Combotherapies in immune-mediated inflammatory diseases: A study using the Clinical Data Warehouse from Paris Hospitals’ Public Assistance

Abstract

Background

The combination of different biological and targeted synthetic DMARDs (i.e., combotherapy) has recently emerged in the management of immune-mediated inflammatory diseases (IMID). However, real-life data across specialities and prognostic factors related to combotherapy are lacking.

Methods

Multicenter observational study conducted using the Clinical Data Warehouse from Paris Hospitals’ Public Assistance including IMID patients under combotherapy, and a matched monotherapy control group. The primary endpoint was the occurrence of serious adverse events (SAE), defined by severe infections, major cardiovascular events, neoplasia and mortality (all-cause).

Results

From 42,071 subjects having an IMID, 131 combotherapy lines were identified among 125 patients (median age of 36 years, 58 % females) between 2017 and 2022. The most frequent IMIDs were inflammatory bowel disease (48.8 %), connective tissue diseases (23.2 %), inflammatory myopathies (14.4 %) and vasculitis (11.2 %). After a median follow-up of 15 months [IQR 19], 30 (24 %) patients presented severe infections, 5 (4 %) neoplasia, 4 (3.2 %) venous thromboembolism, 3 (2.4 %) acute coronary syndromes and 7 (5.6 %) deaths. The 1-year cumulative incidence of SAE and severe infections were 29 % (95 %CI 21–38), and 24 % (95 %CI 16–32), respectively. The survival, incidence of SAE and severe infections were not statistically different from combotherapy patients compared to monotherapy controls (n=251) after adjustment for confounders. In multivariate analyses, we found abatacept + JAKi (HR 6.81, 95 %CI 1.88–24.68), anti-IL-1-based (HR 4.82, 95 %CI 1.17–19.89) and anti-CD20-based (HR 4.03, 95 %CI 1.22–13.31) combotherapies to be independently associated with an increased risk of SAE.

Conclusion

The overall risk of SAE under combotherapy does not seem greatly increased compared to monotherapy, but certain combinations warrant caution. The combotherapy composition seems predictive of safety outcomes.