Alternatives to methotrexate for the initial treatment of rheumatoid arthritis in adults
- Stanley Cohen, MD
Stanley Cohen, MD
- Clinical Professor of Medicine
- University of Texas Southwestern Medical School
- Ted R Mikuls, MD, MSPH
Ted R Mikuls, MD, MSPH
- Umbach Professor of Rheumatology
- University of Nebraska Medical Center and Omaha VA Medical Center
The treatment of rheumatoid arthritis (RA) is directed toward the control of synovitis and the prevention of joint damage, which begins early in the course of disease and may ultimately result in disability. Patients are less likely to respond well to therapy the longer active disease persists, and it is widely accepted that patients with active RA should be treated with disease-modifying antirheumatic drugs (DMARDs) at the earliest stage of disease, ideally within less than three months of symptom onset. (See "General principles of management of rheumatoid arthritis in adults", section on 'Prognosis' and "General principles of management of rheumatoid arthritis in adults", section on 'Early use of DMARDs'.)
The most commonly used DMARD for the initial treatment of RA is methotrexate (MTX), although some patients are unable or reluctant to take this drug, and alternative agents are sometimes necessary as the initial DMARD in place of MTX. The choice of therapeutic agents, including both antiinflammatories and DMARDs, is influenced by multiple factors. (See 'Approach to management' below and "Initial treatment of rheumatoid arthritis in adults".)
The alternatives to MTX as the initial DMARD for the treatment of patients with active RA will be reviewed here. A more comprehensive description of the general principles of RA management and the initial treatment of RA, as well as the diagnosis and differential diagnosis of RA and the treatment of disease resistant to initial therapy, are presented separately. (See "General principles of management of rheumatoid arthritis in adults" and "Initial treatment of rheumatoid arthritis in adults" and "Diagnosis and differential diagnosis of rheumatoid arthritis" and "Treatment of rheumatoid arthritis in adults resistant to initial nonbiologic DMARD therapy" and "Treatment of rheumatoid arthritis in adults resistant to initial biologic DMARD therapy".)
APPROACH TO MANAGEMENT
Alternatives to methotrexate (MTX) are sometimes used for the initial treatment of rheumatoid arthritis (RA) because of either comorbidities that present an absolute or relative contraindication to MTX, the initial disease-modifying antirheumatic drug (DMARD) usually employed for treating RA, or because of patient or clinician preferences. (See "Initial treatment of rheumatoid arthritis in adults".)
The choice of the alternative agent to MTX is largely based upon evidence from indirect comparisons and limited head-to-head comparisons; and upon disease severity and prognostic features; comorbidities; patient preferences regarding relative risks and benefits and route of administration; and regulatory, insurance, and cost limitations. (See 'Choice of therapy' below.)
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- APPROACH TO MANAGEMENT
- GENERAL PRINCIPLES
- ASSESSMENT OF DISEASE ACTIVITY AND PROGNOSIS
- Disease activity
- Prognostic markers
- OTHER MANAGEMENT ISSUES
- PRINCIPLE TREATMENT CHOICES
- Choice of therapy
- Nonbiologic traditional DMARD alternatives to methotrexate
- - Leflunomide
- - Sulfasalazine
- Tumor necrosis factor inhibitors
- Other alternative agents
- - Tofacitinib
- - Tocilizumab
- - Other agents
- SPECIAL POPULATIONS
- Limited arthritis without adverse prognostic signs
- - General approach
- - Hydroxychloroquine
- Pregnancy, comorbidities, and other special considerations
- MONITORING AND REEVALUATION
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS