Treatment with Targeted Therapy in Patients with Psoriatic Arthritis and Inadequate Response to Methotrexate: Proposal for a Rational Strategy.

Introduction: The therapeutic arsenal for psoriatic arthritis (PsA) is gradually being expanded, but the use of these targeted treatments must be optimal. Our objective was to guide the choice of targeted therapy to use as first-line treatment in a patient with PsA in whom methotrexate (MTX) has failed.

Methods: We searched for literature data in PubMed with the appropriate keywords for the six points of our argument: (1) the tolerance of MTX; (2) the efficacy of targeted therapies combined with MTX vs monotherapy; (3) immunogenicity of anti-tumor necrosis alpha (TNFα) monoclonal antibodies (mAbs); (4) immunogenicity of anti-interleukin (IL)-17, anti-IL-12/23, and anti-IL-23 mAbs; (5) the therapeutic maintenance of anti-TNFα mAbs when combined or not with MTX; (6) the therapeutic maintenance of anti-IL-17 vs anti-TNFα mAbs as first-line targeted therapy.

Results: The proposed rational strategy is as follows: in case of initiation of an anti-TNFα agent, maintaining treatment with MTX seems preferable, even in the absence of evidence of the superior efficacy of the combination, to avoid immunization and reduced therapeutic maintenance; in case of initiation of anti-IL-17, anti-IL-12/23, anti-IL-23 agents, or Janus kinase (JAK) inhibitors, again in the absence of evidence of the superior efficacy of the combination, discontinuing MTX therapy may be possible, at least in two steps, after verifying the efficacy of the targeted therapy initiated on the joints and skin.

Conclusion: We have data from the literature to guide the choice of targeted therapy to use as first-line treatment in a patient with PsA in whom MTX has failed.