Musculoskeletal rheumatic complications of immune checkpoint inhibitor therapy: A single center experience

Semin Arthritis Rheum. 2019 Jun;48(6):1127-1132. doi: 10.1016/j.semarthrit.2018.10.012. Epub 2018 Oct 16.

Abstract

Background: The use of immune checkpoint inhibition (ICI) has revolutionized cancer treatment. However, these medications are associated with significant and potentially debilitating immune-related adverse events (irAEs). While certain toxicities have been well studied, rheumatic complications have been less widely recognized and characterized.

Methods: We report our experience of patients who were evaluated by rheumatology after the development of a suspected rheumatic irAE following ICI treatment. Cases of rheumatic irAEs were included if active rheumatic signs or symptoms developed during or after ICI treatment and were confirmed by a treating rheumatologist.

Results: Twenty-nine patients were evaluated by rheumatology for suspected rheumatic irAEs. Eighteen patients had confirmed toxicity including inflammatory arthritis (n = 12) and PMR (n = 6). Twelve patients had de novo toxicity and six had a flare of a pre-existing rheumatic condition. The onset of de novo toxicity occurred late into treatment (median 38 weeks), while patients with pre-existing rheumatic disease flared soon after initiation of ICI treatment (median 4.6 weeks). Management often required systemic or intra-articular steroids, with initiation of disease modifying anti-rheumatic drug (DMARD) therapy in those unable to wean off steroids.

Conclusion: De novo rheumatic irAEs are generally delayed in onset after ICI initiation, while flares of pre-existing rheumatic conditions occur shortly after ICI initiation. Effective management often requires systemic corticosteroids as well as DMARDs in a subset of patients. Future prospective studies are needed to accurately describe the incidence and spectrum of rheumatic irAEs and to identify the most effective management strategies.

Keywords: Immune checkpoint inhibition; Immunotherapy; Inflammatory arthritis; irAEs.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / adverse effects*
  • Arthritis, Psoriatic / chemically induced*
  • Arthritis, Rheumatoid / chemically induced*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Male
  • Melanoma / drug therapy
  • Middle Aged
  • Polymyalgia Rheumatica / chemically induced*
  • Prospective Studies
  • Skin Neoplasms / drug therapy

Substances

  • Antineoplastic Agents, Immunological