Background/Purpose:

Rheumatic immune related adverse events (irAEs) from checkpoint inhibitor (ICI) therapy remain poorly understood. In our early experience with rheumatic irAEs we encountered patients presenting with polymyalgia rheumatica (PMR)-like clinical phenotypes. This entity has also been described in the literature. It is the purpose of this study to describe the cases of PMR-like syndrome secondary to ICI reported in the literature to date, and determine if they meet the 2012 EULAR/ACR criteria for PMR¹.

Methods:

A systematic literature search was performed in PubMed and Ovid Embase using the search terms: “polymyalgia rheumatica”[MESH] OR “polymyalgia rheumatic” AND “ immunotherapy” OR
checkpoint inhibitor therapy”. We determined how many cases provided enough data to apply the EULAR/ACR criteria for PMR (age > 50, elevated ESR or CRP, and bilateral shoulder aching) and these cases were designated “A level” evidence. The remaining cases, with incomplete or insufficient data, were designated “B level” evidence.

Results:

A total of 39 patients were included for analysis, including 6 cases from our center. Among these, 25 (64%) were designated A level. The remaining 14 (36%) were designated B level and thus censored from further evaluation. Within group A, 20 cases fulfilled complete EULAR/ACR criteria for a diagnosis of PMR. Three patients also met imaging criteria. The main reason why patients did not meet criteria was because they had other joint involvement – most commonly knees, followed by elbows and hands. Two patients had low-positive rheumatoid factor.  One case described a patient with RS3PE. In the whole group, the specific checkpoint inhibitor was reported in 24 cases. 7 were exposed to nivolumab, 4 to combination ipilimumab/nivolumab, 5 to pembrolizumab, 3 to ipilimumab and 5 to PD-1 or PD-L1 agents. Of note, 3 cases of giant cell arteritis have been described with ICI therapy: 2 in the setting of PMR and one isolated case.

Table. Cases from our irAE clinic

Conclusion:

In this combined analysis 36% of reported cases of PMR were based on incomplete reporting data making verification problematic. Of those with enough data for evaluation nearly 80% met current classification criteria for PMR. Among those with insufficient evidence atypical features (synovitis, positive serology) were present that may indicate an alternative inflammatory rheumatic manifestation of unclear nosology. Prospective registry-based studies with adequate assessment of data are urgently needed.

References

1.       Dasgupta B, et al. 2012 provisional classification criteria for polymyalgia rheumatic: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis 2012;71:484-492.