research HIGHLIGHTS

SYSTEMIC ERYTHEMATOSUS Other secondary end points met in TULIP-2 included reduc­ tions in the glucocorticoid dose and Positive results for anifrolumab in the severity of skin disease in patients treated with anifrolumab as compared with placebo. However, no in phase III SLE trial differences between the groups were seen in counts of swollen or tender The TULIP-2 trial of anifrolumab, improvement in all severe or joints or in the annualized rate of a against type I moderately severe organ system SLE flares. the phase III receptor (IFNAR), in manifestations — occurred quite Among the subpopulation of trials provide active systemic lupus erythematosus early after the initiation of treatment patients with a high baseline inter­ (SLE) has met its primary end point. and was sustained throughout the feron gene signature score (301 of encouraging “This is the first successful phase III 52-week study,” notes SLE researcher 362 patients; 83.1%), 48.0% of those evidence of trial in SLE since the Mary Crow, who was not involved treated with anifrolumab had a the efficacy program 10 years ago,” highlights in the study. BICLA response, compared with of anifrolumab study investigator Eric Morand. Type I interferon has long been 30.7% who received placebo; among The results revive hopes that the implicated in the pathogenesis of patients with a low interferon gene in SLE drug will be approved for use in SLE, SLE. “More than 20 years of basic signature, BICLA response occurred following the failure of the earlier science and translational research in 46.7% and 35.5%, respectively. TULIP-1 phase III study to meet its identifying the type I interferon Together, the phase III trials primary end point. pathway as prominently expressed provide encouraging evidence of the In TULIP-2, a BILAG-based in patients with SLE created a very efficacy of anifrolumab in SLE. Composite Lupus Assessment robust case for scientific testing of the “The role of anifrolumab in the (BICLA) response occurred in 86 of interferon hypothesis in SLE,” says treatment paradigm should ideally 180 patients (47.8%) who received Morand. By antagonizing IFNAR, the be tested in treatment strategy trials, anifrolumab at week 52, compared common interferon receptor subunit, which we hope will happen soon,” with 57 of 182 (31.5%) of those who anifrolumab prevents signalling by all says Morand. received placebo. “The improvement type I interferon subtypes. “In the case of any new drug for in BICLA — a measure that requires Although the TULIP-1 trial SLE, extensive real-world experience of anifrolumab failed to meet will be needed to gain a sense of the its primary end point, the SLE type of patients and clinical manifes- responder index (SRI)4 composite tations that are most responsive to measure, the drug showed efficacy the drug, as well as timing of admin- in some pre-specified secondary end istration and choice of concurrent points, including BICLA response. or sequential other agents,” Crow Following a careful analysis of comments, adding that targeting the TULIP-1 data (but before the of any one molecular pathway unblinding of TULIP-2 trial data), should not be expected to achieve the primary outcome measure for satisfactory clinical improvement in TULIP-2 was changed from SRI4 to many patients with SLE. “It is likely BICLA in a protocol amendment. that strategically targeting several “In contrast to BICLA, SRI4 reflects pathways will ultimately be required presence of disease activity related to achieve impressive clinical out- to a lupus manifestation rather than comes in patients with active SLE,” severity of a manifestation, so use she concludes. of BICLA allows for assessment of Sarah Onuora incremental response rather than requiring more complete resolution Original article Morand, E. F. et al. Trial of anifrolumab in active systemic lupus erythematosus. of a disease manifestation,” Crow N. Engl. J. Med. 382, 211–221 (2020) explains. Notably, SRI4 seemed to Related articles Murphy, G. & Isenberg, D. A. New therapies for systemic lupus erythematosus improve more with anifrolumab than — past imperfect, future tense. Nat. Rev. Rheumatol. with placebo in TULIP-2, although 15, 403–412 (2019) | Wampler Muskardin, T. & this outcome was not formally Niewold, T. B. Type I interferon in rheumatic diseases. Nat. Rev. Rheumatol. 14, 214–228 (2018)

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