The Medical Letter ® on Drugs and Therapeutics Objective Drug Reviews Since 1959 Volume 56 ISSUE ISSUE No 1433 1458 December 22, 2014 IN THIS ISSUE Drugs for Rheumatoid Arthritis p 127 Volume 56 Important Copyright Message FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter, Inc publications are protected by U.S and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with U.S and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 The Medical Letter ® on Drugs and Therapeutics Objective Drug Reviews Since 1959 Volume 56 ISSUE ISSUE No December 22, 2014 Take CME exams IN THIS ISSUE 1433 1458 Drugs for Rheumatoid Arthritis Volume 56 Related article(s) since publication RECOMMENDATIONS For initial treatment of rheumatoid arthritis, most expert clinicians prescribe a disease-modifying antirheumatic drug (DMARD) and add a nonsteroidal anti-inflammatory drug (NSAID) or a corticosteroid to control symptoms Methotrexate is generally the DMARD of choice; hydroxychloroquine and sulfasalazine are safer alternatives that may be appropriate in the mildest cases In patients with moderate to severe disease, combining a biologic agent with a DMARD (usually methotrexate) for initial treatment may provide better disease control than a DMARD alone can be used to treat mild, moderate, or severe RA For mild disease, some clinicians prefer to start with hydroxychloroquine (Plaquenil, and generics) and/or sulfasalazine (Azulfidine, and others) METHOTREXATE — Methotrexate is usually the standard of care for initial DMARD therapy Even in low doses, it can decrease symptoms, limit joint damage, and improve long-term outcomes The antirheumatic effect of methotrexate is usually apparent within 4-6 weeks, but sometimes can take several months DMARDs Adverse Effects – In low doses, methotrexate is usually well tolerated, but it can cause stomatitis, anorexia, nausea, vomiting, abdominal cramps, aminotransferase elevations and, rarely, hepatic fibrosis Parenteral administration can decrease the GI adverse effects associated with oral administration of the drug Many rheumatologists would not prescribe methotrexate for patients with pre-existing liver disease or for those who consume large amounts of alcohol Hepatic transaminases should be monitored before and during treatment and patients at risk for hepatitis B and C should be screened before starting the drug Disease-modifying antirheumatic drugs (DMARDs) are used early in the treatment of rheumatoid arthritis (RA) to achieve clinical remission, prevent irreversible damage to joints, and minimize toxicity associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids.1 DMARDs generally not have an immediate analgesic effect, but over time can control symptoms and have been shown to delay and possibly stop progression of the disease Methotrexate (Rheumatrex, and others) is generally the first DMARD prescribed; it Methotrexate is an antifolate that is toxic to all rapidly dividing cells; complete blood counts should be monitored monthly Supplements containing folic acid (1-4 mg daily) or folinic acid (2.5-10 mg weekly, 24 hours after the methotrexate dose) are recommended to decrease adverse effects Bone marrow suppression can be treated with leucovorin rescue Infections such as herpes zoster may be more common in patients taking the drug Methotrexate use has rarely been associated with localized lymphoma, which often regresses when methotrexate is discontinued Tumor necrosis factor (TNF) inhibitors are typically the first-line biologic agents prescribed after an inadequate response to DMARD therapy, often in combination with methotrexate For patients who not respond adequately to one TNF inhibitor, switching to another TNF inhibitor or a non-TNF biologic agent may be effective 127 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter ® Vol 56 (1458) December 22, 2014 Table Some DMARDs for Rheumatoid Arthritis Drug Some Available Formulations Usual Adult Dosage1 Methotrexate, oral – generic Rheumatrex (Dava) Trexall (Duramed/Barr) 2.5 mg tabs Induction: 7.5-10 mg PO once/wk Maintenance: 7.5-25 mg PO once/wk3 $ 33.30 134.50 65.60 Methotrexate, injectable – generic Otrexup (Antares) 2, 4, 10 mL vials (25 mg/mL) 10, 15, 20, 25 mg in 0.4 mL auto-injectors 7.5 mg-30 mg auto-injectors7 Induction: 7.5 mg PO once/wk4,5 Maintenance: 10-25 mg IM or SC once/wk5,6 5.80 548.00 Hydroxychloroquine sulfate - generic Plaquenil (Covis) 200 mg tabs Induction: 400-600 mg/day PO x 4-12 wks Maintenance: 200-400 mg/day PO 57.20 128.20 Sulfasalazine – generic8 Azufidine (Pfizer)8 enteric-coated – generic Azulfidine EN-tabs 500 mg tabs Induction: 3-4 g/day in divided doses PO Maintenance: g/day in divided doses PO 22.30 98.90 27.90 129.10 Rasuvo (Medac) Leflunomide – generic Arava (Sanofi) Cost2 5, 7.5, 10, 15 mg tabs 448.00 500 mg tabs 10, 20 mg tabs 10, 20, 100 mg tabs Induction: 100 mg/day PO x days9 Maintenance: 10-20 mg/day PO 41.50 1066.50 Dosage adjustment may be needed for hepatic or renal impairment Approximate WAC for 30 days’ treatment with the lowest usual maintenance dosage WAC = wholesaler acquisition cost or manufacturer’s published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price Source: AnalySource® Monthly December 5, 2014 Reprinted with permission by First Databank, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy In patients who cannot tolerate the single dose, methotrexate can be given in divided doses The dosage can be increased over 1-2 months to 25 mg once/wk An oral formulation of methotrexate should be used for induction therapy with Otrexup and an oral or SC formulation of methotrexate can be used with Rasuvo Intramuscular (IM) or subcutaneous (SC) methotrexate once weekly (in the same dose as the oral formulation) may be helpful for patients who have adverse gastrointestinal effects from the oral formulation or lose benefit over time because of poor absorption Otrexup and Rasuvo are only for subcutaneous use Maintenance dosage for Rasuvo is 7.5-30 mg/wk Rasuvo is available in 7.5 mg/0.15 mL, 10 mg/0.2 mL, 12.5 mg/0.25 mL, 15 mg/0.3 mL, 17.5 mg/0.35 mL, 20 mg/0.4 mL, 22.5 mg/0.45 mL, 25 mg/0.5 mL, 27.5 mg/0.55 mL, and 30 mg/0.6 mL single-use auto-injectors Not FDA-approved for treatment of rheumatoid arthritis Some expert clinicians omit induction therapy because of GI intolerability Interstitial pneumonitis, which can be severe, occurs in