1. Isaclimab significantly improved disease activity at 150 mg and 600 mg doses.

2. Adverse events were comparable between cohorts with no deaths reported.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Sjögren’s disease is a chronic autoimmune condition with limited targeted treatment. This randomized controlled trial aimed to assess whether iscalimab, an anti-CD40 monoclonal antibody, could reduce disease activity and improve patient-reported symptoms in patients with active Sjögren’s disease. The primary outcome of this study was dose-response relationship of iscalimab on the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), while key secondary outcome was the effect of iscalimab 600 mg on patient-reported symptoms using the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI). According to study results, iscalimab significantly reduced disease activity at 150 mg and 600 mg doses. Although this study was well done, it was limited by its short duration and small sample sizes.

Click to read the study in The Lancet

Relevant Reading: Efficacy and safety of iscalimab, a novel anti-CD40 monoclonal antibody, in moderate-to-severe myasthenia gravis: A phase 2 randomized study

In-depth [randomized controlled trial]: Between Oct 1, 2019, and Feb 28, 2022, 460 patients were assessed for eligibility across 71 sites in 23 countries. Included were patients ≥18 years with Sjögren’s disease who met the 2016 ACR/EULAR criteria, had moderate-to-high disease activity based on ESSDAI and ESSPRI scores, and were randomized into either dose-ranging or proof-of-concept cohorts. Altogether, 273 patients (173 in cohort 1 [43 placebo; 44 iscalimab 150 mg; 43 iscalimab 300 mg; 43 iscalimab 600 mg] and 100 in cohort 2 [50 placebo; 50 iscalimab 600 mg]) were included in the final analysis. Cohort 1 demonstrated a significant dose-response relationship, with iscalimab showing statistically significant improvements in disease activity at the 150 mg (ESSDAI mean difference -3.0%, p=0.0025) and 600 mg (-0.57%, p=0.12) doses versus placebo. Serious adverse events were comparable in both cohorts (9 of 173 for cohort 1 vs. 4 of 100 for cohort 2; no deaths reported). Findings from this study suggest that iscalimab is well-tolerated and offers promising benefits in Sjögren’s disease.

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