SRI-4 Response Research Articles

The safety and efficacy of Baricitinib for systemic lupus erythematosus: a systematic review and meta-analysis of randomized controlled trials.

Baricitinib is a JAK1 and JAK2 inhibitor approved for treating active rheumatoid arthritis and atopic dermatitis. Therefore, the authors aim to evaluate the safety and efficacy of once-daily oral Baricitinib 2mg or 4mg versus placebo in active SLE patients receiving standard care. The authors synthesized randomized controlled studies (RCTs) from MEDLINE, Scopus, EMBASE, PubMed, and Cochrane Library until 20 March 2023. The study protocol was registered in PROSPERO. Three RCTs with 1849 participants were included. The Baricitinib group had a significant SRI-4 response [RR: 1.11 with 95% CI (1.03, 1.21), P=0.008] and greater than or equal to 4-point SLEDAI-2K domain improvement [RR: 1.13 with 95% CI (1.02, 1.25), P=0.02] compared to the placebo group; however, there was no statistically significant difference between the two groups, regarding the secondary endpoints. For safety outcomes, Baricitinib was significantly associated with a higher incidence of Any serious adverse event [RR: 1.48 with 95% CI (1.07, 2.05), P=0.02]. Baricitinib is associated with significant outcomes of SRI-4 response, greater than or equal to 4-point improvement SLEDAI-2K score, and Joint Indices. Regarding safety, there was no difference in the outcomes other than the serious adverse events.

Efficacy and Safety of Upadacitinib or Elsubrutinib Alone or in Combination for Patients With Systemic Lupus Erythematosus: A Phase 2 Randomized Controlled Trial.

The 48-week, phase 2 SLEek study (NCT03978520) evaluated the efficacy and safety of upadacitinib (JAK inhibitor) and elsubrutinib (BTK inhibitor) alone or in combination (ABBV-599) in adults with moderately to severely active systemic lupus erythematosus (SLE). Patients were randomized 1:1:1:1:1 to elsubrutinib 60 mg and upadacitinib 30 mg once daily (ABBV-599 high dose), elsubrutinib 60 mg and upadacitinib 15 mg once daily (ABBV-599 low dose), elsubrutinib 60 mg once daily (QD), upadacitinib 30 mg QD, or placebo QD. The primary endpoint was the proportion of patients achieving both Systemic Lupus Erythematosus Responder Index 4 (SRI-4) and glucocorticoid dose ≤10 mg QD at week 24. Additional assessments through week 48 included British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA) and Lupus Low Disease Activity State (LLDAS) responses, number of flares, time to first flare, and adverse events. The study enrolled 341 patients. The ABBV-599 low dose and elsubrutinib arms were discontinued after a planned interim analysis showed lack of efficacy (no safety concerns). More patients achieved the primary endpoint with upadacitinib (54.8%; P = 0.028) and ABBV-599 high dose (48.5%; P = 0.081) versus placebo (37.3%). SRI-4, BICLA, and LLDAS response rates were higher for both upadacitinib and ABBV-599 high dose versus placebo at weeks 24 and 48. Flares were reduced, and time to first flare through week 48 was substantially delayed with both upadacitinib and ABBV-599 high dose versus placebo. No new safety signals were observed beyond those previously reported for upadacitinib or elsubrutinib. Upadacitinib 30 mg alone or in combination with elsubrutinib (ABBV-599 high dose) demonstrated significant improvements in SLE disease activity and reduced flares and were well tolerated through 48 weeks.

Efficacy and safety study of targeted small-molecule drugs in the treatment of systemic lupus erythematosus

BackgroundTargeted small-molecule drugs in the treatment of systemic lupus erythematosus (SLE) have attracted increasing attention from clinical investigators. However, there is still a lack of evidence on the difference in the efficacy and safety of different targeted small-molecule drugs. Therefore, this study was conducted to assess the efficacy and safety of different targeted small-molecule drugs for SLE.MethodsRandomized controlled trials (RCTs) on targeted small-molecule drugs in the treatment of SLE in PubMed, Web of Science, Embase, and Cochrane Library were systematically searched as of April 25, 2023. Risk of bias assessment was performed for included studies using the Cochrane’s tool for evaluating the risk of bias. The primary outcome indicators were SRI-4 response, BICLA response, and adverse reaction. Because different doses and courses of treatment were used in the included studies, Bayesian network meta-regression was used to investigate the effect of different doses and courses of treatment on efficacy and safety.ResultsA total of 13 studies were included, involving 3,622 patients and 9 targeted small-molecule drugs. The results of network meta-analysis showed that, in terms of improving SRI-4, Deucravacitinib was significantly superior to that of Baricitinib (RR = 1.32, 95% CI (1.04, 1.68), P < 0.05). Deucravacitinib significantly outperformed the placebo in improving BICLA response (RR = 1.55, 95% CI (1.20, 2.02), P < 0.05). In terms of adverse reactions, targeted small-molecule drugs did not significantly increase the risk of adverse events as compared to placebo (P > 0.05).ConclusionBased on the evidence obtained in this study, the differences in the efficacy of targeted small-molecule drugs were statistically significant as compared to placebo, but the difference in the safety was not statistically significant. The dose and the course of treatment had little impact on the effect of targeted small-molecule drugs. Deucravacitinib could significantly improve BICLA response and SRI-4 response without significantly increasing the risk of AEs. Therefore, Deucravacitinib is very likely to be the best intervention measure. Due to the small number of included studies, more high-quality clinical evidence is needed to further verify the efficacy and safety of targeted small-molecule drugs for SLE.

Effect of belimumab in patients with systemic lupus erythematosus treated with low dose or no corticosteroids.

Systemic lupus erythematosus (SLE) responder index (SRI)-4 response has been achieved with belimumab treatment in patients with moderate disease activity in cornerstone clinical trials and following studies. However, most studies involved patients treated with a mean prednisolone-equivalent dose of approximately 10 mg/d and focused on the steroid-sparing effect of belimumab. We aimed to identify the effect of belimumab in patients with mild-to-moderate SLE who were treated with low-dose or no corticosteroids. We retrospectively reviewed the electronic medical records of patients treated with belimumab for at least 6 months between May 2021 and June 2022. The primary endpoint was SRI-4 response at 6 months. Thirty-one patients were included (13 low dose- and 18 steroid non-users). The mean age was 39.2 ± 11.4 years, and 90.3% of patients were female. The baseline Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score was 6.0 (4.0-9.0). The primary endpoint was achieved in 32.3% (10/31) of patients. Significant improvements in anemia, C4 levels, and SELENA-SLEDAI score were observed during treatment. Univariate analysis showed that the baseline SELENA-SLEDAI and arthritis were significantly associated with SRI-4 response at 6 months, and only the SELENA-SLEDAI remained significant (p = 0.014) in multivariate analysis. This cohort study is the first to report the efficacy of belimumab after minimizing the effect of corticosteroids. Belimumab showed efficacy in improving the SELENA-SLEDAI score, anemia, and low C4 in patients who did not receive corticosteroids or received only low doses.

Efficacy and safety of baricitinib in treatment of systemic lupus erythematosus: a systematic review and meta-analysis

BackgroundSLE is an autoimmune disease marked by broad immunological dysregulation and multi-system inflammation. Baricitinib is one of the novel treatments for SLE. We conducted this meta-analysis to evaluate its safety and effectiveness in treating SLE.MethodWe looked for all published randomized controlled trials in PubMed, Scopus, Web of Science, and Cochrane and included all RCTs comparing baricitinib and placebo in the treatment of SLE. Review Manager 5.4 program was used for data analysis.ResultsThree trials with a total of 1849 individuals were included. Participants in the baricitinib group were significantly more likely to attain SRI-4 response than those in the placebo group [RR = 1.11, 95% CI (1.02, 1.21), P = 0.01]. Additionally, baricitinib performed better than the placebo in terms of reduction of ≥ 4 points from baseline in SLEDAI-2 K score [RR = 1.13, 95% CI (1.04, 1.22), P = 0.004]. In terms of SLEDAI-2 K remission of arthritis or rash, baricitinib was also superior to placebo [RR = 1.08, 95% CI (1.00, 1.17), P = 0.04]. Treatment-emergent adverse events did not differ significantly [RR = 1.01, 95% CI (0.97, 1.05), P = 0.61].ConclusionBaricitinib is potentially safe and effective in the treatment of SLE. It has successfully met the study’s primary endpoint and some secondary endpoints highlighting its potential to improve the outcomes of SLE. Despite achieving an SRI-4 response, glucocorticoids sparing and some other secondary outcomes weren’t reached by baricitinib.

Treatment of active systemic lupus erythematosus with baricitinib: A meta-analysis of randomized controlled trials.

This study aimed to evaluate the safety and effectiveness of baricitinib in patients with systemic lupus erythematosus (SLE). We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register to find relevant publications. Using data from randomized controlled trials (RCTs), we performed a meta-analysis to investigate the safety and efficacy of baricitinib in patients with active SLE who did not respond well to standard treatments. A total of 1849 individuals (1235 experimental participants and 614 controls) from three RCTs on baricitinib were included. A reduction of ≥ 4 points from baseline in SLEDAI-2K score in the baricitinib 4mg group was greater than the placebo group's reduction (odds ratio [OR] = 1.407, 95% confidence interval [CI] 1.123-1.763, p = .003). The baricitinib 4mg group significantly outperformed the placebo group in terms of SLEDAI-2K remission of arthritis or rash (OR = 1.327, 95% CI = 1.059-1.663, p = .014). Other effectiveness outcomes such as the SRI4 response did not substantially improve in the baricitinib 4mg group when compared with the placebo group. And there were no significant increase in the efficacy outcomes in the baricitinib 2mg group than in the placebo group. However, there was a substantially higher incidence of severe adverse events (SAE) and serious infections in the baricitinib 4mg group (OR = 1.493, 95% CI = 1.002-2.225, p = .049; OR = 2.303, 95% CI = 1.147-4.622, p = .019) compared to the placebo group. There were no differences between the baricitinib 2mg and placebo groups in any of the safety outcome data. Meta-analysis reveals that baricitinib 4mg is beneficial for treating active SLE in terms of a reduction of ≥ 4 points from baseline in SLEDAI-2K score and SLEDAI-2K remission of arthritis or rash. However, the higher frequency of SAEs and serious infections was observed in the group receiving baricitinib 4mg.

Belimumab versus anifrolumab in adults with systemic lupus erythematosus: an indirect comparison of clinical response at 52 weeks

ObjectiveTo generate comparative efficacy evidence of belimumab versus anifrolumab in SLE that can inform treatment practices.MethodsThe SLE Responder Index (SRI)-4 response at 52 weeks of belimumab versus anifrolumab was evaluated...

Efficacy and Safety of the Bruton's Tyrosine Kinase Inhibitor Evobrutinib in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Trial.

Evobrutinib is a highly selective, orally administered Bruton's tyrosine kinase (BTK) inhibitor. The objective of this phase II, multicenter, randomized, double-blind, placebo-controlled trial was to evaluate the efficacy and safety of evobrutinib in patients with active autoantibody-positive systemic lupus erythematosus (SLE). Patients were diagnosed with SLE by either the Systemic Lupus International Collaborating Clinics criteria or at least four American College of Rheumatology criteria 6 months or more prior to screening, had an SLE Disease Activity Index-2000 score of 6 or more, were autoantibody-positive and on standard-of-care therapy. Randomization was 1:1:1:1 to oral evobrutinib 25 mg once daily (QD), 75 mg QD, 50 mg twice daily, or placebo. Primary efficacy endpoints were SLE responder index (SRI)-4 response at week 52 and SRI-6 response at week 52 in the high disease activity subpopulation. Safety endpoints included treatment-emergent adverse events (TEAEs). A total of 469 patients were randomized and received at least one dose of evobrutinib or placebo at the time of primary analysis. Mean (SD) age at baseline was 40.7 (±12.3) years; 94.9% of patients were female. Neither primary efficacy endpoint was met. All doses of evobrutinib were well tolerated, and there was no clear dose effect on the incidence of reported TEAEs, or serious TEAEs, including severe infections. This phase II, dose-ranging trial in SLE failed to show a treatment effect of evobrutinib versus placebo at any dose. Evobrutinib was generally well tolerated, with no dose effect observed for TEAEs. These results suggest that BTK inhibition does not appear to be an effective therapeutic intervention for patients with SLE.

Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus

ObjectiveEvaluate the efficacy and safety of ustekinumab, an anti-interleukin-12/23 p40 antibody, in a phase 3, randomised, placebo-controlled study of patients with active systemic lupus erythematosus (SLE) despite receiving standard-of-care.MethodsActive SLE...

Early Changes in B and Plasma Cell Subsets and Traditional Serological Markers as Predictors of SRI-4 Response to Therapy in Systemic Lupus Erythematosus

ObjectiveWith the premise of the hypothesis that early biological responses to therapy for active systemic lupus erythematosus (SLE) portend later clinical improvements, we studied changes in B cell subsets and traditional serological markers in relation to clinical response to standard therapy (ST) with or without the addition of belimumab.Patients and MethodsWe analyzed data from the BLISS-76, BLISS-SC, and BLISS Northeast Asia trials (N = 1712). Circulating CD19+ B cell subsets were determined by flow-cytometry. We studied associations of relative to baseline percentage changes in circulating B and plasma cell subsets, anti-dsDNA antibody levels and complement levels with SLE Responder Index (SRI)-4 response after 52 weeks of treatment. Changes occurring through week 8 were deemed “rapid,” through week 24 “early,” and thereafter “delayed”.ResultsIn the analysis of the entire cohort, SRI-4 responders showed more prominent decreases from baseline through week 52 in CD19+CD20+CD27– naïve B cells (median change: −61.2% versus −50.0%; P = 0.004), CD19+CD20–CD27bright plasmablasts (−44.9% versus −33.3%; P = 0.011), and CD19+CD20–CD138+ long-lived plasma cells (−48.2% versus −37.1%; P = 0.024), and a more prominent rapid (+92.0% versus +66.7%; P = 0.002) and early (+60.0% versus +49.5%; P = 0.033) expansion of CD19+CD20+CD27+ memory B cells than non-responders. More prominent rapid reductions in anti-dsDNA (−14.8% versus −8.7%; P = 0.043) and increases in C3 (+4.9% versus +2.1%; P = 0.014) and C4 levels (+11.5% versus +8.3%; P = 0.017) were documented in SRI-4 responders compared with non-responders among patients who received add-on belimumab, but not among patients who received non-biological ST alone.ConclusionSRI-4 responders showed a more prominent rapid expansion of memory B cells and more prominent delayed reductions in naïve B cells, plasmablasts and long-lived plasma cells. Moreover, clinical response to belimumab was associated with preceding more prominent reductions of anti-dsDNA and increases in C3 and C4 levels. Monitoring biological changes may prove useful in SLE patient surveillance and early treatment evaluation.

Phase 2 Trial of Iberdomide in Systemic Lupus Erythematosus

BackgroundIberdomide, a cereblon modulator promoting degradation of the transcription factors Ikaros and Aiolos, which affect leukocyte development and autoimmunity, is being evaluated for the treatment of systemic lupus erythematosus (SLE).MethodsIn this phase 2 trial, we randomly assigned patients in a 2:2:1:2 ratio to receive oral iberdomide (at a dose of 0.45, 0.30, or 0.15 mg) or placebo once daily for 24 weeks, in addition to standard medications. The primary end point at week 24 was a response on the SLE Responder Index (SRI-4), which was defined as a reduction of at least 4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 score (a 24-item weighted score of lupus activity that ranges from 0 to 105, with higher scores indicating greater disease activity), no new disease activity as measured on the British Isles Lupus Assessment Group 2004 index, and no increase of 0.3 points or more in the Physician’s Global Assessment score (on a visual-analogue scale ranging from 0 [no disease activity] to 3 [maximal disease]).ResultsA total of 288 patients received the assigned intervention: 81 received iberdomide at a dose of 0.45 mg, 82 received iberdomide at a dose of 0.30 mg, 42 received iberdomide at a dose of 0.15 mg, and 83 received placebo. At week 24, the percentages of patients with an SRI-4 response were 54% in the iberdomide 0.45-mg group, 40% in the iberdomide 0.30-mg group, 48% in the iberdomide 0.15-mg group, and 35% in the placebo group (adjusted difference between the iberdomide 0.45-mg group and the placebo group, 19.4 percentage points; 95% confidence interval, 4.1 to 33.4; P=0.01), with no significant differences between the groups that received the lower doses of iberdomide and the group that received placebo. Iberdomide-associated adverse events included urinary tract and upper respiratory tract infections and neutropenia.ConclusionsIn this 24-week, phase 2 trial involving patients with SLE, iberdomide at a dose of 0.45 mg resulted in a higher percentage of patients with an SRI-4 response than did placebo. Data from larger, longer trials are needed to determine the efficacy and safety of iberdomide in SLE. (Funded by Bristol Myers Squibb; ClinicalTrials.gov number, NCT03161483; EudraCT number, 2016-004574-17.)

Reductions in circulating B cell subsets and immunoglobulin G levels with long-term belimumab treatment in patients with SLE

ObjectiveTo examine the long-term changes in circulating B cell subsets and IgG levels at 5+ years of continuous belimumab treatment and their correlations with efficacy and safety measures.MethodsThis was a...

Efficacy and safety of belimumab in paediatric and adult patients with systemic lupus erythematosus: an across-study comparison

ObjectiveTo assess the efficacy and safety of belimumab in paediatric versus adult patients with systemic lupus erythematosus (SLE).MethodsWe performed across-study comparisons of patients with active SLE who received belimumab or...

POS0698 BIIB059 DEMONSTRATED A CONSISTENT THERAPEUTIC EFFECT ON SRI-4 RESPONSE ACROSS SUBGROUPS OF PARTICIPANTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN THE LILAC PHASE 2 STUDY

Background:Type I interferons and other inflammatory mediators derived from plasmacytoid dendritic cells (pDCs) are implicated in systemic lupus erythematous (SLE) pathology. BIIB059 is a humanized monoclonal antibody that targets blood dendritic cell antigen 2 (BDCA2), a pDC-specific receptor. The binding of BIIB059 to BDCA2 leads to rapid internalization of BDCA2 from the surface of pDCs and subsequent inhibition of interferon, cytokine, and chemokine production. In Part A of the 2-part, phase 2 LILAC study (NCT02847598), BIIB059 significantly reduced SLE activity, as evidenced by reduced total active joint count (primary endpoint) and higher SLE Responder Index (SRI-4)1 response (a secondary endpoint) versus placebo.2Objectives:To evaluate SRI-4 response for BIIB059 versus placebo at Week 24 in SLE participant subgroups.Methods:Enrollment in LILAC Part A was open to adults fulfilling ≥ 4 of 11 revised 1997 ACR criteria for classification of SLE, with ≥ 4 tender and ≥ 4 swollen joints, active skin disease, and positive lupus antibodies. Participants were randomized to receive either BIIB059 450 mg or placebo subcutaneously every 4 weeks for 20 weeks (with an additional dose at Week 2). SRI-4 response at Week 24 was analyzed in subgroups, though analyses were limited by small sample sizes and were not powered for statistical testing.Results:In LILAC Part A, 64 and 56 participants were dosed with BIIB059 450 mg and placebo, respectively. At week 24, SRI-4 response rate was observed in favor of BIIB059 regardless of the baseline disease activity, such as SLEDAI-2K &lt;10 versus ≥10, presence of BILAG-2004 grade A or B arthritis, oral corticosteroid usage, positivity for anti-ds DNA autoantibody and/or complement status, with point estimates for least-squares mean differences as well as corresponding 95% CIs consistently favoring BIIB059 (Figure 1). The incidence of adverse events in the overall study population was similar between the placebo and BIIB059 groups.2Conclusion:BIIB059 treatment was associated with greater SRI-4 response rate, consistent among different subgroups of baseline disease activity as measured by SLEDAI-2K and BILAG-2004, glucocorticoid dosage, and serology. These findings provide additional evidence of the potential benefit of BIIB059 for the treatment of patients with active SLE.

Repository Corticotropin Injection for Persistently Active Systemic Lupus Erythematosus: Results from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

IntroductionWe assessed the efficacy and safety of repository corticotropin injection (RCI; Acthar® Gel) for persistently active systemic lupus erythematosus (SLE) despite use of moderate-dose glucocorticoids.MethodsThis multicenter, double-blind, randomized, placebo-controlled study enrolled patients ≥ 18 years with active SLE and moderate to severe rash and/or arthritis despite stable glucocorticoid doses (7.5–30 mg/day prednisone equivalent) and antimalarials for ≥ 4 weeks and/or immunosuppressants for ≥ 8 weeks before screening. Stable glucocorticoid doses were required through week 16 with optional taper from weeks 16 to 24. Patients were randomized (1:1) to 80 U RCI subcutaneously or placebo every other day to week 4, then twice weekly to week 24. Endpoints included the proportion of SLE Responder Index (SRI)-4 responders at week 16; changes from baseline to week 16 in 28 Swollen Joint Count/Tender Joint Count (28 SJC/TJC) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-Activity score; and changes from baseline to week 24 in inflammatory cytokines. Safety was assessed by adverse events.ResultsIn the modified intention-to-treat population (RCI, n = 84; placebo, n = 85), the proportion of SRI-4 responders at week 16 was not significantly different between groups (RCI, 47.6%; placebo, 43.5%; OR [95% CI] 1.2 [0.6 to 2.2]; p = 0.5762). RCI treatment resulted in a reduction from baseline to week 16 in 28 SJC/TJC and CLASI-Activity score and from baseline to week 8 in B-cell activating factor cytokine. Post hoc analyses demonstrated a greater proportion of BILAG-based Combined Lupus Assessment responders for RCI than placebo at weeks 4, 12, and 20 and greater SRI-4 response in RCI-treated patients with baseline SLE Disease Activity Index-2000 ≥ 10 and CLASI-Activity ≥ 11. No new safety signals were identified.ConclusionsDespite failure to achieve the primary endpoint, these results support the utility of RCI for treating persistently active SLE.Trial RegistrationClinicalTrials.gov identifier NCT02953821.Electronic Supplementary MaterialThe online version of this article (10.1007/s40744-020-00236-1) contains supplementary material, which is available to authorized users.

Interferon blockade in systemic lupus erythematosus: Light at the end of the tunnel for novel therapies for lupus?

Interferon blockade in systemic lupus erythematosus: Light at the end of the tunnel for novel therapies for lupus?

Pharmacogenetic analysis of belimumab fails to identify robust genetic predictors of efficacy in lupus.

GlaxoSmithKline (GSK) conducted pharmacogenetic (PGx) analyses to determine whether genetic variants influence response to belimumab treatment in patients with systemic lupus erythematosus (SLE). We conducted an exploratory genome-wide meta-analysis (GWAS) of 10.9 million genetic variants and the efficacy data from 816 belimumab-treated SLE patients in three phase 3 belimumab clinical studies. Two highly correlated variants, rs293983 and rs364370, in the ANO3 (anoctamin 3) gene region were significantly associated with efficacy as measured by the SLE Response Index (SRI4) with a per-T-allele odds ratio (OR) of 2.15 [95% confidence interval (CI): 1.66-2.79, P=8.0×10]. In contrast, there was no association with SRI4 response in 577 placebo-treated patients (per-T-allele OR: 0.98; 95% CI: 0.74-1.29, P=0.87). A post-hoc analysis by geographic region revealed a strong SRI4 response signal in 157 belimumab-treated patients from Asia (per-T-allele OR=2.85, 95% CI: 1.41-5.74, P=0.0021). On the basis of this encouraging finding in Asian patients, we conducted a confirmatory analysis of the SRI4 end point in an independent phase 3 study of SLE patients from northeast Asia. We found no evidence of an association between rs293983 and SRI4 response in 204 belimumab-treated patients (per-T-allele OR: 0.90, 95% CI: 0.52-1.57, P=0.64). The inability to replicate the observed GWAS effect suggests this was a false positive result; hence, we failed to identify any genetic variants significantly associated with belimumab efficacy.

A pivotal phase III, randomised, placebo-controlled study of belimumab in patients with systemic lupus erythematosus located in China, Japan and South Korea

BackgroundIntravenous belimumab plus standard of care (SoC) is approved in the USA and Europe for treatment of active, autoantibody-positive systemic lupus erythematosus (SLE).MethodsThis phase III, multicentre, randomised, double-blind, placebo-controlled study...

Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty‐Two–Week Randomized, Double‐Blind, Placebo‐Controlled Study

ObjectiveTo assess the efficacy and safety of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE).MethodsPatients with moderate‐to‐severe SLE (score of ≥8 on the Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] version of the SLE Disease Activity Index [SLEDAI]) were randomized 2:1 to receive weekly SC belimumab 200 mg or placebo by prefilled syringe in addition to standard SLE therapy for 52 weeks. The primary end point was the SLE Responder Index (SRI4) at week 52. Secondary end points were reduction in the corticosteroid dosage and time to severe flare. Safety was assessed according to the adverse events (AEs) reported and the laboratory test results.ResultsOf 839 patients randomized, 836 (556 in the belimumab group and 280 in the placebo group) received treatment. A total of 159 patients withdrew before the end of the study. At entry, mean SELENA–SLEDAI scores were 10.5 in the belimumab group and 10.3 in the placebo group. More patients who received belimumab were SRI4 responders than those who received placebo (61.4% versus 48.4%; odds ratio [OR] 1.68 [95% confidence interval (95% CI) 1.25–2.25]; P = 0.0006). In the belimumab group, both time to and risk of severe flare were improved (median 171.0 days versus 118.0 days; hazard ratio 0.51 [95% CI 0.35–0.74]; P = 0.0004), and more patients were able to reduce their corticosteroid dosage by ≥25% (to ≤7.5 mg/day) during weeks 40–52 (18.2% versus 11.9%; OR 1.65 [95% CI 0.95–2.84]; P = 0.0732), compared with placebo. AE incidence was comparable between treatment groups; serious AEs were reported by 10.8% of patients taking belimumab and 15.7% of those taking placebo. A worsening of IgG hypoglobulinemia by ≥2 grades occurred in 0.9% of patients taking belimumab and 1.4% of those taking placebo.ConclusionIn patients with moderate‐to‐severe SLE, weekly SC doses of belimumab 200 mg plus standard SLE therapy significantly improved their SRI4 response, decreased severe disease flares as compared with placebo, and had a safety profile similar to placebo plus standard SLE therapy.

Efficacy and safety of an interleukin 6 monoclonal antibody for the treatment of systemic lupus erythematosus: a phase II dose-ranging randomised controlled trial

ObjectivesThis phase II trial evaluated the efficacy and safety of an interleukin (IL) 6 monoclonal antibody for systemic lupus erythematosus (SLE).MethodsPatients with active disease were randomised to placebo or PF-04236921...