ACR CONVERGENCE 2021—Using pooled data from the TULIP-1 and TULIP-2 clinical trials, researchers set out to identify whether more patients with systemic lupus erythematosus (SLE) being treated with anifrolumab achieved a low disease activity state than patients with SLE who received placebo.1-3 An analysis of the data was presented at ACR Convergence 2021 by Eric Morand, MD, head of the School of Clinical Sciences, Monash University, and director of Rheumatology, Monash Health, Melbourne, Australia.
Anifrolumab is a type I interferon receptor antagonist.3 On July 30, 2021, the U.S. Food & Drug Administration (FDA) approved anifrolumab for the treatment of adults with moderate to severe SLE who were also receiving standard therapy.4,5 (Note: See below for how this was defined.) The FDA approval was based on both TULIP trials.
The phase 3 TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) studies were randomized, placebo-controlled, 52-week trials during which 300 mg of intravenous anifrolumab was given every four weeks for 48 weeks to eligible patients with moderate to severe SLE despite standard therapy (i.e., treatment with at least one of the following agents or classes: oral glucocorticoids; antimalarials; and/or immunosuppressive agents, such as methotrexate, azathioprine and/or mycophenolate mofetil).
The study included patients classified as having SLE according to the ACR’s 1997 criteria. All patients were at least 18 years old and had moderate to severe disease, with an SLE Disease Activity Index 2000 (SLEDAI-2K) score of at least 6 points, organ-level involvement based on the British Isles Lupus Assessment Group (BILAG) assessment and a Physician’s Global Assessment (PGA) score of at least 1. During the studies, patients continued their existing SLE therapy at stable doses, except for patients receiving oral glucocorticoids, which were tapered.
The BILAG index is a standardized SLE disease activity assessment. Efficacy in the TULIP trials was demonstrated using the BILAG-based Combined Lupus Assessment (BICLA) response, which includes reducing all severe or moderately severe disease activity, no worsening in other organ systems, no worsening in disease activity, no discontinuation of the trial intervention and no use of restricted medications beyond those allowed in the protocol.
Pooled data for the 300 mg of anifrolumab (n=360) and placebo (n=366) groups were analyzed by time point for achieving a lupus low disease activity state (LLDAS), defined as:
- An SLEDAI-2K score of 4 or less without major organ activity;
- No new disease activity;
- A PGA score (0–3) of 1 or less;
- Prednisone or equivalent glucocorticoid use of less than or equal to 7.5 mg/day; and
- Tolerating standard immunosuppressant dosing.
The time to achieving LLDAS was compared between treatment groups using Cox regression. The cumulative time to LLDAS was compared using a Cochran–Mantel–Haenszel approach, and responses were compared using logistic regression. All P-values are nominal.