Prednisone is usually tapered once hydroxychloroquine has taken effect.
- A steroid-sparing immunosuppressive agent like azathioprine or methotrexate is often required to control symptoms.
- Severe or life-threatening manifestations:
- Secondary to major organ involvement
- An initial period of intensive immunosuppressive therapy (induction therapy) to control the disease and halt tissue injury.
- A short period of time treatment of high doses of systemic glucocorticoids (eg, intravenous “pulses” of methylprednisolone, 0.5 to 1 g/day for three days in acutely ill patients, or 1 to 2 mg/kg/day in more stable patients) alone or in combination with other immunosuppressive agents.
Fever management
- Preferred regimen: NSAIDs especially celecoxib with a dosing: 100 to 200 mg twice daily
- Alternative regimen 1: Acetaminophen 1000 mg every 6 hours; maximum daily dose: 3000 mg daily AND/OR
- Alternative regimen 2: Low to moderate doses of glucocorticoids
Chronic pain management
- Moderate pain should be treated with mild prescription opiates such as:
- Preferred regimen: Dextropropoxyphene
- Alternative regimen: Co-codamol (Acetaminophene+opioid): Acetaminophen (300 to 1,000 mg/dose)/codeine (15 to 60 mg/dose) every 4 hours as needed; adjust dose according to severity of pain and response of patient (maximum: acetaminophen 4,000 mg/codeine 360 mg per 24 hours)
- Moderate to severe chronic pain should be treated with stronger opioids such as:
- Preferred regimen 1: Hydrocodone: Single doses >40 mg or >60 mg with a total daily dose ≥80 mg
- Preferred regimen 2: Oxycodone: 5 to 15 mg every 4 to 6 hours as needed
- Alternative regimen 1:MS Contin: Opioid naive patients can have 5 to 10 mg every 4 hours as needed; usual dosage range between 5 to 15 mg every 4 hours as needed. Patients with prior opioid exposure may require higher initial doses.
- Alternative regimen 2: Methadone: Maximum initial dose 30 mg
- Alternative regimen 3: Fentanyl Duragesic Transdermal patch: A convenient treatment option for lupus chronic pain. It has a long lasting effect as well
Considerations
- Treatment recommendations are mostly based on the following:[6]
- Ensuring long-term survival
- Preventing organ damage
- Controlling disease activity
- Minimizing comorbidities
- Minimizing drug toxicity
- Treatment targets:
- Remission and prevention of flares
- Appropriate adjunct therapy:
- Vitamin D and calcium supplements for preventing osteoporosis in patients using corticosteroids
- Antihypertensive drugs and statins were also recommended in patients using corticosteroids
- Patients with more severe manifestations of the disease whom are not responsive to first line therapy like antimalarials or glucocorticoids should be considered for treatment with immunosuppressive agents like cyclophosphamide, azathioprine, mycophenolate mofetil, and methotrexate.
Adverse effects:
- Cutaneous atrophy is a potential side effect of the long-term use of topical corticosteroids
References
- ↑ DOEGLAS HM (1964). "CHRONIC DISCOID LUPUS ERYTHEMATOSUS TREATED WITH TRIAMCINOLONE AND PLASTIC OCCLUSION". Dermatologica. 128: 384–6. PMID 14162995.
- ↑ Rothfield N, Sontheimer RD, Bernstein M (2006). "Lupus erythematosus: systemic and cutaneous manifestations". Clin. Dermatol. 24 (5): 348–62. doi:10.1016/j.clindermatol.2006.07.014. PMID 16966017.
- ↑ Sárdy M, Ruzicka T, Kuhn A (2009). "Topical calcineurin inhibitors in cutaneous lupus erythematosus". Arch. Dermatol. Res. 301 (1): 93–8. doi:10.1007/s00403-008-0894-6. PMID 18797893.
- ↑ BJORNBERG A, HELLGREN L (1963). "Treatment of chronic discoid lupus erythematosus with fluocinolone acetonide ointment". Br. J. Dermatol. 75: 156–60. PMID 13971327.
- ↑ Ritschel WA, Hammer GV, Thompson GA (1978). "Pharmacokinetics of antimalarials and proposals for dosage regimens". Int J Clin Pharmacol Biopharm. 16 (9): 395–401. PMID 359493.
- ↑ Tunnicliffe DJ, Singh-Grewal D, Kim S, Craig JC, Tong A (2015). "Diagnosis, Monitoring, and Treatment of Systemic Lupus Erythematosus: A Systematic Review of Clinical Practice Guidelines". Arthritis Care Res (Hoboken). 67 (10): 1440–52. doi:10.1002/acr.22591. PMID 25778500.