Is Combo DMARD Therapy Safe for Inflammatory Diseases?

TOPLINE:

The incidence of serious adverse events did not differ significantly between combo therapy and monotherapy in patients with immune-mediated inflammatory diseases. However, specific combinations such as abatacept with Janus kinase (JAK) inhibitors may be associated with increased risks.

METHODOLOGY:

• Researchers conducted an observational study using the health data repository from the largest hospital in Europe to describe the real-life use and safety concerns of combo therapies in several immune-mediated inflammatory diseases.
• They included 125 patients with immune-mediated inflammatory diseases (median age, 36 years; 58% women) who received 131 combo therapies (defined as at least two concomitant biologic disease-modifying antirheumatic drugs [DMARDs] and/or targeted synthetic DMARDs for ≥ 90 consecutive days).
• Frequently occurring immune-mediated inflammatory diseases were inflammatory bowel disease (48.8%), followed by connective tissue diseases (23.2%), inflammatory myopathies (14.4%), and vasculitis (11.2%).
• Patients were matched with 251 control patients receiving monotherapy.
• The primary endpoint was the occurrence of serious adverse events, including severe infections, major cardiovascular events, neoplasia, and all-cause mortality.

TAKEAWAY:

• After a median follow-up duration of 15 months, 85 patients (68%) on combo therapy did not experience any serious adverse events, and 30 patients experienced 54 episodes of severe infections; seven patients died.
• The 1-year cumulative incidence rates of serious adverse events and serious infections were not significantly different between combo therapy and monotherapy groups after adjustment for glucocorticoid intake and previous history of infections.
• Patients who received combo therapy containing tumor necrosis factor (TNF) inhibitors had a higher risk for severe infections than control patients who received monotherapy with TNF inhibitors (1-year incidence rate, 22.2% vs 7%; P = .039). Similar findings were noted for the risk for serious adverse events with JAK inhibitors in the combo therapy group vs the monotherapy group (P = .027).
• Specific combo therapies such as abatacept with JAK inhibitors (hazard ratio [HR], 6.81; P < .01) and anti–interleukin 1–based (HR, 4.82; P = .03) and anti-CD20–based therapies (HR, 4.03; P = .02) were associated with a significantly increased risk for serious adverse events.

IN PRACTICE:

“The underlying disease and the agents being combined are among the relevant variables to be considered when individually choosing a combo therapy. Nevertheless, well-documented prognostic factors that could guide this decision are yet to be clarified,” the authors wrote. “Our data should help clinicians from a wide range of specialties in the management of such complex patients,” they added.

SOURCE:

This study was led by Anne-Laure Gérard and Matheus Vieira , Sorbonne Universités, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Centre national de références Maladies Autoinflammatoires rares et Amylose inflammatoire in Paris, France. It was published online on February 14, 2025, in Seminars in Arthritis and Rheumatism.

LIMITATIONS:

The study’s reliance on hospital prescription data might have led to the underestimation of out-of-hospital events. The 90-day definition of combo therapy might have overlooked serious adverse events leading to early discontinuation. The median follow-up duration of 15 months was likely insufficient to assess the onset or recurrence of neoplasia, potentially underestimating rare or late-occurring adverse events.

DISCLOSURES:

The study did not report any specific funding source. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.