Systemic Lupus Erythematosus Responder Index Research Articles

Molecular basis for the disease-modifying effects of belimumab in systemic lupus erythematosus and molecular predictors of early response: blood transcriptome analysis implicates the innate immunity and DNA damage response pathways

ObjectivesBelimumab is a putative disease-modifying agent in systemic lupus erythematosus (SLE), yet the molecular underpinnings of its effects and the ability to predict early clinical response remain unexplored. To address...

Predictive biomarkers for low-dose IL-2 therapy efficacy in systemic lupus erythematosus: a clinical analysis

BackgroundLow-dose IL-2 (Ld-IL2) has shown favorable therapeutic effects in systemic lupus erythematosus (SLE) therapy. However, previous clinical trials reported an SLE Responder Index-4 (SRI-4) response rate of 65.52%-68%, with approximately half failing to achieve the primary endpoint by week 24. Our study aims to determine the real-world use of Ld-IL2 and to identify determinants of its effectiveness in SLE.MethodsWe pooled data from 342 SLE patients undergoing sequential Ld-IL2 treatment, with 314 persisting for over 3 months were included in effectiveness and prediction analyses. All patients were categorized into responder (n = 136) and non-responder group (n = 178) according to SRI-4. Lupus Low Disease Activity State (LLDAS) was also analyzed to validate our results.ResultsRash, lower complement 3 (C3), and renal involvement including urine protein, urine occult blood and urine casts emerged as prominent predictors of achieving SRI-4. Adjusting for baseline values using the ratio of change to baseline revealed significant differences in CD4 + T cell immune profiles between responders and non-responders. ROC analysis confirmed a satisfactory performance of rash, renal involvement, percentage change of CD4 + T cells, and C3 in predicting SRI-4, yielding an AUC of 0.933. LLDAS analysis showed that hematological involvements and lower CLA + Treg were potent predictive markers in LLDAS attainment. Conversely, renal involvement failed to have significant association in achieving LLDAS. The analysis of background therapy in SLE patients showed that MMF was more likely to reach the SRI-4 response with the combination of Ld-IL2.ConclusionsThese findings uncovered the predictors of Ld-IL2 treatment efficacy in SLE patients and provided guidance to physicians for rational utilization.

Use of belimumab in treating patients with systemic lupus erythematosus: a single-center, real-world retrospective study

ObjectiveTo investigate the efficacy and safety of belimumab in the treatment of systemic lupus erythematosus (SLE) in a real-world setting and provide a valuable reference for clinical treatment.MethodsIn this retrospective study, 101 patients with SLE who came to our hospital from March 2020 to September 2022, 56 of whom with lupus nephritis (LN), were selected. All patients received belimumab in combination with standard of care(SoC)therapy regimen for more than 52 weeks and their clinical/laboratory data, assessment of disease activity, glucocorticoids dosage and occurrence of adverse events were recorded. Lupus Low Disease Activity State (LLDAS) and DORIS remission as a primary goal in the treatment of SLE. The groups were classified according to the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K): SLEDAI-2 K < 6 was categorized as the mild group (mild activity) and SLEDAI-2 K ≥ 6 was categorized as the active group (moderate-severe activity). The disease of the two groups mentioned above were assessed using the SELENA-SLEDAI Flare Index (SFI) and the SLE Responder Index-4 (SRI-4), respectively. Furthermore, we used complete remission (CR) and partial remission (PR) in the kidney as the standard for efficacy evaluation for LN patients.ResultsAfter 52 weeks of treatment with belimumab, patients’ complement levels increased significantly (p < 0.05); Other indicators such as 24-hour urine protein quantification and daily glucocorticoids dose decreased compared to pretreatment (p < 0.05). At 52 weeks, (i) after evaluation, the whole group of patients showed significant improvement in their condition; (ii) 55.4% of patients achieved LLDAS and 23.8% achieved DORIS remission; (iii) 73.2% of patients with LN achieved CR, 16.1% achieved PR. Adverse reactions were observed in 15 patients (14.9%), all of which normalized after symptomatic treatment.ConclusionsIn general, during treatment with belimumab, immunological and biochemical indices improved in SLE patients, urinary protein levels were reduced in LN patients, and the rate of renal function remission was effectively increased; At the same time, the use of belimumab is associated with a low frequency of side effects, good overall tolerability and a favorable safety profile.

Baricitinib in the treatment of systemic lupus erythematosus: a systematic review of randomized controlled trials.

Baricitinib, a Janus Kinase (JAK) inhibitor, has emerged as a potential therapeutic option for systemic lupus erythematosus (SLE). This systematic review aims to synthesize evidence from randomized controlled trials (RCTs) evaluating the potential of baricitinib in treating SLE. A systematic search was conducted across electronic databases to identify relevant RCTs assessing baricitinib in patients with SLE. Studies reporting outcomes such as the Systemic Lupus Erythematosus Responder Index-4 (SRI-4), adverse events, and safety profiles were included. Data extraction and quality assessment were performed following PRISMA guidelines. A total of four studies were evaluated for efficacy and safety of baricitinib therapy. Three studies reported SRI-4, British Isles Lupus Assessment Group (BILAG), and Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K), except for Dorner and colleagues Only Dorner and colleagues and Wallace and colleagues discuss the anti-dsDNA titres following treatment with baricitinib. The findings consistently demonstrated improved efficacy of baricitinib compared to placebo, particularly in terms of SRI-4 scores. Higher dosages of baricitinib showed significant improvement in disease activity and severity indices. Adverse events, including infections and gastrointestinal disturbances, were reported. Baricitinib holds promise for treating SLE, but caution is needed due to potential adverse events. Careful patient selection and monitoring are crucial. Future research should prioritize long-term safety and comparative effectiveness studies to better understand baricitinib's role in managing SLE.

Evaluation of the Efficacy and Safety of Anifrolumab in Moderate-to-Severe Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease, which poses significant challenges due to its chronic nature and complex clinical manifestations.For patients with moderate-to-severe SLE, anifrolumab, a monoclonal antibody that targets the type 1 interferon receptor (IFNAR), has emerged as a cutting-edge treatment option that can reduce disease activity, prevent organ damage from the illness or side effects resulting from medications, and enhance the quality of life for those living with SLE. Consequently, this drug has received approval from major regulatory agencies. Anifrolumab's safety, effectiveness, and long-term results are assessed in this systematic review using information from clinical trials, real-world research, and retrospective analysis. In particular, clinical investigations, such as the MUSE Phase II and TULIP Phase III trials, showed that anifrolumab significantly improved important outcomescompared to placebo, including the SLE Responder Index, major clinical response, and disease activity ratings. During extended use, anifrolumab demonstrated significant sustained efficacy and a tolerable safety profile, with controllable side events mostly associated with viral infections. Moreover, subgroup analyses, demonstrating that Asian patients and individuals with a strong interferon gene profile are particularly responsive to anifrolumab, underscore the importance of customized treatment methods. Anifrolumab's safety and effectiveness were further validated by real-world data, particularly in patients who reached the Lupus Low Disease Activity State (LLDAS), where the drug decreased glucocorticoid consumption and disease activity. Overall, anifrolumab shows great promise as a treatment for moderate-to-severe SLE, providing significant efficacy together with a manageable safety profile. To fully explore its therapeutic potential and optimize therapy approaches for the management of SLE, further research is necessary, especially in lupus nephritis and other disease subsets.

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 of telitacicept in patients with lupus nephritis: a single-center, real-world retrospective study.

Telitacicept, an innovative drug used for the treatment of systemic lupus erythematosus (SLE), can effectively control disease progression and achieve favorable outcomes. While case reports have mentioned the use of Telitacicept in lupus nephritis (LN) treatment, its safety and efficacy in treating patients with LN have not been explored. Therefore, in this study, we aimed to evaluate the safety and efficacy of Telitacicept in managing patients with LN. In a single-center, real-world retrospective study, 30 LN patients with poor response or adverse reactions to conventional glucocorticoids at our Hospital were enrolled to receive Telitacicept. Patients were administered 160mg of Telitacicept subcutaneously once a week for at least 24weeks in addition to standard treatment. We assessed the SLE responder index-4 (SRI-4) at the beginning and the end of the treatment period, measured laboratory test indicators at 3, 6, and 9months, and observed the occurrence of adverse events in these patients. The SRI-4 response rate was 86.67% (n = 26), with a significantly lower systemic lupus erythematosus disease activity index (SLEDAI) score compared to the baseline. Post Telitacicept treatment, glucocorticoid intake of patients with LN significantly reduced from 50 (IQR:40, 51.25) at baseline to 10 (IQR:5,10) at the endpoint (Z = -6.547, p < 0.001). Patients with LN showed significantly improved urine occult blood levels after Telitacicept therapy. While the complement (C3 and C4) contents increased, immunoglobulins (IgG, IgA and IgM) reduced markedly (p < 0.001). The negative rate of dsDNA reached 26.67% and adverse events were alleviated post treatment. Only two cases of LN-related adverse reactions were reported, including herpes and infectious fever, respectively. Telitacicept primarily serves as an agent for the induction of remission therapy, with an attainment of complete remission rate standing at a commendable 73.3%. Telitacicept treatment reduced disease severity in patients with LN. The initial clinical trial provided supportive evidence for the effectiveness and safety of Telitacicept as a viable treatment option for LN, allowing a reduction in the daily glucocorticoid intake while maintaining a good safety profile, and improving hypocomplementation in LN management.

Evaluation of RNase therapy in systemic lupus erythematosus: a randomised phase 2a clinical trial of RSLV-132

BackgroundCirculating, extracellular RNA is the primary trigger of type I interferon in systemic lupus erythematosus (SLE), and interferon is known to play a central pathogenic role in the disease. RSLV-132...

Safety and efficacy of telitacicept in refractory systemic lupus erythematosus patients who failed treatment with belimumab : Acase series.

This study aimed to determine the effect and safety of telitacicept, an antagonist of BLyS/APRIL-mediated Bcell activation, in patients with systemic lupus erythematosus (SLE) who failed treatment with belimumab and in whom telitacicept was administered combined with conventional therapy. Areview of published reports on telitacicept for SLE was also performed. Aretrospective review was performed of the records of patients seen in the Department of Rheumatology at the Wuhan Hospital of Chinese and Western Medicine, Wuhan, China, with refractory SLE who had failed treatment with belimumab. The terms "systemic lupus erythematosus" and "telitacicept" were used to identify patients reported in the English medical literature. Identified were 14refractory SLE patients, 3males (21%) and 11females(79%). The median age was 32.9years. The median disease duration was 8.9years. Patients in this cohort received telitacicept for an average of 34.1weeks (17-62weeks) and the total SLE responder index4 (SRI-4) response rate was 78.9% (n = 11). The mean SLE Disease Activity Index (SLEDAI) score declined from 8.6 at baseline (95% confidence interval [CI] 7.87-9.28) to 4.29 at the endpoint (95% CI 3.4-5.16). All cases (100%) had hypocomplementemia at baseline, and 7cases (50%) reported normal C3 and C4 levels at the follow-up endpoint. At the observation endpoint, the 24‑h urinary protein value of the 13cases with proteinuria (baseline 24‑h urinary protein > 0.5 g/d) displayed areduction, and 3values turned negative. Although some patients had low serum total immunoglobulin (Ig) levels, subnormal IgG levels, and absolute counts of peripheral blood lymphocytes after treatment, no serious infection was reported. One case was refractory lupus hepatitis confirmed by liver pathology, and upon change to change to telitacicept treatment, liver function returned to normal. This is the first case series in SLE patients who accepted telitacicept treatment after failed treatment with belimumab. Our case series and review of the literature show that telitacicept combined with the original standard treatment may significantly improve disease activity while reducing prednisone use. No major safety issues were seen in this group of patients. Telitacicept may be apromising drug for the treatment of refractory lupus hepatitis.

Efficacy and safety of intravenous belimumab in a subgroup of South Korean patients with systemic lupus erythematosus enrolled into a Phase 3, randomized, placebo-controlled trial in North East Asia.

This post hoc analysis evaluated the efficacy and safety of intravenous belimumab 10 mg/kg in the South Korean subgroup of patients with systemic lupus erythematosus (SLE) enrolled in the North East Asia (NEA) study (GSK Study BEL113750; NCT01345253). NEA was a double-blind, placebo-controlled, randomized Phase 3 trial. Patients with active, autoantibody-positive SLE were randomized 2:1 to belimumab or placebo plus standard therapy administered on Days 0, 14, and 28, and then every 28 days up to Week 48. The primary efficacy endpoint in this analysis was SLE Responder Index 4 (SRI-4) response rate at Week 52, defined as the proportion of patients achieving a ≥4-point reduction in Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score, no worsening (<0.3 increase from baseline) in Physician Global Assessment, no new British Isles Lupus Assessment Group (BILAG) A domain and <2 new BILAG B domain scores. Among 100 South Korean patients enrolled in NEA, 54/66 (81.8%) belimumab- and 24/34 (70.6%) placebo-treated patients completed the double-blind phase. Significantly more belimumab- than placebo-treated patients achieved SRI-4 response at Week 52 (n = 35/66, 53.0% vs. n = 8/34, 23.5%; odds ratio [OR; 95% confidence interval (CI)]: 3.67 [1.45, 9.28]; p = .0061). The proportion of patients experiencing ≥1 adverse event was similar between groups (belimumab: n = 60/66, 90.9% vs. placebo: n = 31/34, 91.2%). No new safety signals emerged in this subgroup analysis. Belimumab was efficacious for the treatment of SLE and well tolerated among the South Korean subgroup of patients from the NEA study.

Telitacicept in patients with active systemic lupus erythematosus: results of a phase 2b, randomised, double-blind, placebo-controlled trial

ObjectivesThis phase 2b, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of telitacicept, a novel fusion protein that neutralises signals of B lymphocyte stimulator and a proliferation-inducing ligand, in...

Model-based meta-analysis using latent variable modeling to set benchmarks for new treatments of systemic lupus erythematosus.

Several investigational agents are under evaluation in systemic lupus erythematosus (SLE) clinical trials but quantitative frameworks to enable comparison of their efficacy to reference benchmark treatments are lacking. To benchmark SLE treatment effects and identify clinically important covariates, we developed a model-based meta-analysis (MBMA) within a latent variable model framework for efficacy end points and SLE composite end point scores (BILAG-based Composite Lupus Assessment and Systemic Lupus Erythematosus Responder Index) using aggregate-level data on approved and investigational therapeutics. SLE trials were searched using PubMed and www.clinicaltrials.gov for treatment name, SLE and clinical trial as search criteria that resulted in four data structures: (1) study and investigational agent, (2) dose and regimen, (3) baseline descriptors, and (4) outcomes. The final dataset consisted of 25 studies and 81 treatment arms evaluating 16 different agents. A previously developed (K Goteti etal. 2022) SLE latent variable model of data from placebo arms (placebo + standard of care treatments) was used to describe aggregate SLE end points over time for the various SLE placebo and treatment arms in a Bayesian MBMA framework. Continuous dose-effect relationships using a maximum effect model were included for anifrolumab, belimumab, CC-220 (iberdomide), epratuzumab, lulizumab pegol, and sifalimumab, whereas the remaining treatments were modeled as discrete dose effects. The final MBMA model was then used to benchmark these compounds with respect to the maximal efficacy on the latent variable compared to the placebo. This MBMA illustrates the application of latent variable models in understanding the trajectories of composite end points in chronic diseases and should enable model-informed development of new investigational agents in 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.

Impact of telemedicine on disease activity assessment: A case-crossover study nested within a cohort of patients with systemic lupus erythematosus.

The utilisation of telemedicine has been rapidly growing among patients with rheumatic diseases, especially following the corona virus disease 2019 pandemic. Ease and convenience appear to dominate the reasons for this growth. However, the effects of this approach in patients with systemic lupus erythematosus (SLE) are yet to be revealed. In this study, we examined the effect of telemedicine on disease activity assessment and damage scores in patients with SLE. This case-crossover study was nested within a national prospective cohort of patients with SLE in Saudi Arabia. Patients with SLE were included if they fulfilled the Systemic Lupus International Collaborating Clinics classification criteria between March 2020 and March 2021 and were assessed at three time points with 3 months between assessments, according to the standardised protocol of this cohort. Telemedicine was conducted for the first evaluation, while in-person assessments were used at the second and third visits. The primary outcome was the difference in the SLE disease activity index 2000 (SLEDAI-2K) score. The primary analysis was conducted using the repeated measure model and adjusted for potential confounders, including demographics, medications, and changes in steroid doses. Several sensitivity analyses were conducted to mitigate selection and time-varying confounders. A total of 92 participants were included in this study. Most patients were females (88%), with a mean (±standard deviation [SD]) age of 36 (±13) years. The mean (±SD) disease activity scores at baseline were as follows: SLEDAI-2K, 5 (±5); SLE responder index, 3.8 (±3.5); Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index, 1 (±1). The mean difference in SLEDAI-2K score was -1.641 (95% confidence interval -2.773 to -0.510, p = 0.005*) between telemedicine and follow-up visits. The results were consistent in all sensitivity analyses. We found that telemedicine assessment was associated with a much higher disease activity score than subsequent assessments, which may suggest an overestimation of disease activity and later assessment accuracy. Cautious adoption has been suggested for SLE patients with active disease.

Efficacy and safety of telitacicept in patients with systemic lupus erythematosus: a multicentre, retrospective, real-world study

ObjectiveTo examine the efficacy and safety of telitacicept in the treatment of patients with SLE in everyday clinical practice.MethodsSeventy-two patients with active SLE who received telitacicept for more than 24...

Safety and efficacy of biological agents in the treatment of Systemic Lupus Erythematosus (SLE)

BackgroundTo determine the safety and efficacy of biological agents used in the treatment of systemic lupus erythematosus (SLE) in adults.MethodsSystematic review and meta-analysis following PRISMA guidelines.Data sourcesMEDLINE (through Pubmed), EMBASE, Cochrane library, Clinicaltrials.gov, Australianclinicaltrials.gov.au, ANZCTR.org.au and WHO International Clinical Trials Registry Platform for studies published from 20 May 2021 and 15 years prior. A grey literature search was performed and completed on 31 May 2021.Study criteriaPhase II, III or quasi randomised controlled trials, studies with only cerebral or cutaneous lupus were excluded. Data extraction: Two authors independently screened studies for eligibility, extracted, reviewed data for accuracy, and used the Cochrane tool to assess risk of bias.ResultsForty-four studies were identified, consisting of 15 groups of drugs and 25 different biological agents, totalling 16,889 patients. The main outcomes assessed included Systemic Lupus Erythematosus Responder Index (SRI), BILAG-Based Composite Lupus Assessment (BICLA) and combined combined/partial renal remission (CRR/PRR).Four groups of biologics were found to improve outcomes. Anti-interferons: Anifrolumab increased BICLA response and SRI 5 to 8, decreased prednisone dosages, with increased herpes zoster infections, but fewer serious adverse events. Sifalimumab improved SRI but also increased herpes zoster infections. Anti BAFF/BLyS and/or APRIL: Belimumab consistently improved SRI 4, decreased prednisone dosages, increased combined CRR/PRR, and had no adverse safety outcomes. Tabalumab increased SRI 5 at 52 weeks with no steroid sparing effect but was associated with increased infusion related adverse events. Telitacicept improved SRI 4 at 52 weeks, with no increased adverse events, though data was rather sparse. Anti CD-20 monoclonal antibody, Obinutuzumab increased combined CRR/PRR at 1 and 2 years. Anti IL12/23 monoclonal antibody, Ustekinumab, increased SRI 4 to 6, but not BICLA at 24 weeks, with no concerning safety outcomes.ConclusionMultiple biologic agents are shown in high quality studies to have a significant therapeutic impact on outcomes in SLE.

Selection of indicators reporting response rate in pharmaceutical trials for systemic lupus erythematosus: preference and relative sensitivity

ObjectiveSLE is a common multisystem autoimmune disease with chronic inflammation. Many efficacy evaluation indicators of randomised clinical trials (RCTs) for SLE have been proposed but the comparability remains unknown. We...

Does baricitinib reduce disease activity in patients with systemic lupus erythematosus? A systematic review and meta-analysis of randomized controlled trials.

Baricitinib is a selective Janus kinase inhibitor that has recently been approved for treating certain autoimmune disorders. This meta-analysis pooled the conflicting results from all published randomized controlled trials (RCTs) about the efficacy and safety of baricitinib in patients with systemic lupus erythematosus (SLE). We systemically searched four electronic databases. RCTs comparing baricitinib versus placebo were included. Our outcomes were pooled as the risk ratio (RR) in the random effects model. Our primary outcome was the proportion of patients who achieved a SLE Responder Index-4 (SRI-4) response. A total of three RCTs, comprising 1849 patients, were included. Baricitinib 4 mg was associated with a significantly higher proportion of patients who attained SRI-4 response at week 24 (RR = 1.19, 95% CI [1.05, 1.35], P < 0.01). However, this did not reach statistical significance with baricitinib 4 mg at week 52 and baricitinib 2 mg at both week 24 and week 52 (RR = 1.13, 95% CI [0.96, 1.34], P = 0.15; RR = 1.09, 95% CI [0.96, 1.24], P = 0.20; RR = 1.05, 95% CI [0.92, 1.19], P = 0.50, respectively). The risk for serious infections was higher in the baricitinib 4 mg group (RR = 2.23, 95% CI [1.13, 4.37], P = 0.02). Baricitinib 2 mg did not show any clinical benefit. In contrast, baricitinib 4 mg might have the potential to reduce SLE disease activity; however, further research is required to evaluate its long-term efficacy. Until higher-quality evidence is developed, the benefits and risks of baricitinib should be considered before initiating its therapy. Key Points • Baricitinib is a selective Janus kinase inhibitor that has recently been approved for treating certain autoimmune disorders; however, its efficacy in patients with systemic lupus erythematosus (SLE) is still inconclusive. • In our meta-analysis, baricitinib 2 mg did not show any clinical benefit. In contrast, baricitinib 4 mg significantly reduced SLE activity in terms of SRI-4 response at week 24. However, this did not reach statistical significance at week 52. • Further studies are required to investigate the long-term efficacy of baricitinib 4 mg in patients with SLE.

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...

Sensitivity analysis of EQ-5D-3L index scores in terms of discriminative and known-groups validity in SLE: introducing Adequate Health State.

To investigate the ability of different EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) index scores to discriminate between verum drug and placebo (discriminant validity) as well as between responders and non-responders (known-groups validity) in the SLE patient population of two phase III clinical trials of belimumab. Data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials (N = 1684), which both showed superiority of belimumab to placebo, were utilized. Responders were defined as SLE Responder Index 4 (SRI-4) achievers at week 52. The Pearson's χ2 and Mann-Whitney U tests were used for comparisons, and logistic regression analysis was used for adjustments for confounders and assessment of independence. While full health state (FHS; EQ-5D index score 1) showed the best ability to discriminate between belimumab and placebo [adjusted odds ratio (OR) 1.47; 95% CI 1.11, 1.96; P = 0.008] and between SRI-4 responders and non-responders (adjusted OR 3.47; 95% CI 1.29, 10.98; P = 0.020), the discriminative ability of EQ-5D index scores 0.800 or more reached statistical significance for both discriminant validity (adjusted OR 1.29; 95% CI 1.02, 1.63; P = 0.036) and known-groups validity (adjusted OR 3.08; 95% CI 1.16, 9.69; P = 0.034). Overall, higher EQ-5D index scores were associated with increasing ability to discriminate between belimumab and placebo, and between responders and non-responders. EQ-5D index scores less stringent than FHS may be clinically relevant health-related quality of life goals of treatment in patients with SLE, introducing the concept of EQ-5D adequate health state when FHS is not achievable.