Remitting seronegative symmetrical synovitis with pitting edema and polymyalgia-like syndromes following cancer immunotherapy with checkpoint inhibitors: causal link, potential association or else?

Dear Editors, I read with interest the manuscript entitled “Rheumatic related adverse events from checkpoint inhibitor therapy: a case series”, recently published in Beyond Rheumatology, where Laria et al. reported three patients with rheumatologic immuno-related adverse events (r-IRAEs) following cancer immunotherapy with checkpoints inhibitors (ICIs). Their case-series gives food for thought. No doubt. In particular, their case 3 described a 58-year-old man with metastatic melanoma who reported remitting seronegative symmetrical synovitis with pitting edema (RS3PE) associated with polymyalgia rheumatica-like (PMR-like) manifestations following 11 treatment cycles with pembrolizumab. (1) I wish to share two considerations, that could be useful to readers in their clinical practice. The first consideration revolves around the definition of rheumatic manifestations following ICI therapy as an adverse drug reaction (ADR). A commonly used algorithm is the ADR Probability Scale developed in 1981 by Naranjo and colleagues to standardize causality assessments. This scale estimates the probability that an adverse event is related to drug therapy. A list of 10 weighted questions examines factors such as temporal association with the drug administration and event occurrence; alternative causes if any; drug levels; and previous patient experience with the same drug. The sum of the scores ranges from –4 to +13: a score >9 indicates that the drug definitely caused the ADR; a score between 5 and 8 indicates that the drug probably caused the ADR; a score between 1 and 4 indicates that the ADR was possibly caused by the drug; and a score