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Systemic Lupus Erythematosus
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Vaneet K. Sandhu, Neha V. Chiruvolu, Daniel J. Wallace
The “interferon signature” is an established player in the pathophysiology of SLE, specifically IFN-1. Anifrolumab (ANI) is a fully human IgG1K monoclonal antibody to the type I interferon receptor subunit 1, thus blocking all signaling by any sort of type 1 interferon. Unfortunately, the first phase 3 trial (TULIP) did not demonstrate a significant effect on the primary end point, which was measured by SRI.67 A second phase 3 trial was conducted, this time using one of the secondary end points from the original trial as the primary end point: improvement in the British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA). This trial noted that a greater number of patients treated with ANI had a BICLA response than those treated with placebo. A significant reduction in glucocorticoid dosage and severity of skin manifestations in the ANI group was also noted, thereby showing promise in cutaneous lupus.68 Further investigation into impact of ANI on disease flares by using pooled data from the TULIP studies showed that patients who received ANI versus placebo had a lower annualized flare rate and overall fewer flares. Median time to first flare was also observed to be shorter.69 Anifrolumab is now FDA approved for treatment of moderate to severe SLE in adults alongside standard therapy.
Anti-IFNαR Mabs for the treatment of systemic lupus erythematosus
Published in Expert Opinion on Biological Therapy, 2021
Bethan Goulden, David Isenberg
TULIP-1 and −2 were large, multi-center, cross-continent trials, and the patient population studied clearly captured the target population for a novel add-on therapeutic agent – that is, predominantly females of childbearing age, albeit with a minority of patients of Black and Asian ethnicity, but with active disease despite standard of care therapy and a high burden of steroid use. The key finding in TULIP-2 that patients were able to wean steroids successfully whilst on anifrolumab is of benefit given their contribution to SLE related morbidity and mortality. While studies have largely looked at IV dosing, the prospect of an SC biologic for SLE would be a welcome addition to the SLE armamentarium. Anifrolumab has shown particularly promising results in those with cutaneous SLE, but further studies such as TULIP-LN should provide clarification about its effectiveness in lupus nephritis. Reviewing the data thus far, it is not clear that this is a treatment that should be restricted to those with a high IFNGS at baseline, though some of the data would support this idea. Further clinical and trial experience should help clarify its overall utility, if any, in a low IFNGS cohort. The fact that not all patients respond to anifrolumab is likely to be multifactorial, related to the pharmacodynamics of the biologic itself and heterogeneity in the immunopathology between patients and different organ systems, including the possible role of other IFN pathways such as that of the type III IFNs.
Systemic lupus erythematosus: an expert insight into emerging therapy agents in preclinical and early clinical development
Published in Expert Opinion on Investigational Drugs, 2020
Milena Tocut, Yehuda Shoenfeld, Gisele Zandman-Goddard
TULIP II used the same clinical trial design, looking at different endpoints. Anifrolumab showed to have better results on the BICLA disease activity index. Regarding reported adverse events, in this trial, serious adverse events such as pneumonia, SLE exacerbation, radius fracture and viral gastroenteritis were more common in the placebo group than in the anifolumab group. Upper respiratory and herpes-zoster infections were more common in the anifolumab group as opposed to the placebo group confirmed by similar results in the previous TULIP I trial. only one death was reported [47,48]. Another trial from 2020 (phase II trial) demonstrated that besides treatment efficacy in moderate to severe SLE, anifolumab at different IV doses (100 mg, 300 mg and 1000 mg) had a good beneficial and safety profile in Japanese patients after 48 and 156 weeks with similar rates of adverse events and serious adverse events. Therefore, in the near future anifrolumab will be available as an appropriate treatment [49].
Th1, Th2, and Th17 cytokines in systemic lupus erythematosus
Published in Autoimmunity, 2020
Farhana Muhammad Yusoff, Kah Keng Wong, Norhanani Mohd Redzwan
Anifrolumab, a type I IFN receptor monoclonal antibody antagonist, was used in a randomized, double-blind, placebo-controlled study for adult SLE patients with moderate-to-severe disease. SLE patients (n = 305) were randomized to receive intravenous anifrolumab with dosage of 300 and 1000 mg or placebo with addition to standard therapy. Higher number of patients who received anifrolumab met the primary endpoint compared with placebo (300 mg: 34.3%, n = 99; 1000 mg: 28.8%, n = 104; placebo: 17.6%, n = 102) [188]. However, in a subsequent randomized, double-blinded, 52-week placebo-controlled, multi-centre phase III trial (TULIP 1) involving 373 SLE patients, anifrolumab administration did not meet the primary endpoint of disease activity reduction measured by SRI4 at 12 months [189,190]. The summary of clinical trials for IFN-α and type I IFN receptor treatment in SLE patients are tabulated in Table 3.