What it is
Sjögren's disease is a complex, systemic autoimmune disease with no approved targeted therapies. Ianalumab is an IgG1 monoclonal antibody with a dual mechanism of action: it depletes B cells through antibody-dependent cellular cytotoxicity and inhibits B-cell activation and survival by blocking the B-cell activating factor receptor. The authors ran two 52-week, double-blind, randomized, placebo-controlled trials in patients with active Sjögren's disease. NEPTUNUS-1 randomized 275 patients to subcutaneous ianalumab 300 mg monthly or placebo, and NEPTUNUS-2 randomized 504 patients to 300 mg monthly, 300 mg every 3 months or placebo. The primary end point was the change from baseline at week 48 in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI, scored from 0 to 123, higher meaning more disease activity). In both trials monthly ianalumab lowered the ESSDAI significantly more than placebo, with between-group differences of -1.3 points (95% CI, -2.6 to 0.0; P = 0.0496) in NEPTUNUS-1 and -1.0 point (95% CI, -2.0 to 0.0; P = 0.04) in NEPTUNUS-2. There were no significant differences at week 48 in the incidence of an ESSDAI response (a reduction of 5 points or more) or in the change in patient-reported symptom scores (the Sjögren's Syndrome Symptom Diary or the EULAR Sjögren's Syndrome Patient Reported Index). Serious adverse events were similar with ianalumab and placebo, while nonserious injection-site and injection-related reactions were more common with ianalumab. The trials were funded by Novartis Pharma.
Why it matters
In two placebo-controlled trials in Sjögren's disease, monthly ianalumab cut a 0-to-123 activity score 1.3 and 1.0 points more than placebo, but not symptom scores. Sjögren's disease has no approved targeted therapy, and ianalumab both depletes B cells and blocks the B-cell activating factor receptor. Both trials met their primary end point, with confidence intervals reaching zero (-2.6 to 0.0 and -2.0 to 0.0), while the share of patients whose score fell by 5 points or more and the patients' own symptom scores did not differ significantly from placebo at week 48. Serious adverse events were similar with ianalumab and placebo; injection reactions were more common with the drug.
Underlined numbers link to their source. Every metric and quoted figure is listed under Sources and data below.
Filed underSalivary Gland Disorders and Functions, Ocular Surface and Contact Lens, Systemic Lupus Erythematosus Research
