CD40 blockade shows therapeutic potential in Sjögren's syndrome

The novel anti-CD40 monoclonal antibody iscalimab has demonstrated clinical activity in patients with primary Sjögren's syndrome in a proof-of-concept study.

In the 12-week trial, 12 patients in cohort 1 were randomly assigned to receive either 3 mg/kg iscalimab (n=8) or placebo (n=4) via subcutaneous injections, whereas 32 patients in cohort 2 were randomized to receive either 10 mg/kg intravenous doses of iscalimab (n=21) or placebo (n=11). Treatment was administered at weeks 0, 2, 4 and 8.

Adverse events occurred in all patients in cohort 1, and in 52 percent of those on iscalimab and 64 percent of those on placebo in cohort 2. There were two serious adverse events documented, one was a case of bacterial conjunctivitis in cohort 1 and the other was a case of atrial fibrillation in cohort 2, although both were unrelated to active treatment.

Intravenous iscalimab treatment led to an improvement in clinical activity, as indicated by a mean reduction in European League Against Rheumatism Sjögren's syndrome disease activity index (ESSDAI) score of 5.21 points (95 percent confidence interval, 0.96–9.46) compared with placebo (p=0.0090). ESSDAI scores were similar in subcutaneous iscalimab and placebo arms.

The present data suggest that CD40–CD154 signalling is a key pathway associated with the underlying pathology of primary Sjögren’s syndrome, the researchers said, adding that the therapeutic potential of CD40 blockade in such disease should be further studied.