What to Do When Leflunomide or Sulfasalazine Fails in Rheumatoid Arthritis with Methotrexate Contraindication and No Poor Prognostic Factors
This protocol covers patients with rheumatoid arthritis who cannot receive methotrexate (due to contraindication or early intolerance), have no poor prognostic features, and have not reached the treatment target on their initial conventional synthetic DMARD strategy.
Methotrexate is contraindicated or was not tolerated early. Poor prognostic factors are absent: no high-level RF or ACPA positivity, no persistently moderate-to-high disease activity despite prior csDMARD therapy, no high swollen joint count, no elevated acute-phase reactant levels, no early erosions, and no history of two or more csDMARD failures.
The initial csDMARD strategy — leflunomide or sulfasalazine with short-term bridging glucocorticoids — did not achieve at least 50% improvement in disease activity within 3 months, or sustained remission or low disease activity by 6 months. This protocol defines the next step.
The next step involves changing to or adding another conventional synthetic DMARD, in combination with a short-term glucocorticoid course. Specific agent selection and the full structured regimen are available in the complete protocol.
Treatment goals: at least 50% improvement in disease activity within 3 months; sustained remission or low disease activity by 6 months.
References
DOI: 10.1136/ard-2022-223356
- In patients with a contraindication to MTX (or early intolerance), leflunomide or sulfasalazine should be considered as part of the (first) treatment strategy.
- If the treatment target is not achieved with the first csDMARD strategy, in the absence of poor prognostic factors, other csDMARDs should be considered.
- Short-term glucocorticoids should be considered when initiating or changing csDMARDs, in different dose regimens and routes of administration, but should be tapered and discontinued as rapidly as clinically feasible.
- sulfasalazine has been previously recommended at a dose of 3000 mg per day and leflunomide at a dose of 20 mg per day without loading dose.
- Treatment should be aimed at reaching a target of sustained remission or low disease activity in every patient.
- Monitoring should be frequent in active disease (every 1-3 months); if there is no improvement by at most 3 months after the start of treatment or the target has not been reached by 6 months, therapy should be adjusted.