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Les thérapies ciblées pour les effets indésirables graves liés à l'immunité des inhibiteurs [...]

Sedmak N, Sebbag E, Loc PTB, Fabacher T, Bahougne T, Arnold C, et al. Congrès EULAR 2023, OP0270 (Mai 2023)

Background : In about 10% of patients, the immune response to immune checkpoint inhibitors (ICI) exceeds the anti-tumor response and leads to autoimmune complications (immune-related Adverse Events, irAEs), which can sometimes be severe and require the use of targeted therapies. Two studies recently reported a deleterious impact of targeted therapies on the survival of patients with irAEs.

Objectives : To compare overall survival in patients treated or not with a biological or targeted synthetic DMARD (b/tsDMARD) for an hospitalized irAE.

Methods : All adults included in the French national health database who initiated an ICI between 2014 and 2019, for any type of cancer, were retrospectively analyzed. Follow-up was analyzed between 2013 to 2020, to have a one-year look-back and one year look-ahead period. The occurrence of an irAE during ICI treatment or in the 12 months after its last administration was defined by the combination of (1) hospitalization for a cause evoking an irAE of any nature, except endocrinopathy, and (2) either the discontinuation of the ICI, or the initiation of corticosteroids, or of a conventional DMARD or a b/tsDMARD, or a new recognition as a long-term disabling condition (LTD) for an autoimmune or inflammatory disease. Patients with irAE treated with b/tsDMARD were matched (1:3) at the time they initiated b/tsDMARD to those who did not initiate b/tsDMARD, using a dynamic propensity score calculated every 30 days. The propensity score included gender, age, type of cancer, type of ICI, time from cancer to initiation of ICI and from initiation of ICI to irAE, use of corticosteroids, hospitalization in intensive care unit, type of irAE, number of LTDs, Charlson’s index and FDep social deprivation index. Overall survival was compared between the two groups using a Cox model. A sensibility analysis restricted to gastrointestinal and rheumatic irAEs was performed.

Results : 71,723 patients (men: 66.0%, median age: 66 years) initiating an ICI were analyzed. An hospitalized irAE occurred in 7883 patients (11.0%). irAE occurred at a median time of 72 days after ICI initiation, and the 4 more frequent were gastrointestinal (inflammatory colitis, 4.7%), cardiologic (2.0%), rheumatic (1.8%), and pulmonary (1.7%). Median patient follow-up after irAE was 356 days. Mortality after irAE was 4.8% at 1 month and 11.3% at 3 months. After matching, 325 patients were treated for an irAE with a b/tsMDARD (Infliximab (57.7%), Rituximab (25.5%), Tocilizumab (4.2%), Vedolizumab (3.3%), others (9.3%)), including 257 and 40 for a gastrointestinal or rheumatic irAE, respectively. They were compared to 975 patients who were not treated with a b/tsDMARD. The median time from ICI initiation to irAE was well balanced by matching (93 versus 92 days, respectively). ICI was discontinued in 25.4% of b/tsDMARD treated patients patients within 3 months after the irAE, compared to 20.9% in the group not treated with a b/tsDMARD. Mortality after irAEs was 6.8% and 7.6% at 3 months, respectively, and 16.0% and 17.9% at 6 months, respectively. Overall survival whatever the type of irAE did not significantly differ in patients treated with or without a b/tsDMARD (HR=0.87, CI=[0.74, 1.03]), or in patients treated for a rheumatic irAE (HR=0.80, CI=[0.51, 1.25]). Overall survival was significantly improved in gastrointestinal irAE in patients treated with a b/tsDMARD compared to patients not treated with a b/tsDMARD (HR=0.80, CI=[0.66, 0.97]).

Conclusion : In one of the largest study to date in terms of number of hospitalized irAEs and number of b/tsDMARD-treated patients, targeted therapies were not associated with a worse prognosis and significantly improved overall survival in patients with induced colitis, the most frequent and one of the most severe irAEs.

(Communication Orale) Sedmak N, Sebbag E, Loc PTB, Fabacher T, Bahougne T, Arnold C, et al. Targeted Therapies for Severe Immune-Related Adverse Events of Immune Checkpoint Inhibitors Are Not Associated with a Worse Prognosis. Annals of the Rheumatic Diseases 2023;82:178–178.


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