BackgroundImmune checkpoint inhibitors (ICI) stimulate the immune system to treat cancer but may cause flares of pre-existing immune-mediated diseases such as rheumatoid arthritis (RA). Disease-modifying antirheumatic drugs (DMARDs) used to treat RA may attenuate ICI efficacy. Studies suggest that experiencing flare of a pre-existing disease after ICI may portend a mortality benefit, but no studies have examined whether RA flare after ICI initiation is associated with mortality.ObjectivesTo describe the management and outcomes of patients with pre-existing RA after ICI initiation for cancer.MethodsRetrospective cohort study of patients with pre-existing RA initiating ICI for cancer treatment at Dana-Farber Cancer Institute and Mass General Brigham in Boston, MA, USA (April 2011 to April 2022). Included patients: 1) RA diagnosis code prior to ICI initiation, 2) Met 2010 ACR/EULAR RA criteria by record review. We performed medical record review for data on demographics, cancer, RA disease activity/flares after ICI initiation, DMARDs, ICI disruption, and mortality. We described DMARDs at ICI initiation and for treatment of RA flares. We examined whether RA flare after ICI initiation was associated with mortality using Cox regression in a landmark analysis of those who survived at least 3 months after ICI initiation.ResultsAmong 11,901 patients who initiated ICI for cancer treatment, 100 pre-existing RA patients were included (mean age 70.3 years, 63% female, 89% on PD-1 monotherapy, 50% lung cancer). At ICI initiation, 82% had remission/low RA disease activity, 24% were on glucocorticoids (median prednisone dose 10 mg/day), 35% on conventional DMARDs and 10% on biologic DMARDs (Table 1). None discontinued glucocorticoids and 3/35 (9%) discontinued DMARDs in anticipation of starting ICI. RA flare after ICI occurred in 46/100 (46%,Figure 1) (grade 1 in 16/46 [35%], grade 2 in 25/46 [54%], grade 3 in 5/46 [11%]; 2/46 [4%] required hospitalization for RA flare); 15/46 (33%) that flared had a concomitant immune-related adverse event. RA flares occurred a median of 7 days (IQR 4, 21), usually after the first ICI infusion (ICI cycle IQR 1, 3). RA flares were treated with glucocorticoids (36/46, 78%), often prescribed by oncologists (19/36, 53%), and median initial prednisone dose was 20 mg/day. Treatments of RA flares included DMARDs (19/46, 41%), NSAIDs (12/46, 26%), and intra-articular glucocorticoid injections (5/46, 11%). DMARDs used to treat RA flare included: methotrexate (6/19, 32%), TNF inhibitors (4/19, 21%), hydroxychloroquine (3/19, 16%), sulfasalazine (2/19, 11%), and rituximab (1/19, 5%). ICI was paused or discontinued due to RA flare in 6/46 (13%). Among those who survived at least 3 months, RA flare was not associated with mortality (adjusted hazard ratio 1.24, 95%CI 0.71-2.16).ConclusionIn this largest study to date of patients with pre-existing RA initiating ICI, 46% flared, often after initial ICI infusion, but were mostly mild and managed with typical therapies. A minority had severe RA flares requiring disruption of ICI, but RA flares were not associated with mortality. These results reiterate that pre-existing RA should not be considered a contraindication to ICI treatment for cancer.Table 1.Characteristics at index date of immune checkpoint inhibitor initiation.Pre-existing RA patients (n=100)Mean age, years (SD)70.3 (10.6)Female sex63%PD-1/PD-L1 monotherapy93%CTLA-4 and combination7%Lung cancer50%Melanoma20%Genitourinary tract cancer9%Median RA duration, years (IQR)9.4 (4.8, 17.4)Seropositive59/83 (71%)Most recent disease activityRemission/low63/77 (82%)Moderate/high14/77 (18%)Glucocorticoid24%Hydroxychloroquine15%Sulfasalazine/leflunomide11%Methotrexate9%Rituximab5%IL-6 receptor inhibitors2%Tumor necrosis factor inhibitors/tofacitinib3%Figure 1.Cumulative incidence curve of rheumatoid arthritis flare after initiation of immune checkpoint inhibitor for cancer treatment among patients with pre-existing rheumatoid arthritis (n=100)REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsSenada Arabelovic: None declared, Kaitlin McCarter: None declared, Taylor Wolfgang: None declared, Xiaosong Wang: None declared, Kazuki Yoshida Consultant of: Received consulting fees from OM1, Inc., Emily Banasiak: None declared, Grace Qian: None declared, Emily Kowalski: None declared, Kathleen Vanni: None declared, Nicole LeBoeuf Consultant of: Dr. LeBoeuf receives consulting fees from Bayer, Seattle Genetics, Sanofi, Silverback, and Synox Therapeutics outside the submitted work., Elizabeth Buchbinder: None declared, Lydia Gedmintas: None declared, Lindsey MacFarlane: None declared, Deepak Rao: None declared, Nancy Shadick Grant/research support from: Dr. Shadick is supported by Mallinckrodt, Lilly, BMS, AMGEN, ABBVIE, Aqtual., Ellen Gravallese: None declared, Jeffrey Sparks Consultant of: Dr. Sparks has received research support from Bristol Myers Squibb and performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer unrelated to this work., Grant/research support from: Dr. Sparks has received research support from Bristol Myers Squibb and performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer unrelated to this work.
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