Treatment of Rheumatoid Arthritis with MTX Contraindication When a Biologic or JAK Inhibitor Has Not Achieved Targets

This protocol applies to patients with rheumatoid arthritis who have a contraindication or early intolerance to methotrexate, have no poor prognostic factors, and whose initial biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD) therapy did not reach the expected treatment goals.

Previous Treatment — Targets Not Achieved

A first bDMARD — adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, abatacept, rituximab, tocilizumab, or sarilumab — or a JAK inhibitor (tofacitinib, baricitinib, filgotinib, or upadacitinib) was used in this MTX-intolerant population but failed to achieve at least 50% improvement in disease activity within 3 months or sustained remission or low disease activity by 6 months.

Clinical Scenario

The patient has a contraindication to methotrexate or experienced early intolerance, and shows none of the following poor prognostic factors: no high-level RF or ACPA positivity, no persistently moderate or high disease activity despite csDMARD therapy, no high swollen joint count, no elevated acute phase reactant levels, no early erosions, and no failure of two or more csDMARDs.

Treatment Approach (Partial Overview)

The strategy at this stage centres on switching to another biologic or targeted synthetic DMARD — with consideration of an agent carrying a different mode of action from the one that previously failed. The complete selection algorithm, sequencing, and relevant clinical considerations are in the full structured protocol.

Treatment Targets

At least 50% improvement in disease activity within 3 months; sustained remission or low disease activity by 6 months.

Instant Access to Structured Evidence-Based Regimens

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.
If a bDMARD or tsDMARD has failed, treatment with another bDMARD or a tsDMARD should be considered; if one TNF or IL-6 receptor inhibitor therapy has failed, patients may receive an agent with another mode of action or a second TNF- or IL-6 receptor inhibitor.
bDMARDs and tsDMARDs should be combined with a csDMARD; in patients who cannot use csDMARDs as comedication, IL-6 pathway inhibitors and tsDMARDs may have some advantages compared with other bDMARDs.
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.

View source ↗