Efficacy and Safety of Ustekinumab in Patients with Active Systemic Lupus Erythematosus: Results Through 2 Years of an Open-Label Extension in a Phase 2 Study

Objective To evaluate long-term efficacy and safety of ustekinumab through 2 years in patients with active systemic lupus erythematosus (SLE). Methods This was a placebo-controlled (Week24) phase 2 study in 102 patients with seropositive active SLE. Patients were randomized to ustekinumab (~6 mg/kg single IV infusion, then 90 mg SC every 8 weeks) or placebo, added to background therapy. Placebo patients initiated ustekinumab (90mg SC Q8W) at Week24. Patients could enter an optional open-label study extension after Week40 (final ustekinumab administration at Week104). Efficacy assessments included SRI-4, SLEDAI-2K, PGA, and CLASI. Observed data are reported for the extension period. The final efficacy assessment was at Week112; safety was monitored through Week120. Results In this subset of patients who entered the study extension, 24 in the ustekinumab group and 14 in the placebo-crossover group completed study treatment. At Week112, 79% and 92%, respectively, had an SRI-4 response, 92% in both groups had ≥4-point improvement from baseline in SLEDAI-2K score, 79% and 93%, respectively, had ≥30% improvement from baseline in PGA, 86% and 91%, respectively, had ≥50% improvement in active joint (pain and inflammation) count, and 79% and 100%, respectively, had ≥50% improvement in CLASI activity score. No deaths, malignancies, opportunistic infections, or tuberculosis cases occurred. Safety events were consistent with the known ustekinumab safety profile. Conclusion In the 46 patients who entered the voluntary extension of this phase 2 study, clinical benefit in global and organ-specific SLE-activity measures was observed with ustekinumab through 2years with no new or unexpected safety findings. clinicaltrials.gov: NCT02349061

POS0701 ANIFROLUMAB, AN ANTI-INTERFERON-Α RECEPTOR MONOCLONAL ANTIBODY IN SYSTEMIC LUPUS ERYTHEMATOSUS- A META ANALYSIS

Background:Type I interferons such as Anifrolumab have been implicated in Systemic lupus erythematosus (SLE) pathogenesis on the basis of increased interferon-stimulated gene expression and genetic susceptibility. Little is known regarding its efficacy and safety profile.Objectives:To assess the efficacy and safety of Anifrolumab in patients with SLE.Methods:Electronic databases (PubMed, Embase, Scopus, Cochrane) were searched from inception until December 15th, 2020. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p<0.05. The primary outcome of interest was British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA). Secondary outcomes included the proportion of patients who achieved an SLE responder index of 4 (SRI-4) reduction of 50% or more in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), reductions in the glucocorticoid dose and adverse effects.Results:A total of three studies1,2,3 with 839 participants (Anifrolumab=372, Placebo=467) were included in our analysis. Follow-up duration was at week 52. A statistically significant different was observed in the Anifrolumab arm in terms of BICLA response (OR 0.44 95%CI 0.34-0.59;p < 0.00001, I2=4), ≥50% reduction in CLASI activity score (OR 0.36 95%CI 0.21-0.60;p=0.0001, I2=0), glucocorticoid reduction (OR 0.41 95%CI 0.28-0.59;p<0.00001; I2=0) and SRI-4 response (OR 0.52 95% CI 0.30-0.90; p=0.02, I2=75). However, Adverse events were less likely in the placebo arm as compared to Anifrolumab (OR 1.54 95%CI 1.05-2.25; p=0.03; I2=0).Conclusion:Anifrolumab was found to be more effective than placebo for the management of SLE, but may also cause more severe adverse effects.References:[1]Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, Richez C, Bae SC, Brohawn PZ, Pineda L, Berglind A, Tummala R; TULIP-2 Trial Investigators. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020 Jan 16;382(3):211-221. doi: 10.1056/NEJMoa1912196. Epub 2019 Dec 18. PMID: 31851795.[2]Furie R, Khamashta M, Merrill JT, Werth VP, Kalunian K, Brohawn P, Illei GG, Drappa J, Wang L, Yoo S; CD1013 Study Investigators. Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017 Feb;69(2):376-386. doi: 10.1002/art.39962. PMID: 28130918; PMCID: PMC5299497.[3]Furie RA, Morand EF, Bruce IN, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol 2019; 1(4):e208-e219.Disclosure of Interests:None declared

A Prospective Study of Cytomegalovirus-Specific Cell-mediated Immune Monitoring and Cytomegalovirus Infection in Patients with Active Systemic Lupus Erythematosus Receiving Immunosuppressants

Introduction The effects of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) on CMV infection in patients with autoimmune diseases receiving immunosuppressants have not been explored. Methods Patients with active systemic lupus erythematosus (SLE) were preemptively monitored for clinically significant CMV infection (CsCMVI, defined as plasma CMV DNA loads &gt; 3 log10 IU/mL). CMV-specific CMI was assessed using an enzyme-linked immunosorbent assay (QuantiFERON-CMV®, QF) before as well as 1 and 3 months after intense immunosuppressive therapy. Results The study included 55 patients with active SLE; patients had a mean age of 34 years (standard deviation [SD] 13 years), a median SLEDAI-2K score of 14 (SD 8), and 93% were female. Most patients had renal involvement (67%), received methylprednisolone (93%), and were CMV seropositive (95%). Thirteen (23.6%) patients developed CsCMVI. Among patients with active SLE who were QF-negative (QF–) and QF-positive (QF+) before receiving immunosuppressive therapy, 28.6% and 25% developed CsCMVI, respectively (p=0.69). However, 1 month post-immunosuppression, more QF– than QF+ patients developed CsCMVI (44.4% vs. 11.8%, p=0.03; adjusted hazard ratio 4.97 [95% confidence interval 1.07–23.10], p=0.04). Conclusions Patients with active SLE and low CMV-specific T cell responses could develop CMV infection after receiving immunosuppressants. Further studies should focus on CMV-specific CMI among patients with autoimmune diseases.