0761: Identification of Outcome Domains in Immune Checkpoint Inhibitor-Induced Inflammatory Arthritis and Polymyalgia Rheumatica: A Scoping Review by the OMERACT IrAE Working Group

Nilasha Ghosh¹, Nina Couette², Wouter van Binsbergen³, Sophia Weinmann⁴, Bridget Jivanelli¹, Beverley Shea⁵, Anne Bass⁶, Karolina Benesova⁷, Clifton O. Bingham III⁸, Cassandra Calabrese⁹, Laura C. Cappelli¹⁰, Karmela Kim Chan¹, Ernest Choy¹¹, Dimitrios Daoussis¹², Susan Goodman¹, Marie Hudson¹³, Shahin Jamal¹⁴, Jan Leipe¹⁵, Maria A. Lopez-Olivo¹⁶, Maria Suarez-Almazor¹⁷, Conny van der Laken¹⁸, Alexa Meara¹⁹, David Liew²⁰ and Marie Kostine²¹, ¹Hospital for Special Surgery, New York, NY, ²Department of Internal Medicine. Division of Rheumatology & Immunology, The Ohio State University, Columbus, OH, ³Amsterdam Rheumatology and Immunology Center, Department of Rheumatology & Clinical Immunology, Amsterdam University Medical Center location DBL, Amsterdam, Netherlands, ⁴Department of Rheumatology & Immunology, Duke University, Durham, NC, ⁵School of Epidemiology and Public Health, University of Ottawa, Ottawa, ⁶Hospital for Special Surgery/Weill Cornell Medicine, New York, NY, ⁷University Hospital Heidelberg, Heidelberg, Germany, ⁸Johns Hopkins University, Baltimore, MD, ⁹Cleveland Clinic Foundation, Cleveland Heights, OH, ¹⁰Johns Hopkins School of Medicine, Baltimore, MD, ¹¹Division of Infection and Immunity, CREATE Centre, Cardiff University, Cardiff, Wales, United Kingdom, ¹²Department of Rheumatology, University of Patras Medical School, Patras University Hospital, Patras, Greece, ¹³McGill University, Montréal, QC, Canada, ¹⁴University of British Columbia, Vancouver, BC, Canada, ¹⁵Division of Rheumatology, Department of Medicine V, University Hospital Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Heidelberg, Germany, ¹⁶The University of Texas, MD Anderson Cancer Center, Houston, TX, ¹⁷MD Anderson Cancer Center, Houston, TX, ¹⁸Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Centers – location VUMC, Amsterdam, Netherlands, ¹⁹The Ohio State University Wexner Medical Center, Columbus, OH, ²⁰Austin Health, Heidelberg, Australia, ²¹Pellegrin Hospital, University Hospital of Bordeaux, Rheumatology, Bordeaux, France

Background/Purpose: Immune checkpoint inhibitors (ICI), increasingly used cancer therapeutics, can cause off-target inflammatory effects called immune-related adverse events (irAEs), including ICI-induced inflammatory arthritis (ICI-induced IA) and polymyalgia rheumatica (ICI-induced PMR). There are no validated classification criteria or outcome measures for these conditions, and adaptation of treatment recommendations from corresponding rheumatic diseases, such as RA, spondyloarthritis and PMR, may not be appropriate. In this study, we aimed to collate clinical descriptors of ICI-induced IA and ICI-induced PMR and aggregated domains used for these conditions in order to inform the development of a core set ­of outcome domains.

Methods: As the initial step of the OMERACT core domain set generation process, we systemically searched Medline (Pubmed), EMBASE, Cochrane, and CINHL through March 2021 to identify all studies that provided both clinical descriptions and domains relevant to ICI-induced IA and ICI-induced PMR. Publications were sorted into groups based on the clinical characterization of the disease. Outcome domains were mapped to core areas, such as pathophysiological manifestations, life impact, resource use, and longevity/survival, as suggested by the OMERACT 2.1 Filter.

Results: We identified 69 publications (Figure 1) which were sorted into seven groups based on clinical descriptors of arthritis/PMR (Table 1). At least one rheumatologist was a co-author in 41 (59%) publications. Over a third of these publications utilized non-specific clinical diagnoses of "arthritis," "arthralgia," and/or "PMR". Other publications provided the number (n=12 publications), the distribution, size and/or names of specific joints affected (n=17 publications), while others labeled the irAE as the corresponding rheumatic disease, such as rheumatoid arthritis or spondyloarthritis (n=9 publications). Outcomes used for ICI-IA and ICI-PMR are listed in Figure 2. Most distinct outcome domains mapped to the pathophysiology/manifestations core area (24 domains), such as signs/symptoms (13 domains), labs (6 domains), and imaging (5 domains), with harm domains of adverse effects from irAE treatment and fear of irAE treatment decreasing ICI efficacy. Forty-three publications also referenced irAE treatment and 35 publications described the subsequent response. Unique to this population, tumor response was an outcome domain used in 32 publications.

Conclusion: There is considerable heterogeneity in the domains used to clinically characterize ICI-induced IA and ICI-induced PMR. Among outcomes, there were several domains mapped to the pathophysiologic manifestations core area, although several publications highlighted domains evenly distributed among the other core areas of life impact, longevity/survival and resource use. Assembling classification criteria specific to ICI-induced IA and PMR in addition to gaining eventual consensus achievement of core areas and domains are next steps in order to study and effectively treat these conditions.
Flow diagram for scoping review study identification

Clinical characterization categories of ICI-induced inflammatory arthritis/PMR

ICI-induced inflammatory arthritis and PMR outcomes mapped to core areas and domains
Disclosures: N. Ghosh, GoodRx, Musculo; N. Couette, None; W. van Binsbergen, Bristol-Myers Squibb(BMS); S. Weinmann, None; B. Jivanelli, None; B. Shea, None; A. Bass, None; K. Benesova, Abbvie, BMS, Gilead/Galapagos, Janssen, Lilly, Medac, MSD, Novartis, Roche, Viatris, Gilead/Galapagos, Novartis, Abbvie, Novartis; C. Bingham III, AbbVie, Janssen, Pfizer, Sanofi, Bristol Myers Squibb, Eli Lilly; C. Calabrese, Sanofi, Astrazenica; L. C. Cappelli, Bristol-Myers Squibb(BMS); K. Chan, None; E. Choy, AbbVie, Bio-Cancer, Biogen, Novartis, Pfizer, Roche, Regeneron, R-Pharm, Gilead, Eli Lilly, Janssen, Chugai Pharma, Biocon, Bristol-Myers Squibb (BMS), Galapagos, Amgen, Celgene, ObsEva, Inmedix, Merck Serono, Novimmune, Sanofi, SynAct Pharma, UCB; D. Daoussis, None; S. Goodman, Novartis, UCB; M. Hudson, Bristol-Myers Squibb(BMS), Boehringer-Ingelheim, Mallinckrodt; S. Jamal, AbbVie/Abbott, Amgen, Bristol-Myers Squibb(BMS), Eli Lilly, Merck/MSD, Pfizer, Janssen, Roche, UCB; J. Leipe, None; M. Lopez-Olivo, None; M. Suarez-Almazor, Eli Lilly, Pfizer, Celgene, ChemoCentryx, Gilead; C. van der Laken, None; A. Meara, None; D. Liew, None; M. Kostine, Bristol-Myers Squibb(BMS), Merck/MSD, Novartis, Janssen, Biogen.