ANIFROLUMAB EFFECTS ON RASH AND ARTHRITIS IN PATIENTS WITH SLE AND IMPACT OF INTERFERON SIGNAL IN POOLED DATA FROM PHASE 3 TRIALS
J. T. Merrill1, V. Werth2, R. Furie3, E. F. Morand4, J. M. Kahlenberg5, G. Abreu6, R. Tummala7
1Oklahoma Medical Research Foundation, Arthritis & Clinical Immunology Research Program, Oklahoma City, United States of America
2University of Pennsylvania and Corporal Michael J. Crescenz Veterans Administration Hospital, Dermatology, Philadelphia, United States of America
3Zucker School of Medicine at Hofstra/Northwell, Division of Rheumatology, Great Neck, United States of America
4Monash University, Centre for Inflammatory Disease Monash Health, Melbourne, United States of America
5University of Michigan, Division of Rheumatology, Ann Arbor, United States of America
6AstraZeneca, BioPharmaceuticals R&D, Gothenburg, Sweden
7AstraZeneca, BioPharmaceuticals R&D, Gaithersburg, United States of America
Background: Treatment with the type I interferon (IFN) receptor antibody anifrolumab was associated with clinical improvements in mucocutaneous and musculoskeletal disease activity in patients with systemic lupus erythematosus (SLE) in the phase 2 MUSE trial (NCT01438489) and phase 3 TULIP trials.
Because rash and arthritis are the most common manifestations of SLE, the effect of anifrolumab on these symptoms can be examined in biomarker-defined subsets, as previously reported for the MUSE trial.
Objectives: To evaluate the effect of anifrolumab on rash and arthritis in patients with SLE, and the impact of IFN gene signature (IFNGS) on treatment response, using disease measures of different stringency in pooled data from the phase 3 TULIP trials.
Methods: TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) were placebo-controlled, 52-week trials of intravenous anifrolumab administered every 4 weeks in patients with moderate to severe SLE.
In this post hoc analysis, outcomes of rash and arthritis were evaluated using mucocutaneous and musculoskeletal domains of the SLE Disease Activity Index 2000 (SLEDAI-2K) and the British Isles Lupus Assessment Group (BILAG) index. In addition, the modified Cutaneous Lupus Erythematosus Disease Area and Severity Index (mCLASI) score was used to evaluate rash, and tender and swollen joint counts were used to assess arthritis.
Results: 360 patients received anifrolumab 300 mg (IFNGS test–high, n=298; IFNGS test–low, n=62) and 366 patients were given placebo (IFNGS test–high, n=302; IFNGS test–low, n=64). Change from baseline to Week 52 compared with placebo was measured by outcomes, ordered by their stringency. More anifrolumab-treated patients achieved rash improvement using SLEDAI-2K (complete resolution: difference 13.5%, nominal
<0.001), BILAG (at least 1 severity grade lowering: difference 15.5%, nominal
<0.001), and mCLASI (≥50% improvement, if baseline score >0: difference 15.6%, nominal
<0.001). Results were comparable in the IFNGS test–high subset (SLEDAI-2K: difference 17.0%, nominal
<0.001, BILAG: difference 16.1%, nominal
<0.001; mCLASI: difference 18.1%, nominal
<0.001). There was a trend toward anifrolumab-associated rash improvement in IFNGS test–low patients using BILAG (
). More patients receiving anifrolumab had SLEDAI-2K–defined resolution in arthritis (difference 8.2%, nominal
=0.029), BILAG severity lessening (difference 11.8%, nominal
=0.002), and ≥50% decrease in tender/swollen joint counts, when ≥6 at baseline (difference 12.6%, nominal
=0.016). Results were comparable in the IFNGS test–high subset (SLEDAI-2K: difference 11.7%, nominal
=0.005; BILAG: difference 12.9%, nominal
=0.003; joint counts: difference 11.3%, nominal
=0.054). In IFNGS test–low patients, there was a trend toward anifrolumab-associated arthritis improvement when measured using BILAG, and the effect of anifrolumab on the number of swollen/tender joint counts was similar to the IFNGS test–high group, although the IFNGS test–low sample size in this analysis was very small (
Conclusion: In pooled data from the TULIP trials, anifrolumab treatment was associated with improvements in rash and arthritis using measures of different stringency. The SLEDAI-2K findings were largely driven by the subset of patients who were IFNGS test–high. However, using measures that were more sensitive to change, despite small sample sizes, IFNGS test–low patients may also have benefit.
Furie R, et al.
Merrill JT, et al.
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Furie RA, et al.
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Acknowledgements: Writing assistance by Victoria Alikhan, PhD, of JK Associates Inc., part of Fishawack Health. This study was sponsored by AstraZeneca.
Disclosure of Interests: Joan T Merrill Consultant of: AstraZeneca, AbbVie, Amgen, Aurinia, BMS, EMD Serono, GSK, Remegen, Janssen, Provention, and UCB, Grant/research support from: BMS and GSK, Victoria Werth Speakers bureau: University of Pennsylvania, who own the copyright for the CLASI and SDASI, Consultant of: AbbVie, Amgen, Argenx, AstraZeneca, Biogen, BMS, Celgene, Chrysalis, CSL Behring, Cugene, Eli Lilly, EMD Serono, Genentech, GSK, Incyte, Idera, Janssen, Kirin, Medimmune, Medscape, Nektar, Octapharma, Pfizer, Principa, Regeneron, Resolve, and Viela Bio, Grant/research support from: AstraZeneca, Biogen, Celgene, Corbus Pharmaceuticals, Genentech, Gilead, Janssen, Pfizer, Syntimmune, and Viela Bio, Richard Furie Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, Eric F. Morand Speakers bureau: AstraZeneca, Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, J Michelle Kahlenberg Consultant of: Admirex Pharmaceuticals, AstraZeneca, Aurinia Pharmaceuticals, BMS, Boehringer Ingelheim, Eli Lilly, and Ventus Therapeutics, Grant/research support from: BMS/Celgene and Q32 Bio, Gabriel Abreu Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca
Citation: Ann Rheum Dis, volume 80, supplement 1, year 2021, page 75
Session: SLE, Sjögren’s and APS - treatment and SLE, Sjögren’s and APS - clinical aspects (other than treatment)