Pos0139 Safety and Efficacy of Sulfasalazine in Treatment of Immune Checkpoint Inhibitor-Inflammatory Arthritis

Background: Sulfasalazine (SSZ) has been recommended [1] as a steroid-sparing agent for immune checkpoint inhibitor-inflammatory arthritis (ICI-IA), and this agent is sometimes favored due to its low immunosuppressive effect compared to other DMARDs. However, there is little published data on its efficacy for ICI-IA, and a small case series of four patients published in 2018 raised concerns that SSZ might cause a high rate of hypersensitivity reactions in ICI-IA patients, particularly those receiving anti-PD1 therapy [2]. Objectives: To assess the safety and efficacy of SSZ for ICI-IA. Methods: This is a retrospective observational study of all patients treated by rheumatologists in the Mass General-Brigham system for ICI-IA with SSZ from 1/01/2017-7/01/2023. Outcomes were ascertained by manual chart review. The primary outcome was the occurrence of an adverse event (AE) leading to withdrawal of SSZ therapy. The secondary outcomes were 1) arthritis control defined as grade 1 arthritis with SSZ monotherapy, 2) arthritis control defined as grade 1 arthritis with SSZ and < 5 mg prednisone daily, and 3) failure to achieve grade 1 arthritis without concomitant prednisone dosing in excess of 5 mg daily or requiring further escalation of DMARD therapy. Results: The study included 37 patients with mean age at SSZ initiation of 63.7 years (SD 10.7 years). 22 (59%) patients were male, and 23 (62%) were on ICI therapy for melanoma. 24 (65%) had received PD1/PDL1 monotherapy, 2 (5%) received CTLA4 monotherapy, and 11 (30%) received combination PD1/PDL1-CTLA4 therapy (Table 1). 21 of 37 patients (57%) who were started on SSZ therapy experienced an adverse event (AE) for which the medication was discontinued. Nine patients (24%) experienced a rash and were suspected to have experienced a SSZ hypersensitivity reaction; 8 (22%) of these patients developed a rash within 5 weeks of starting SSZ. One patient required hospitalization for his symptoms, and one other patient required ED evaluation, whereas all other patients were managed in the outpatient setting. All 21 patients with AEs had either received PD1/PDL1 monotherapy or combination therapy. Among these 21 patients, median duration of SSZ therapy was 26 days, and 20 patients were on either 500 mg 2x daily or 1000 mg 2x daily dosing with only one patient receiving 1500 mg 2x daily dosing. Of the 16 patients who tolerated SSZ, only 3 achieved arthritis control without ongoing steroid therapy; 1 additional patient achieved arthritis control while allowing < 5 mg prednisone daily; and 10 failed to achieve arthritis control on SSZ and required escalation of DMARD therapy. Conclusion: In this cohort of 37 ICI-IA patients treated with SSZ, we observed high rates of AEs including hypersensitivity reactions requiring SSZ discontinuation. Our observed rate of AEs is much higher than that observed in patients treated with SSZ for rheumatoid arthritis, approximately 20-30% of whom discontinue the medication due to intolerance [3]. Among those patients who tolerated SSZ, only a small percentage achieved disease control while on SSZ monotherapy. This study adds to data about high rates of SSZ hypersensitivity reactions in ICI-IA patients and also suggests that few patients achieve disease remission while on SSZ monotherapy. REFERENCES: [1] Jeurling S, Cappelli LC. Treatment of immune checkpoint inhibitor-induced inflammatory arthritis. Curr Opin Rheumatol. 2020 May;32(3):315-320. [2] Ford M, et al. High proportion of drug hypersensitivity reactions to sulfasalazine following its use in anti-PD-1-associated inflammatory arthritis. Rheumatology. 2018 Dec;57(12):2244-2246. [3] Plosker GL, Croom KF. Sulfasalazine. Drugs. 2005;65:1825-49. Acknowledgements: NIL. Disclosure of Interests: Gregory Challener: None declared, Minna J. Kohler: None declared, Chio Yokose: None declared, Janeth Yinh Janssen, Hyon Choi ANI, LG, Horizon, Shanton, Protalix, Horizon.