TOPLINE:

Multitargeted therapy using two biologics or one biologic combined with one JAK inhibitor showed effectiveness in select pediatric patients with refractory immune-mediated inflammatory diseases (IMIDs), with more than 50% reporting remission. However, nearly 70% experienced adverse events such as cytopenia, and more than 25% required hospitalization for infections.

METHODOLOGY:

• Researchers retrospectively analyzed a cohort of 29 pediatric patients with various refractory IMIDs (median age at disease onset, 7 years) who received multitargeted therapy at multiple centers to evaluate the therapy’s safety and glucocorticoid-sparing potential.
• They included 12 patients with inflammatory bowel disease, nine with juvenile idiopathic arthritis (JIA) including eight with systemic JIA and one with polyarticular JIA, six with inborn errors of immunity, and two with connective tissue disease.
• Patients had a median disease duration of 28 months at therapy initiation and had previously received a median of three immunosuppressive drugs.
• Ustekinumab (n = 12) and tofacitinib (n = 11) were the most commonly used drugs in multitargeted therapy regimens and were generally administered at standard doses. The median duration on therapy was 14 months, totaling 499 patient-months of treatment exposure.

TAKEAWAY:

• Overall, 69.0% of patients presented with cytopenia during multitargeted therapy , which was transient in 75.0% of those affected and generally mild to moderate in severity. Infections led to hospitalizations among 27.6% of patients, with a median length of stay of 4 days.
• Of the 15 patients who received systemic glucocorticoids at initiation of multitargeted therapy, 10 discontinued and five achieved tapering to 0.05-0.25 mg/kg/d, with a mean reduction of 0.89 mg/kg/d.
• Clinical remission was reported by treating physicians in 55.2% of patients, partial response in 27.6%, and no response in 17.2%, with an estimated retention rate of 55.4% at 3 years.
• Dose adjustments among those who continued multitargeted therapy included tapering of targeted drugs in six of 18 patients and dose increases in three of 18 at the final visit; additionally, immunomodulators were stopped or their dose was reduced in selected cases.

IN PRACTICE:

“[Multitargeted therapy] can be effective in select patients with refractory IMIDs, although associated with a significant infectious risk. The risk/benefit balance of this emerging therapeutic avenue warrants further investigation, ideally compared with other strategies used in refractory IMIDs (ie, stem cell transplant and bispecific antibodies),” the authors wrote.

SOURCE:

The study was led by Clément Triaille, MD, PhD, CHU Sainte-Justine, Université de Montréal, Montréal, Quebec, Canada. It was published online on February 11, 2026, as a letter in Annals of the Rheumatic Diseases.

LIMITATIONS:

No limitations were discussed in the letter.

DISCLOSURES:

One author reported receiving partial support from WBI World (Bourses d’excellence, Wallonie-Bruxelles International) and Fondation CHU Sainte-Justine. The authors declared having no competing interests.

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