The New England journal of medicine · 2026
Ianalumab for the Treatment of Patients with Sjögren's Disease.
СтатьяРандомизированное исследованиеМногоцентровое исследованиеКлиническое исследование III фазыНазвание и аннотация: Перевод пока не подготовлен
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Mariette Xavier, Grader-Beck Thomas, Finzel Stephanie, Schiopu Elena, Papas Athena, Devauchelle-Pensec Valerie, Sopala Monika, Zeng Xiaofeng, Noaiseh Ghaith, Takeuchi Tsutomu, Kumar Uma, Hermann Josef, Ozawa Hiroki, Fox Robert, Zong Susan, Narayanswamy Deepak, Li Xiaomei, Luo Wen-Lin, Woznicki Janice, Debonnett Laurie, Zhu Xuan, He Linchen, Matzkies Franziska, Jahreis Angelika, Jain Devendra Kumar, Porter Brian, Lau Carol, Dörner Thomas, McCoy Sara S, Bowman Simon J, Hueber Wolfgang, NEPTUNUS-1 and NEPTUNUS-2 Investigators, NEPTUNUS-1 Investigators, NEPTUNUS-2 Investigators
Аннотация
BACKGROUND: 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, depleting B cells through antibody-dependent cellular cytotoxicity and inhibiting B-cell activation and survival through blockade of B-cell activating factor receptor.
METHODS: We conducted two 52-week, double-blind, randomized, placebo-controlled trials involving patients with active Sjögren's disease. Patients in the NEPTUNUS-1 trial were assigned in a 1:1 ratio to receive subcutaneous ianalumab (300 mg monthly) or placebo; patients in the NEPTUNUS-2 trial were assigned in a 1:1:1 ratio to receive 300 mg of ianalumab monthly or every 3 months or placebo. The primary end point was the change from baseline in the score on the European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) at week 48 (scores range from 0 to 123, with higher scores indicating greater disease activity). The first key secondary end point in the hierarchical plan for the NEPTUNUS-1 trial was an ESSDAI response (≥5-point reduction) at week 48; for the NEPTUNUS-2 trial, it was the change from baseline in the score on the Sjögren's Syndrome Symptom Diary (SSSD) or EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at week 48.
RESULTS: Overall, 275 patients underwent randomization in the NEPTUNUS-1 trial (ianalumab monthly, 137 patients; placebo, 138 patients) and 504 in the NEPTUNUS-2 trial (ianalumab monthly, 168 patients; ianalumab every 3 months, 167 patients; and placebo, 169 patients). In both trials, ianalumab monthly led to a significantly greater decrease in the ESSDAI score at week 48 than placebo, with a between-group difference of -1.3 points (95% confidence interval [CI], -2.6 to 0.0; P = 0.0496) in NEPTUNUS-1 and -1.0 points (95% CI, -2.0 to 0.0; P = 0.04) in NEPTUNUS-2. No significant differences in the incidence of an ESSDAI response or in the change from baseline in SSSD or ESSPRI scores were observed at week 48. The incidence of serious adverse events was similar with ianalumab and placebo. Nonserious local injection-site and systemic injection-related reactions were more common in the ianalumab groups.
CONCLUSIONS: In these two trials involving patients with active Sjögren's disease, ianalumab at a dose of 300 mg monthly resulted in a significantly greater decrease in disease activity at week 48 than placebo, although there were no significant differences in the incidence of an ESSDAI response or in the change from baseline in SSSD or ESSPRI symptom scores. (Funded by Novartis Pharma; NEPTUNUS-1 and NEPTUNUS-2 ClinicalTrials.gov numbers, NCT05350072 and NCT05349214, respectively.).
METHODS: We conducted two 52-week, double-blind, randomized, placebo-controlled trials involving patients with active Sjögren's disease. Patients in the NEPTUNUS-1 trial were assigned in a 1:1 ratio to receive subcutaneous ianalumab (300 mg monthly) or placebo; patients in the NEPTUNUS-2 trial were assigned in a 1:1:1 ratio to receive 300 mg of ianalumab monthly or every 3 months or placebo. The primary end point was the change from baseline in the score on the European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) at week 48 (scores range from 0 to 123, with higher scores indicating greater disease activity). The first key secondary end point in the hierarchical plan for the NEPTUNUS-1 trial was an ESSDAI response (≥5-point reduction) at week 48; for the NEPTUNUS-2 trial, it was the change from baseline in the score on the Sjögren's Syndrome Symptom Diary (SSSD) or EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at week 48.
RESULTS: Overall, 275 patients underwent randomization in the NEPTUNUS-1 trial (ianalumab monthly, 137 patients; placebo, 138 patients) and 504 in the NEPTUNUS-2 trial (ianalumab monthly, 168 patients; ianalumab every 3 months, 167 patients; and placebo, 169 patients). In both trials, ianalumab monthly led to a significantly greater decrease in the ESSDAI score at week 48 than placebo, with a between-group difference of -1.3 points (95% confidence interval [CI], -2.6 to 0.0; P = 0.0496) in NEPTUNUS-1 and -1.0 points (95% CI, -2.0 to 0.0; P = 0.04) in NEPTUNUS-2. No significant differences in the incidence of an ESSDAI response or in the change from baseline in SSSD or ESSPRI scores were observed at week 48. The incidence of serious adverse events was similar with ianalumab and placebo. Nonserious local injection-site and systemic injection-related reactions were more common in the ianalumab groups.
CONCLUSIONS: In these two trials involving patients with active Sjögren's disease, ianalumab at a dose of 300 mg monthly resulted in a significantly greater decrease in disease activity at week 48 than placebo, although there were no significant differences in the incidence of an ESSDAI response or in the change from baseline in SSSD or ESSPRI symptom scores. (Funded by Novartis Pharma; NEPTUNUS-1 and NEPTUNUS-2 ClinicalTrials.gov numbers, NCT05350072 and NCT05349214, respectively.).