Psoriatic Arthritis: Drug Therapy

Therapy goals

  • Improvement of the symptomatology
  • Low disease activity, ideally remission (disappearance of disease symptoms).
  • Prevention of structural damage and normalization of function.

Therapy recommendations

Therapy is based on the treat-to-target concept, i.e., tight therapeutic timeline and orientation to strict goals.

  • For the relief of musculoskeletal symptoms:
    • Non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac or ibuprofen.
    • Glucocorticoid injections (weaker evidence and strength of recommendation than NSAIDs); systemic glucocorticoid therapy is indicated only when conventional measures have failed to improve disease activity, but carries the risk of worsening skin symptoms.
  • For active enthesitis (inflammation of the tendon insertions near the joints) and/or dactylitis (“finger inflammation”) that has not responded adequately to NSAIDs or glucocorticoid injections, TNF-alpha inhibitors or the new IL-12/23 or IL-27 inhibitors are recommended (see below).According to GRAPPA, the best evidence for enthesitis is for TNF-alpha and IL-12/23 inhibitors.

Therapy with a conventional DMARD should be considered early in patients with peripheral arthritis, particularly if there are numerous swollen joints, structural damage due to inflammation, and high C-reactive protein (CRP) and/or clinically relevant extra-articular manifestations. For predominant peripheral arthritis without prior DMARD therapy, the best evidence is for DMARDs (methotrexate, leflunomide, sulfasalazine) and tumor necrosis factor alpha (TNF alpha) inhibitors. Disease-modifying therapy: DMARDs (disease modifying antirheumatic drugs).

  • Conventional synthetic DMARDs (csDMARDs) – first-line therapy.
    • Immunosuppressants
      • Methotrexate (MTX) – first-line agent (esp. with relevant skin involvement).
      • Alternatively: leflunomide
      • Caveat: If steroids are administered without concomitant immunosuppression, arthritis improves but there is a risk of dramatic worsening of psoriasis!
    • Sulfonamides (sulfasalazine).
      • For mild joint infestation
      • 40% skin improvement
    • Notes:
      • In patients with active dactylitis (finger/toe inflammation) and/or enthesitis (inflammation of tendon/vision attachments), biologics (bDMARDs) may be given as first-line agents instead of csDMARDs (TNF-α inhibitors or IL-12/IL-23 antagonist or IL-17 antagonist).
      • Patients with axial symptoms (inflammatory symptoms of the spine or sacroiliac joint (ISG; sacroiliac joint)): TNF-α inhibitors (anti-TNF): first-line agent.
  • If the patient does not respond to a csDMARD as desired: use of biologics (biologicals; bDMARDs); reserve drug for treatment resistance (second-line therapy).
    • preferred use: TNF-α inhibitors (anti-TNF).
      • Z. E.g., etanercept, infliximab, adalimumab
      • High response rates in terms of effectiveness on psoriasis, joints, enthesitis, dactylitis, axial symptoms and structural damage to the joints; side effects and contraindications note!
    • If no sufficient effect occurs under therapy of at least one conventional DMARD and contraindication (contraindications) for TNF-α inhibitor, the use of one of the new biologics targeting interleukin-12/23 or IL-17 may be considered, if necessary in combination with methotrexate:
      • Interleukin-12/interleukin-23 antagonist (IL-12/IL-23 antagonist): ustekinumab.
      • Interleukin-17 antagonist (IL-17 antagonist): secukinumab
      • Both antagonists are effective in relation to joints, dactylitis and enthesitis.
  • When patients with inadequate response to at least one conventional DMARD cannot be treated with a biologic because of contraindications or high risk of infection:
    • PDE-4 inhibitor (“target synthetic DMARDs”; tsDMARDs): apremilast.

Further notes

  • Red-hand letter on apremilast (oral PDE-4 inhibitors – “target synthetic DMARDs (tsDMARDs)”): new evidence on suicidal ideation and behavior.
  • A study of 996 patients showed that radiographic progression was halted in 80 to 88 percent of all PsA patients treated with secukinumab, with 300 mg being the most effective dose.