- Indian Rheumatology association
Immune checkpoint inhibitors (ICIs) have dramatically changed the treatment paradigms of cancer in the past decade. These agents have shown to provide significant survival benefits, after traditional chemotherapies have failed.
Two main interactions that control T-cell activation are cytotoxic lymphocyte antigen protein 4 (CTLA-4, also called CD152) on T cells binding with CD80/86 (also called B7-1 and B7-2) on antigen-presenting cells, and programmed cell death receptor 1 (PD-1) binding to programmed cell death ligand 1 (PD-L1, also known as B7-H1) or programmed cell death ligand 2 (PD-L2 [B7-H2]). By blocking these inhibitory pathways, checkpoint inhibitors allow for increased activation of T cells and a greater immune response against tumors. The first approved IСΙ, ipilimumab, blocks the binding of CTLA-4 to its ligands CD80/86. Subsequent ІСIs have targeted PD-1 (pembrolizumab, nivolumab, cemiplimab) or PD-L1 (eg, atezolizumab, avelumab, durvalumab).
Common rheumatic irAEs are arthritis, myositis, polymyalgia rheumatica, vasculitis, Sjögren’s-syndrome-like sicca symptoms, psoriasis-like rash, systemic-sclerosis-like skin sclerosis, and lupus-like nephritis. The occurrence of rheumatic irAEs could be a marker for an efficient and durable antitumor response.
Inflammatory arthritis has been the most commonly reported rheumatologic irAE. The arthritis can develop at almost any time during ICI therapy, from two weeks to over a year from ΙСI initiation.
Patients treated with PD-1 or PD-L1 monotherapy are more likely to have small joint inflammatory arthritis.
Joint radiographs are recommended as a part of the routine assessment, primarily due to the early onset of erosions. Ultrasound and MRI of selected joints may also be valuable.
Type of arthritis | Treatment | ICI therapy Continuation/discontinuation |
Mild forms of arthritis | NSAIDs/ low dose steroids | ІСΙ therapy continued |
Moderate or severe arthritis | Moderate to high dose oral steroids | In patients who require higher doses of steroids, ICI is sometimes held temporarily. Restarted when GCs are tapered off to low dose |
Persistent Inflammatory arthritis where steroids cannot be weaned off | csDMARDs Sulphasalazine, Hydroxychloroquine or Methotrexate | Case- case to basis |
Refractory Inflammatory arthritis | Anti TNF therapy IL 6 Inhibitors | Case- case to basis |
Approximately one-third or more of patients with pre-existing rheumatic disease have experienced flares of their prior disorder in association with treatment using ІCΙѕ for malignancy. Many were managed with steroids or other treatments, but some have required discontinuation, usually temporarily, of their ІСI. Generally, the mutual administration of ICIs and anti rheumatic drugs, such as hydroxychloroquine and sulfasalazine, is safe and does not diminish the efficacy of immunotherapy. Even if the risk of disease progression is higher in these patients, there is no reason to exclude them from receiving ICI treatment, especially considering rheumatic disease itself is not life-threatening.
