Pos1429 Immune Checkpoint Inhibitor-Mediated Polymyalgia Rheumatica Versus Primary Polymyalgia Rheumatica: Comparison of Disease Characteristics and Treatment Requirement

Background: The introduction of immune checkpoint inhibitors (ICI) has been a significant breakthrough in the field of oncology. However, removal of the brake on the immune system by ICI therapy can lead to serious auto-immune related adverse events (irAEs). One of the most common rheumatic irAEs is a polymyalgia rheumatica (PMR)-like syndrome, termed ICI-PMR 1. To date, it remains to be elucidated whether ICI-PMR is a true form of primary PMR or a separate disease entity. Moreover, the optimal management of ICI-PMR is unclear, despite concerns that immunosuppressive therapy may negatively impact the anti-tumour effects of ICI therapy. Objectives: To compare clinical characteristics, imaging findings and treatment requirements of patients with ICI-PMR and primary PMR. Methods: This single centre, retrospective cohort study compared patients with PMR secondary to ICI therapy for cancer (ICI-PMR; n=15) to patients with primary PMR (n=37). ICI-PMR was defined as a PMR-like syndrome occurring in patients who received at least one cycle of ICI, and who demonstrated predominant pain and stiffness in the shoulder and hip girdle, with ultrasonography and/or 18F-FDG-PET/CT demonstrating inflammation in at least two sites (i.e. two shoulders, two hips, or one shoulder and one hip). A comparison was made between clinical symptoms, laboratory markers, ultrasonography, 18F-FDG-PET/CT findings and treatment requirements related to PMR. Results: Patients with ICI-PMR less frequently fulfilled the EULAR/ACR classification criteria for PMR (n=10; 67%) than patients with primary PMR (n=36; 97%). Morning stiffness, weight loss and elevation of the ESR were less frequently seen in patients with ICI-PMR. No differences were observed regarding the presence of inflammatory lesions on ultrasound of the shoulders and hips between the two groups. However, the metabolic activity at these inflamed sites, as determined by18F-FDG-PET/CT, was significantly lower in the ICI-PMR group. The ICI-PMR group could be managed with lower initial glucocorticoid doses than typically needed in primary PMR. Eleven patients with ICI-PMR (73%) could be successfully managed with a prednisolone equivalent of ≤10mg daily, or no oral glucocorticoids at all. Oral glucocorticoid therapy could be tapered more quickly in the ICI-PMR group than in the primary PMR group (Figure 1), irrespective of ICI therapy continuation after ICI-PMR diagnosis. ICI therapy was continued without interruption at time of ICI-PMR diagnosis in eight patients (53%). In three (20%) patients, ICI therapy was eventually stopped at least partly due to ICI-PMR. ICI therapy led to good anti-tumour responses in most patients, with cancer progression observed only in three (23%) out of 13 patients with tumour response data available. Conclusion: Our findings support the notion that ICI-PMR is a different disease entity than primary PMR, and should be considered as a PMR-like syndrome. Although ICI-PMR and primary PMR share a cluster of symptoms related to inflammation in the shoulder and hip girdle, ICI-PMR is associated with less intense inflammation and a markedly lower treatment requirement than primary PMR. Although subsequent studies are necessary, our findings provide a framework for the diagnostic and therapeutic approach to this PMR-like-syndrome. REFERENCES: 1 Kostine M, Rouxel L, Barnetche T, et al. Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer - Clinical aspects and relationship with tumour response: A single-centre prospective cohort study. Ann Rheum Dis. 2018;77:393–8. Acknowledgements: NIL. Disclosure of Interests: Kornelis van der Geest speaker fee from Roche, research support from AbbVie, Olof Vermeulen: None declared, Elisabeth Brouwer speaker fee for a talk on GCA at a post EULAR symposium in the Netherlands, Riemer H.J.A. Slart unrestricted research grants by Pfizer and Siemens Healthineers, Maria Sandovici: None declared, Abraham Rutgers advisory board GSK, Chemocentryx, T. Jeroen Hiltermann advisory boards for Pfizer and BMS, research support from Roche, BMS and Astra Zeneca, Birgitta Hiddinga: None declared, Sjoukje Oosting invited speaker for Merck and Travel Congress Management B.V., advisory board of Bristol Myers Squibb and Genmab; unpaid member of steering and safety monitoring committee of ALX Oncology., research grants form Merck, Novartis, Pfizer; product samples of Celldex, Novartis and Pfizer., Mathilde Jalving advisory board Pierre Fabre, BMS, Astra Zeneca, Albert de Heij: None declared, Daan Knapen: None declared, Geke Hospers consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Roche, MSD, Pfizer, Novartis, Sanofi, Pierre Fabre, search grants from Bristol-Myers Squibb, Seerave.