ObjectivesTo compare the safety and effectiveness of biologic and conventional disease-modifying antirheumatic drugs (DMARDs) for immune checkpoint inhibitor-associated inflammatory arthritis (ICI-IA).MethodsThe retrospective multicentre observational study included patients with a diagnosis of ICI-IA treated with a tumour necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL6Ri) and/or methotrexate (MTX); patients with pre-existing autoimmune disease were excluded. The primary outcome was time to cancer progression from ICI initiation; the secondary outcome was time to arthritis control from DMARD initiation. Cox proportional hazard models were used to compare medication groups, adjusting for confounders.Results147 patients were included (mean age 60.3 (SD 11.9) years, 66 (45%) women). ICI-IA treatment was TNFi in 33 (22%), IL6Ri 42 (29%) and MTX 72 (49%). After adjustment for time from ICI initiation to DMARD initiation, time to cancer progression was significantly shorter for TNFi compared with MTX (HR 3.27 (95% CI 1.21 to 8.84, p=0.019)) while the result for IL6Ri was HR 2.37 (95% CI 0.94 to 5.98, p=0.055). Time to arthritis control was faster for TNFi compared with MTX (HR 1.91 (95% CI 1.06 to 3.45, p=0.032)) while the result for IL6Ri was HR 1.66 (95% CI 0.93 to 2.97, p=0.089). A subset analysis in patients with melanoma gave similar results for both cancer progression and arthritis control.ConclusionThe treatment of ICI-IA with a biologic DMARD is associated with more rapid arthritis control than with MTX, but may be associated with a shorter time to cancer progression.
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.
BackgroundImmune checkpoint inhibitor associated arthritis (ICI-A) commonly persists for months to years, even after ICI cessation.[1]ObjectivesTo compare the safety and effectiveness of biologic and conventional disease modifying anti-rheumatic drugs (DMARDs) for ICI-A.MethodsRetrospective multicenter observational study. Inclusion: 1) diagnosis of ICI-A and 2) treatment with a tumor necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL6Ri) and/or methotrexate (MTX). Exclusion: preexisting autoimmune disease. The primary outcome was time to cancer progression from ICI initiation. Patients whose cancer progressed prior to DMARD initiation were excluded from this analysis. The secondary outcome was time to arthritis control from DMARD initiation, defined as grade 1 arthritis and prednisone ≤10mg/day. Cox proportional hazard models were generated, adjusting for confounders. A sensitivity analysis was performed incorporating a time dependent variable “time from ICI initiation to DMARD initiation.”Results147 patients were included, mean (SD) age 60.3 (11.9) years, 66 (45%) females. Sixty percent had received PD1/PDL1 monotherapy, 30% received combination CTLA4/PD1. Eighty percent had stage IV cancer. ICI-A treatment was TNFi in 33 (22%), IL6Ri 42 (29%), MTX 72 (49%) (Table 1). A Kaplan-Meier curve showing time to cancer progression by DMARD is shown inFigure 1. In an unadjusted Cox model with MTX as the reference, time to cancer progression with a TNFi was HR 2.51 (95% CI 0.91-6.93, p=0.075) and for IL6Ri HR 2.36 (95% CI 0.91-6.12, p=0.078). After adjustment for the time dependent variable, time to cancer progression was significantly shorter for TNFi-treated patients compared to MTX, HR 3.27 (95% CI 1.21-8.84, p=0.019). The result for IL6Ri was HR 2.31 (95% CI 0.98-5.41, p=0.055). Time to arthritis control was significantly faster for TNFi compared to MTX, HR 1.91 (95% CI 1.06-3.45, p=0.032) in an adjusted Cox model. Results for IL6Ri were HR 1.66 (95% CI 0.93-2.97, p=0.089). Results for cancer progression and arthritis control were similar in the subset of patients with melanoma.ConclusionTreatment of ICI-A with biologic DMARDs is associated with more rapid arthritis control than with MTX but may be associated with a shorter time to cancer progression. A prospective randomized controlled trial is needed to verify these findings and to identify the optimal approach to managing patients with high grade ICI-A.Reference[1] Braaten TJ, et al Ann Rheum Dis. 2020 Mar;79(3):332-338.Table 1.Patient characteristicsTotalTNFiIL6RMTXp-valueN147 (100%)33 (22%)42 (29%)72 (49%)Age, mean (SD)60.3 (11.9)56.3 (14.0)61.5 (12.5)61.5 (10.1)0.085Sex (female)66 (45%)13 (39%)15 (36%)38 (53%)0.17Race (white)136 (92%)30 (91%)40 (95%)66 (92%)0.18Cancer type0.068Melanoma63 (43%)16 (48%)21 (50%)26 (36%)Non-small cell lung cancer15 (10%)1 (3%)0 (0%)14 (19%)Renal cell carcinoma24 (16%)5 (15%)12 (29%)7 (10%)Bladder cancer7 (5%)1 (3%)3 (7%)1 (4%)Other38 (25%)10 (30%)6 (14%)22 (31%)Cancer stage0.34III26 (18%)7 (21%)6 (14%)13 (18%)IV118 (80%)24 (73%)36 (86%)58 (81%)Checkpoint inhibitor0.91PD1/PDL1 monotherapy101 (69%)24 (73%)28 (67%)49 (68%)Combination (CTLA4/PD1)44 (30%)9 (27%)13 (31%)22 (31%)ICI discontinued for arthritis58 (40%)12 (36%)17 (40%)29 (40%)0.92ICI initiation to DMARD start (days), median (IQR)403 (258,638)411 (284, 622)300 (170, 435)486(258, 675)0.020Duration of DMARD treatment, median (IQR)278 (77, 546)92 (45, 149)309 (63, 483)420 (138, 765)<0.001Maximum glucocorticoid dose, mean (SD)40 (27)53 (27)42 (28)33 (23)0.002Figure 1.Kaplan-Meier curve showing time to cancer progression from time of immune checkpoint inhibitor initiationAcknowledgements:NIL.Disclosure of InterestsAnne Bass: None declared, Noha Abdel-Wahab Speakers bureau: ChemoCentryx, Consultant of: ChemoCentryx, Pankti Reid: None declared, Jeffrey Sparks Consultant of: Bristol Myers Squibb, AbbVie, Amgen, Boehringer Ingelheim, Gilead, Inova Diagnostics, Janssen, Optum, Pfizer, Grant/research support from: Bristol Myers Squibb, cassandra calabrese Speakers bureau: Sanofi, Consultant of: Astazenica, Deanna Jannat-Khah: None declared, Nilasha Ghosh: None declared, Divya Rajesh: None declared, Carlos Aude: None declared, Lydia Gedmintas: None declared, Lindsey MacFarlane: None declared, Senada Arabelovic: None declared, Adewunmi Falohun: None declared, Komal Mushtak: None declared, Farah Al Haj: None declared, Adi Diab: None declared, Ami Shah Grant/research support from: Eicos Sciences, Medpace LLC, Arena Pharmaceuticals, Kadmon Corporation, Clifton Bingham Consultant of: Bristol Myers Squibb,: Abbvie, Janssen, Lilly, Pfizer, Sanofi, Moderna, Grant/research support from: Bristol Myers Squibb, Karmela Kim Chan: None declared, Laura Cappelli Consultant of: Bristol Myers Squibb, Grant/research support from: Bristol Myers Squibb.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.