Mycophenolate Mofetil in Rheumatoid Arthritis
Mycophenolate mofetil (MMF) is NOT recommended for the treatment of rheumatoid arthritis and should not be used in this indication. Large, well-designed randomized controlled trials have definitively demonstrated that MMF lacks efficacy compared to placebo in patients with refractory RA 1.
Evidence Against MMF Use in RA
The most definitive evidence comes from three 24-week, randomized, double-blind trials involving 1,262 patients with advanced refractory RA 1. These patients had:
- Mean disease duration of 9.8-13 years
- Failed a median of 3-4 prior DMARDs
- American Rheumatism Association functional class II or III disease 1
In two placebo-controlled trials, MMF (1g twice daily) showed no significant difference from placebo in ACR20 response rates (19.7% vs 13.0% and 15.8% vs 10.1%; p > 0.05 for both studies) 1. The third active-comparator trial against cyclosporine was stopped prematurely due to lack of efficacy, and efficacy analyses were not even performed 1.
Current Guideline-Recommended Alternatives
First-Line Strategy After MTX Failure
When MTX fails or is not tolerated, EULAR guidelines provide clear alternatives 2, 3:
- If MTX contraindicated or intolerant: Switch to leflunomide or sulfasalazine as first-line alternatives 2, 3
- If no poor prognostic factors present: Change to another conventional synthetic DMARD (csDMARD) strategy 2
- If poor prognostic factors present (high RF/anti-CCP, very high disease activity, early joint damage): Add a biologic DMARD 2
Biologic DMARD Options
For patients with inadequate response to MTX and/or other csDMARDs, the following biologics combined with MTX are recommended 2:
- TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab)
- Abatacept
- Tocilizumab
- Rituximab (under certain circumstances) 2
Treatment Algorithm
Monitor disease activity every 1-3 months 2:
- If no improvement by 3 months: adjust therapy
- If target not reached by 6 months: change treatment strategy 2
Add low-dose glucocorticoids (≤10 mg/day prednisone equivalent) as bridging therapy for up to 6 months, then taper rapidly 2, 4.
Why MMF Failed in RA
While MMF showed some promise in early open-label studies from 1993 5, the subsequent large-scale controlled trials definitively refuted its efficacy 1. The drug's mechanism—inhibiting the de novo pathway of purine biosynthesis—proved insufficient to control RA disease activity despite its success in transplant rejection 5, 1.
Critical Pitfall to Avoid
Do not use MMF for RA treatment. It is not FDA-approved for this indication, lacks efficacy data, and delays appropriate therapy with proven DMARDs 1. The only potential exception would be in the rare context of systemic inflammatory or vital organ-threatening disease (such as lupus nephritis or vasculitis), where immunosuppressants including MMF may be initiated 2—but this is not standard RA treatment.
Appropriate Immunosuppressant Alternatives
If an immunosuppressant is specifically needed (e.g., for vital organ-threatening disease or contraindications to standard DMARDs), consider 2:
- Tacrolimus
- Cyclosporine A
- Azathioprine
These agents have established roles in specific clinical contexts, unlike MMF in RA 2.