Open-Label, Single-Arm 52‑Week Study of Subcutaneous Anifrolumab 120 mg Weekly in Immunosuppressant‑Naïve and Biologic‑Naïve Systemic Lupus Erythematosus Patients

The primary objective is to evaluate the proportion of immunosuppressant‑naïve and biologic‑naïve participants with Systemic lupus erythematosus who achieve DORIS remission while receiving antimalarial therapy with or without glucocorticoids and subcutaneous anifrolumab 120 mg weekly. Secondary objectives include: assessment of low‑level disease activity using Lupus Low Disease Activity State (LLDAS) and LLDAS‑5; quantification of time spent in DORIS remission, LLDAS or LLDAS‑5; determination of the proportion maintaining these states to week 52 and across ≥3 consecutive visits; measurement of time to attain and sustain DORIS, LLDAS or LLDAS‑5; evaluation of daily glucocorticoid dose at weeks 40 and 52 and its maintenance; analysis of percentage glucocorticoid reduction from week 4 to 40 and its persistence to week 52; calculation of cumulative glucocorticoid exposure from baseline to week 52; assessment of DORIS‑0 attainment; recording time to first moderate‑to‑severe flare; monitoring changes in active cutaneous manifestations, joint activity, health‑related quality of life and fatigue.

In total, 178 individuals meeting the specified enrollment criteria were included. Participants were aged 18 to 70 years and comprised both males and females. All subjects had a confirmed diagnosis of Systemic lupus erythematosus for at least 12 weeks, satisfying the 2019 EULAR/ACR classification criteria, and were ANA‑positive (titer ≥ 1:80) or demonstrated anti‑dsDNA or anti‑Smith antibodies at screening. Each participant was receiving the standard therapeutic regimen of antimalarials with or without oral glucocorticoids and was either IS‑naïve and biologic‑naïve or met the disease activity thresholds of a clinical SLEDAI‑2K score ≥ 4 or, if lower, a glucocorticoid dose ≥ 7.5 mg/day (prednisone equivalent) at baseline. The study population was selected from patients meeting these clinical and laboratory parameters, with no additional lifestyle restrictions reported. The trial’s primary focus was the attainment of DORIS remission in this cohort following initiation of anifrolumab.

The study is a multinational, interventional, phase 5, open‑label, single‑arm trial evaluating subcutaneous anifrolumab 120 mg administered once weekly for 52 weeks in participants with Systemic lupus erythematosus who are naïve to immunosuppressants and biologics and are receiving standard antimalarial therapy with or without glucocorticoids. After informed consent, a screening visit confirms eligibility criteria, including diagnosis per 2019 EULAR/ACR criteria and ANA positivity. Eligible participants proceed to a baseline visit where the first dose is administered and baseline disease activity, laboratory parameters, and safety assessments are recorded. Subsequent study visits are scheduled at regular intervals (e.g., weeks 4, 12, 24, 28, 36, and 52) to monitor adverse events, conduct physical examinations, obtain laboratory samples, and evaluate efficacy outcomes such as the primary endpoint of DORIS remission at week 52 and secondary disease‑activity measures. The end‑of‑study visit at week 52 includes final efficacy and safety evaluations and study drug discontinuation. Participant involvement therefore spans approximately 53 weeks, including screening. Early termination may occur for reasons such as withdrawal of consent, emergence of serious adverse events, requirement for prohibited concomitant medication, pregnancy, or significant protocol non‑compliance.

The investigational product, Saphnelo 120 mg solution for injection in a pre‑filled syringe, contains the monoclonal antibody anifrolumab. Each dose consists of 120 mg of active substance administered by subcutaneous injection once weekly for the 52‑week study period in participants with Systemic Lupus Erythematosus who are immunosuppressant‑naïve and biologic‑naïve.

Background therapy permitted in the trial includes standard antimalarial agents, such as hydroxychloroquine, with optional low‑dose glucocorticoids at the investigator’s discretion. No placebo or alternative biologic comparator is employed.

Study drug is supplied in single‑use pre‑filled syringes and may be administered by qualified study personnel or self‑administered after appropriate training. Dosing records are captured in electronic case report forms, and adherence is monitored through patient diaries and periodic drug accountability checks. The protocol allows dose withholding or delay for safety reasons according to predefined criteria.

Efficacy will be evaluated primarily by the proportion of participants achieving DORIS remission at Week 52. Secondary efficacy assessments include the proportion of participants meeting LLDAS or LLDAS‑5 criteria at Weeks 28 and 52, the cumulative proportion of time participants spend in each remission state, and the proportion achieving sustained remission through all subsequent visits to Week 52 or for three or more consecutive visits. Time to first achievement of each remission state that persists through Week 52 will also be recorded.

Assessments will be conducted at baseline and at scheduled study visits, specifically at Weeks 28 and 52, with additional evaluations at each interim visit to determine sustained remission status. Remission status will be classified according to the predefined DORIS, LLDAS, and LLDAS‑5 definitions. Data will be collected at each visit, aggregated, and analyzed to calculate the proportion of participants meeting each endpoint, the duration of remission, and time‑to‑event outcomes using appropriate statistical methods for a single‑arm, open‑label study.