ACR20 Response Research Articles

Comparative efficacy and safety of bimekizumab in psoriatic arthritis: a systematic literature review and network meta-analysis.

To understand the relative efficacy and safety of bimekizumab, a selective inhibitor of IL-17F in addition to IL-17A, vs other biologic and targeted synthetic DMARDs (b/tsDMARDs) for PsA using network meta-analysis (NMA). A systematic literature review (most recent update conducted on 1 January 2023) identified randomized controlled trials (RCTs) of b/tsDMARDs in PsA. Bayesian NMAs were conducted for efficacy outcomes at Weeks 12-24 for b/tsDMARD-naïve and TNF inhibitor (TNFi)-experienced patients. Safety at Weeks 12-24 was analysed in a mixed population. Odds ratios (ORs) and differences of mean change with the associated 95% credible interval (CrI) were calculated for the best-fitting models, and the surface under the cumulative ranking curve (SUCRA) values were calculated to determine relative rank. The NMA included 41 RCTs for 22 b/tsDMARDs. For minimal disease activity (MDA), bimekizumab ranked 1st in b/tsDMARD-naïve patients and 2nd in TNFi-experienced patients. In b/tsDMARD-naïve patients, bimekizumab ranked 6th, 5th and 3rd for ACR response ACR20/50/70, respectively. In TNFi-experienced patients, bimekizumab ranked 1st, 2nd and 1st for ACR20/50/70, respectively. For Psoriasis Area and Severity Index 90/100, bimekizumab ranked 2nd and 1st in b/tsDMARD-naïve patients, respectively, and 1st and 2nd in TNFi-experienced patients, respectively. Bimekizumab was comparable to b/tsDMARDs for serious adverse events. Bimekizumab ranked favourably among b/tsDMARDs for efficacy on joint, skin and MDA outcomes, and showed comparable safety, suggesting it may be a beneficial treatment option for patients with PsA.

Comparative Effectiveness of Bimekizumab in Psoriatic Arthritis: A Model-Based Meta-Analysis of American College of Rheumatology Response Criteria.

A model-based meta-analysis (MBMA) was conducted to compare the efficacy of bimekizumab with other psoriatic arthritis (PsA) treatment regimens using ≥ 20%/50%/70% improvements in American College of Rheumatology (ACR) criteria (ACR20/50/70) for patients with PsA. Forty-nine trials of 16 drugs were identified in the literature, comprising 21,340 patients. Trial-level covariates, including prior biologic use, concomitant methotrexate use, time since diagnosis, trial completion year, and active comparator were considered for exploratory models. The final model was selected using leave-one-out cross-validation (LOO CV) to assess predictive performance based on prespecified criteria. LOO CV was conducted for 15 trials; the final model demonstrated that 91.5% (952/1,040) of the observed treatment differences, and 96.1% of the observed ACR20/50/70 response rates were within the 95% prediction interval (PI). Median ACR50 response rates (95% PI) at week 16 in biologic-naïve patients were predicted to be 44% (40-49%) for bimekizumab 160 mg, among the highest of all treatments analyzed. Response rates for secukinumab 150 mg and risankizumab 150 mg were 28% (25-32%) and 27% (24-31%), respectively. The MBMA was also used to predict the probability of success (PoS) of potential head-to-head trials using ACR50 response as the end point with varying sample sizes: vs. secukinumab 150 mg, the PoS for bimekizumab 160 mg was 62% (N = 200) and 90% (N = 400). Versus risankizumab 150 mg, the PoS for bimekizumab 160 mg was 68% (N = 200) and 94% (N = 400). In summary, a predictive MBMA described ACR20/50/70 outcomes in PsA, allowing accurate and precise treatment comparisons and robust PoS calculations.

Lower body mass and lower adiposity are associated with differential responses to two treatment strategies for rheumatoid arthritis

PurposeTo determine if body mass index (BMI) and adipokine levels identify rheumatoid arthritis (RA) patients most likely to benefit from initiation of tumour necrosis factor inhibitors (TNFi) after methotrexate inadequate...

Comparing tocilizumab biosimilar BAT1806/BIIB800 with reference tocilizumab in patients with moderate-to-severe rheumatoid arthritis with an inadequate response to methotrexate: a phase 3, randomised, multicentre, double-blind, active-controlled clinical trial

Biosimilars provide an opportunity to address unmet medical need by expanding access to biological treatments. This study aimed to show equivalent efficacy, and comparable safety, immunogenicity, and pharmacokinetic profiles of a proposed tocilizumab biosimilar BAT1806/BIIB800, to reference tocilizumab, in participants with rheumatoid arthritis with an inadequate response to methotrexate. This phase 3, multicentre, randomised, double-blind, active-controlled, equivalence study comprised a 24-week initial treatment period (results reported here) and a 24-week secondary treatment period. Participants were recruited at 54 centres across five countries (China, Ukraine, Poland, Georgia, and Bulgaria). Patients with active rheumatoid arthritis with an inadequate response to methotrexate were randomly assigned (1:1:2) to receive reference tocilizumab up to week 48, or reference tocilizumab up to week 24 followed by BAT1806/BIIB800 up to week 48 (the two reference tocilizumab groups were analysed as a single group in this analysis), or BAT1806/BIIB800 up to week 48 (the BAT1806/BIIB800 group), administered by intravenous infusion once every 4 weeks at a starting dose of 8 mg/kg. The primary endpoint was the proportion of participants who had a 20% improvement in American College of Rheumatology criteria (ACR20) at week 12 (for the European Medicines Agency [EMA]) or week 24 (for the US Food and Drug Administration [FDA] and China National Medical Products Administration [NMPA]) using prespecified equivalence margins (95% CI -14·5 to +14·5 [EMA], 90% CI -12·0 to +15·0 [FDA], and 95% CI -13·6 to +13·6 [NMPA]). The International Council for Harmonisation E9(R1) estimand framework, with strategies for addressing intercurrent events, was implemented for the efficacy evaluations with expected differences as per the predefined equivalence margins. This trial is registered at ClinicalTrials.gov (NCT03830203) and EudraCT (2018-002202-31), and is closed to new participants. Between Dec 19, 2018, and Jan 5, 2021, we randomly assigned 621 participants: 309 to the reference tocilizumab group and 312 to the BAT1806/BIIB800 group. The mean age was 50·5 years (SD 12·0), 534 (86%) were women, 87 (14%) were men, and 368 (59%) were White. For the primary estimands, estimated ACR20 response rates were 64·8% in the reference tocilizumab group and 69·0% in the BAT1806/BIIB800 group (treatment difference 4·1% [95% CI -3·6 to 11·9]) at week 12, and 67·9% in the reference tocilizumab group and 69·9% in the BAT1806/BIIB800 group (treatment difference 1·9% [90% CI -4·0 to 7·9; 95% CI -5·2 to 9·1]) at week 24. All confidence intervals were contained within the predefined equivalence margins. Comparable pharmacokinetic and immunogenicity profiles were observed for the reference tocilizumab and BAT1806/BIIB800 groups. Adverse events were reported by 201 (65%) participants in the reference tocilizumab group and 206 (66%) in the BAT1806/BIIB800 group; 196 (63%) participants in the reference tocilizumab group and 201 (64%) participants in the BAT1806/BIIB800 group reported a treatment-emergent adverse event. Five participants had a fatal event (reference tocilizumab n=1; BAT1806/BIIB800 n=4). BAT1806/BIIB800 showed equivalent efficacy, and comparable safety, immunogenicity, and pharmacokinetic profiles as reference tocilizumab. Bio-Thera Solutions and Biogen.

Sex-related differences in patient characteristics, and efficacy and safety of advanced therapies in randomised clinical trials in psoriatic arthritis: a systematic literature review and meta-analysis

Sex-related differences in clinical manifestations and disease outcomes exist in psoriatic arthritis, however, there is limited information on sex-related differences in randomised controlled trials of psoriatic arthritis. We aimed to compare patient characteristics and efficacy and safety of advanced therapies (including biological and targeted synthetic therapies) between male and female patients with psoriatic arthritis participating in randomised controlled trials. In this systematic review and meta-analysis, we searched Medline, Embase, and Central databases, and conference abstract archives, from their inception to June 10, 2022, for randomised controlled trials that assessed the efficacy of advanced therapies in psoriatic arthritis. Two reviewers extracted information on participants' characteristics and rates of American College of Rheumatology (ACR) 20 and ACR50 response and minimal disease activity (MDA) by sex. Random-effects models were used to calculate pooled effects of ACR20, ACR50, and MDA in male versus female patients by drug class. We included 54 trials (11 514 [50·9%] of 22 621 participants were female and 11 107 [49·1%] were male). Sex-disaggregated results were reported in a minority of studies (nine [17%] of 54 reported baseline characteristics by sex, 18 [33%] reported efficacy by sex, and two [4%] reported safety endpoints by sex). At baseline, male patients had lower baseline tender joint count (mean difference -3·01 [95% CI -3·83 to -2·18], health assessment questionnaire scores (-0·28 [-0·33 to -0·24]), pain scores (-4·58 [-6·86 to -2·30]), patient global assessment (-3·22 [-5·27 to -1·17]), and physician global assessment (-1·34 [-2·08 to -0·08]) than did female patients. Male patients had higher baseline psoriasis area and severity index scores (mean difference 1·95 [95% CI 0·78 to 3·11]) and C-reactive protein concentrations (2·57 [0·40 to 4·74]) than did female patients. ACR20 response by sex varied across drug classes, with higher rates in males than females with interleukin (IL)-17 inhibitors (odds ratio [OR] 1·70 [95% CI 1·38-2·11]), IL-23 inhibitor (1·46 [1·20-1·78]), IL-12 and IL-23 inhibitor (2·67 [1·39-5·09]), and tumour necrosis factor (TNF) inhibitors (1·55 [1·11-2·18]), but no difference with JAK and TYK2 inhibitors (1·10 [0·87-1·38]). Similarly, ACR50 response rates were higher in male patients versus female patients in all drug classes, with exception of JAK and TYK2 inhibitors (TNF inhibitors, OR 2·17 [95% CI 1·62-2·90]; IL-17 inhibitors, 1·93 [1·56-2·38]; IL-23 inhibitor, 1·71 [1·25-2·34]; IL-12 and 23 inhibitor, 2·43 [1·14-5·20]; and JAK and TYK2 inhibitors, 1·09 [0·73-1·62]). Male patients were more likely to reach MDA with most drug classes, including IL-17 inhibitors (OR 1·99 [95% CI 1·50-2·63]), IL-23 inhibitors (1·79 [1·29-2·50]), TNF inhibitors (2·62 [1·54-4·44]), and JAK and TYK2 inhibitors (1·77 [1·15-2·73]). Risk of bias was low for most studies. Biological sex of patients with psoriatic arthritis influences their response to advanced therapies, but the effect varies by drug class. Selective reporting might have influenced these results. Future trials should report baseline characteristics and endpoint results by sex. Canadian Rheumatology Association.

Impact of hyperuricaemia on patients with psoriatic arthritis treated with secukinumab in the FUTURE 2–5 and MAXIMISE studies

ObjectivesPatients with psoriatic arthritis (PsA) are at a significantly increased risk of hyperuricaemia and development of gout, and those with hyperuricaemia have been found to respond poorly to PsA treatment...

Safety and efficacy of peficitinib in Asian patients with rheumatoid arthritis who had an inadequate response or intolerance to methotrexate: results of a multicenter, randomized, double-blind, placebo-controlled phase 3 study

The efficacy and safety of the oral Janus kinase inhibitor peficitinib were investigated in Asian patients with rheumatoid arthritis (RA). In this double-blind, phase 3 study, patients from mainland China, Korea, and Taiwan with RA and an inadequate response/intolerance to methotrexate were randomized (1:1:1) to once-daily placebo (N=128), peficitinib 100mg(N=129), or 150mg(N=128) in combination with non-biologic DMARDs. At Week 24, patients receiving placebo switched to peficitinib 100mg or 150mg. American College of Rheumatology (ACR) 20 response at Week 24/early termination (ET) was the primary endpoint. Adverse events (AEs) were assessed. The study was registered at ClinicalTrials (NCT03660059). 385 patients were included in the analysis. ACR20 responses were statistically significantly higher in both peficitinib 100mg (56.6%) and 150mg (56.3%) groups versus placebo (24.2%); Odds Ratio (95% confidence interval, CI) 4.14 (2.42, 7.08) and 4.07 (2.38, 6.96), respectively (both P<0.001) at Week 24/ET. The incidence rate of herpes zoster related disease (herpes zoster and varicella) was higher in patients who received peficitinib versus placebo, but no dose dependency was observed (incidence rate/100 patient-years (95% CI): peficitinib 6.7 (4.32, 10.37); placebo 3.7 (0.93, 14.88). In Asian patients with RA and an inadequate response/intolerance to methotrexate, peficitinib 100mg and 150mg demonstrated superiority to placebo in the reduction of RA symptoms and was well tolerated. No additional benefit was observed with use of the higher peficitinib dose in this study population of predominantly Chinese patients. Astellas Pharma.

Determination of the most appropriate ACR response definition for contemporary drug approval trials in rheumatoid arthritis

ObjectivesTo evaluate which American College of Rheumatology (ACR) response definition (ACR20, 50 or 70) should primarily be used for efficacy claims in future drug approval trials of rheumatoid arthritis (RA).MethodsWe...

Anti-GM-CSF otilimab versus tofacitinib or placebo in patients with active rheumatoid arthritis and an inadequate response to conventional or biologic DMARDs: two phase 3 randomised trials (contRAst 1 and contRAst 2)

ObjectivesTo investigate the efficacy and safety of otilimab, an antigranulocyte-macrophage colony-stimulating factor antibody, in patients with active rheumatoid arthritis.MethodsTwo phase 3, double-blind randomised controlled trials including patients with inadequate responses...

Anti-GM-CSF otilimab versus sarilumab or placebo in patients with rheumatoid arthritis and inadequate response to targeted therapies: a phase III randomised trial (contRAst 3)

ObjectivesTo investigate the efficacy and safety of otilimab, an anti-granulocyte-macrophage colony-stimulating factor antibody, in patients with active rheumatoid arthritis and an inadequate response to conventional synthetic (cs) and biologic disease-modifying...

Effect of guselkumab on serum biomarkers in patients with active psoriatic arthritis and inadequate response to tumor necrosis factor inhibitors: results from the COSMOS phase 3b study

BackgroundGuselkumab is a selective interleukin (IL)-23 inhibitor targeting the IL-23p19 subunit. In the phase 3b COSMOS trial, guselkumab demonstrated efficacy in treating participants with active psoriatic arthritis (PsA) and inadequate response (IR; lack of efficacy or intolerance) to tumor necrosis factor inhibitors (TNFi).MethodsAdults with active PsA (≥ 3 swollen joints, ≥ 3 tender joints) and IR to one or two TNFi (TNFi-IR) were randomized 2:1 to guselkumab at Weeks 0, 4, then every 8 weeks (Q8W) or placebo➔guselkumab Q8W at Week 24 with possible early escape at Week 16. Levels of serum cytokines, including interferon γ (IFNγ), IL-10, and tumor necrosis factor α (TNFα); T helper 17 (Th17) effector cytokines IL-17A, IL-17F, and IL-22; and acute phase proteins C-reactive protein (CRP), IL-6, and serum amyloid A (SAA), were assessed and compared with demographically matched healthy controls; guselkumab pharmacodynamics through Week 24 were also assessed. Associations between baseline biomarker levels and 1) baseline disease activity (28-joint disease activity score using CRP [DAS28-CRP], psoriasis area and severity index [PASI], and % body surface area [BSA] affected by psoriasis) and 2) clinical response (including ≥ 20% improvement in American College of Rheumatology criteria [ACR20] response) at Week 24 were assessed.ResultsBaseline serum levels of IL-6, IL-10, IL-17A, IL-17F, IL-22, TNFα, and IFNγ were significantly higher in COSMOS TNFi-IR participants than in healthy controls. Baseline IL-6, CRP, and SAA levels were associated with baseline DAS28-CRP. IL-17A and IL-17F levels were associated with baseline PASI score and psoriasis BSA. Baseline swollen or tender joint counts did not associate with baseline biomarker levels. At Week 24, significant decreases from baseline in CRP, SAA, IL-17A, IL-17F, and IL-22 levels were seen in guselkumab-, but not placebo-, treated participants. IL-17F and IL-22 levels at Week 24 in guselkumab-treated participants did not significantly differ from those of healthy controls. Guselkumab-treated participants achieving ACR20 response at Week 24 exhibited higher baseline IL-22 and IFNγ levels versus nonresponders.ConclusionsResults from COSMOS participants with active, TNFi-IR PsA suggest guselkumab reduces levels of effector cytokines associated with the IL-23/IL-17 pathway, including those associated with baseline arthritis and skin disease activity.Trial registrationClinicalTrials.gov: NCT03796858.

IL-23 Inhibitors to treat psoriatic arthritis: A systematic review & meta-analysis of randomized controlled trials

AimTo review the available evidence on the efficacy and safety profiles of four Interleukin-23 inhibitors in patients with Psoriatic Arthritis. MethodsSeveral databases were searched till July 2022. A total of 11 RCTs with at least one treatment arm were included. All articles were in English. The primary outcomes were ACR20, HAQ-DI, PASI90, and TEAEs experienced by the patients. ResultsCompared to other groups, Guselkumab had the strongest association with ACR20 response (RR: 2.14; 95% CI: 1.84-2.49, p < 0.00001), while a mean change in HAQ-DI (MD: -0.24; 95% CI: -0.41- -0.13, p = 0.0001) and PASI90 (RR: 9.81; 95% CI: 3.18-30.22; p <0.01) were most strongly associated with Ustekinumab. TEAEs were significantly present in the Guselkumab group (RR: 1.26; 95% CI: 1.00 - 1.59; p = 0.05). ConclusionAlthough our analysis suggests that IL-23 inhibitors are efficacious at treating psoriatic arthritis, further studies are required for long-term outcomes.

Compared efficacy of rituximab, abatacept, and tocilizumab in patients with rheumatoid arthritis refractory to methotrexate or TNF inhibitors agents: a systematic review and network meta-analysis

BackgroundOur aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents.MethodsWe searched 6 databases until January 2023 for phase 2–4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response.ResultsThe meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113–10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554–3.161, p < 0.001) for ACR70 compared to tocilizumab.ConclusionWe found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.

Efficacy and Safety of Tyrosine Kinase 2/Janus Kinase 1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial.

Brepocitinib is a tyrosine kinase 2/Janus kinase 1 inhibitor in development for treatment of several immunological diseases. Efficacy and safety of oral brepocitinib were assessed in participants with moderately-to-severely active psoriatic arthritis (PsA) for up to 52 weeks. This placebo-controlled, dose-ranging, phase IIb study randomized participants to brepocitinib 10 mg once daily (QD), 30 mg QD, 60 mg QD, or placebo, advancing to brepocitinib 30 or 60 mg QD at week 16. The primary endpoint was American College of Rheumatology (ACR)20 response rate at week 16. Secondary endpoints included response rates of ACR50/70, 75% and 90% improvement in Psoriasis Area and Severity Index (PASI75/90), and Minimal Disease Activity (MDA) at weeks 16 and 52. Adverse events (AEs) were monitored throughout. Overall, 218 participants were randomized and treated. At week 16, brepocitinib 30 and 60 mg QD groups had significantly greater ACR20 response rates (66.7% [P = 0.0197] and 74.6% [P = 0.0006], respectively), versus placebo (43.3%) and significantly higher ACR50/70, PASI75/90, and MDA response rates. Response rates were maintained or improved through week 52. AEs were mostly mild/moderate; serious AEs (15) in 12 (5.5%) participants included infections in 6 (2.8%) in brepocitinib 30 and 60 mg QD groups. No major adverse cardiovascular events or deaths occurred. Brepocitinib 30 and 60 mg QD were superior to placebo at reducing signs and symptoms of PsA. Brepocitinib was generally well tolerated throughout the 52-week study with a safety profile consistent with other brepocitinib clinical trials.

Benefits of probiotics in rheumatoid arthritis patients: A systematic review and meta analysis

Purpose: To determine the efficacy of probiotics in the treatment of rheumatoid arthritis (RA).&#x0D; Methods: Clinical trials were searched from online medicine databases. Outcomes such as changes in inflammatory cytokines and disability parameters such as American College of Rheumatology 20 % (ACR20) response, were analyzed.&#x0D; Results: Nine trials were eligible, and 385 patients were included. Meta-analysis showed that probiotic consumption significantly improved 28-joint disease activity (DAS28) score and decreased levels of high-sensitivity CRP (95 % CI = -3.23, -0.80; p = 0.001), tumor necrosis factor-α (95 % CI = -1.40, -0.67; p &lt; 0.00001), interleukin (IL)-1β (95 % CI = -11.37, -0.84; p = 0.02) and IL-12 (95 % CI = -94.91, -53.58; p &lt; 0.00001) in RA patients when compared with placebo. However, probiotics did not affect ACR20 response, erythrocyte sedimentation rate, IL-6, and IL-10, when compared with placebo.&#x0D; Conclusion: The effects of probiotic consumption on RA are very beneficial and have some reference significance for formulating treatment guidelines for RA. However, more trials are needed to confirm the influence of probiotics on RA patients. Furthermore, more clinical trials with larger sample sizes are needed to affirm the effectiveness of probiotics in mitigating disability and inflammatory status in RA patients.

Comparison of the efficacy and safety of olokizumab at different dosages in patients with active rheumatoid arthritis: anetwork meta-analysis of randomized controlled trials.

This study aimed to assess the relative efficacy and safety of olokizumab at different dosages in patients with active rheumatoid arthritis (RA). We performed aBayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of olokizumab administered intravenously to RA patients at 64 mg/kg every 2 or 4weeks (Q2 or Q4W). Five RCTs comprising 2609patients met the inclusion criteria. Both olokizumab Q2 and Q4W treatments achieved asignificant American College of Rheumatology 20% response (ACR20) compared with the placebo (odds ratio [OR] 3.21, 95% credible interval [CrI] 2.53-4.09; OR 3.05, 95% CrI 2.43-3.86). However, olokizumab Q2W was associated with the most favorable surface using the cumulative ranking curve (SUCRA) for the ACR20 response rate. The ranking probability based on the SUCRA indicated that olokizumab Q2W had the highest probability of being considered the best treatment option for achieving the ACR20 response rate, followed by olokizumab Q4W, adalimumab, and placebo. The ACR50 and 70response rates showed asimilar distribution pattern to the ACR20 response rate, except that olokizumab Q4W had ahigher-ranking probability than olokizumab Q2W for ACR50. The SUCRA rating likelihood of adverse events (AEs) and withdrawal due to AEs showed that aplacebo was likely to be the best intervention. Both olokizumab Q2 and Q4W were efficacious and well-tolerated treatments for active RA.

Therapeutic Equivalence of Biosimilar and Reference Biologic Drugs in Rheumatoid Arthritis

Biosimilar drugs are potentially lower-cost versions of biologics that may improve access to therapy. However, there is a lack of adequate systematic reviews demonstrating equivalence between these drugs for the treatment of rheumatoid arthritis (RA). To assess the efficacy, safety, and immunogenicity associated with biosimilars of adalimumab, etanercept, and infliximab compared with their reference biologics in patients with RA. MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials, and LILACS databases were searched from inception to September 2021. Head-to-head randomized clinical trials (RCTs) of biosimilars of adalimumab, etanercept, and infliximab and their biologic reference drugs for RA were assessed. Two authors independently abstracted all data. Meta-analysis was conducted with bayesian random effects using relative risks (RRs) for binary outcomes and standardized mean differences (SMDs) for continuous outcomes, with 95% credible intervals (CrIs) and trial sequential analysis. Specific domains were assessed for the risk of bias in equivalence and noninferiority trials. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Equivalence was tested using prespecified margins for the American College of Rheumatology criteria, with at least 20% improvement in the core set measures (ACR20) (ie, RR, 0.94 to 1.06), and for the Health Assessment Questionnaire-Disability Index (HAQ-DI) (ie, SMD, -0.22 to 0.22). Secondary outcomes included 14 items measuring safety and immunogenicity. A total of 25 head-to-head trials provided data on 10 642 randomized patients with moderate to severe RA. Biosimilars met equivalence with reference biologics in terms of ACR20 response (24 RCTs with 10 259 patients; RR, 1.01; 95% CrI, 0.98 to 1.04; τ2 = 0.000) and change of HAQ-DI scores (14 RCTs with 5579 patients; SMD, -0.04; 95% CrI, -0.11 to 0.02; τ2 = 0.002) considering prespecified margins of equivalence. Trial sequential analysis found evidence for equivalence for ACR20 since 2017 and HAQ-DI since 2016. Overall, biosimilars were associated with similar safety and immunogenicity profiles compared with reference biologics. In this systematic review and meta-analysis, biosimilars of adalimumab, infliximab, and etanercept were associated with clinically equivalent treatment effects compared with their reference biologics for the treatment of RA.

A Phase 2 Trial of Peresolimab for Adults with Rheumatoid Arthritis

BackgroundPeresolimab is a humanized IgG1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway. Stimulation of this pathway would be a novel approach to the treatment of patients with autoimmune or autoinflammatory diseases.MethodsIn this phase 2a, double-blind, randomized, placebo-controlled trial, we assigned, in a 2:1:1 ratio, adult patients with moderate-to-severe rheumatoid arthritis who had had an inadequate response to, a loss of response to, or unacceptable side effects with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) or to biologic or targeted synthetic DMARDs to receive 700 mg of peresolimab, 300 mg of peresolimab, or placebo intravenously once every 4 weeks. The primary outcome was the change from baseline to week 12 in the Disease Activity Score for 28 joints based on the C-reactive protein level (DAS28-CRP). The DAS28-CRP ranges from 0 to 9.4, with higher scores indicating more severe disease. The primary comparison was between the 700-mg group and the placebo group. Secondary outcomes included the percentages of patients with American College of Rheumatology 20 (ACR20), ACR50, and ACR70 responses — defined as improvements from baseline of 20%, 50%, and 70% or more, respectively, in the numbers of tender and swollen joints and in at least three of five important domains — at week 12.ResultsAt week 12, the change from baseline in the DAS28-CRP was significantly greater in the 700-mg peresolimab group than in the placebo group (least-squares mean change [±SE], −2.09±0.18 vs. −0.99±0.26; difference in change, −1.09 [95% confidence interval, −1.73 to −0.46]; P<0.001). The results of the analyses of secondary outcomes favored the 700-mg dose over placebo with respect to the ACR20 response but not with respect to the ACR50 and ACR70 responses. Adverse events were similar in the peresolimab and placebo groups.ConclusionsPeresolimab showed efficacy in a phase 2a trial in patients with rheumatoid arthritis. These results provide evidence that stimulation of the PD-1 receptor has potential efficacy in the treatment of rheumatoid arthritis. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT04634253.)

OA18 Smoking and high BMI are associated with reductions in TNF inhibitor response in psoriatic arthritis: results from 12 European countries

Abstract Background/Aims In axial spondyloarthritis, it has been shown that while some adverse lifestyle factors (smoking and high body mass index (BMI)) are less likely to respond to TNF inhibition (TNFi), those who drink alcohol are more likely to respond to treatment - a result currently unexplained, and unlikely to be causal. We aimed to investigate these associations in psoriatic arthritis (PsA) and to quantify the impact of lifestyle factors on TNFi treatment response. Methods Adults with PsA commencing TNFi were identified via the European Spondyloarthritis Research Collaboration Network (https://eurospa.eu). Participants were required to have data on lifestyle factors (smoking, alcohol consumption, and/or BMI) recorded within ±30 days of commencing TNFi. The relationship between lifestyle factors and treatment outcome (ACR-50 response criteria at 12 months) was assessed using logistic regression, adjusted for age, sex, country, year of TNFi initiation, disease duration and baseline disease activity (DAS28). The analysis was then repeated for other treatment response criteria: ACR-20, ACR-70, DAPSA28-remission, DAPSA68-remission and Minimal Disease Activity. Results From 12 PsA registries, 9409 participants were included, 21% of whom were current smokers, 54% drank alcohol, 38% were overweight and 29% were obese. Other baseline characteristics are shown in Table 1. Among smokers, 18% met ACR-50 response criteria at 12 months, versus 26% of non-smokers, an association that remained after adjusting for potential confounders (adjusted odds ratio: 0.59; 95%CI: 0.48-0.72). Participants who were overweight (adjusted odds ratio: 0.80; 0.64-0.99) or obese (0.57; 0.44-0.72) were also less likely to achieve treatment response, compared to patients of normal weight. Similar results were seen across other outcome measures. The proportion who achieved ACR-50 response did not differ between patients who did/did not consume alcohol (both 22%). Conclusion Smoking and high BMI were associated with substantial decreases in the likelihood of TNFi response. The addition of non-pharmacological therapy, including the modification of adverse lifestyle factors, may offer the potential to enhance treatment outcomes. For example, if 100 patients were able to give up smoking when commencing TNFi, an additional eight would achieve ACR-50 at 12 months. Previous findings regarding alcohol and treatment response in axSpA were not replicated in PsA. Disclosure G.T. Jones: None. O. Rotariu: None. B. Michelsen: None. B. Glintborg: None. B. Gudbjornsson: None. T.J. Love: None. D. Nordström: None. T. Sokka: None. J. Vencovský: None. P. Horák: None. Z. Rotar: None. M. Tomšič: None. M. van der Sande: None. M.J. Nissen: None. B. Möller: None. C. Codreanu: None. J.K. Wallman: None. K.M. Fagerli: None. S.H. Rasmussen: None. L.M. Ørnbjerg: None. M.J. Santos: None. P. Carvalho: None. M.L. Hetland: None. M. Østergaard: None. G.J. Macfarlane: None.

Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study

Objectives To assess the efficacy and safety of olokizumab (OKZ), a monoclonal antibody against the interleukin-6 (IL-6) cytokine, versus placebo (PBO) in patients with prior inadequate response to tumour necrosis factor inhibitors (TNFi-IRs).Methods In this 24-week multicentre, placebo-controlled, double-blind study, the patients were randomised in a 2:2:1 ratio to receive subcutaneously administered OKZ 64 mg once every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w) or PBO plus methotrexate. At week 16, the patients on PBO were randomised to receive either OKZ regime. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. Disease Activity Score 28-joint count C-reactive protein (DAS28 (CRP)) &lt;3.2 at week 12 was the major secondary efficacy endpoint. Safety and immunogenicity were assessed.Results In 368 patients randomised, ACR20 response rates were 60.9% in OKZ q2w, 59.6% in OKZ q4w and 40.6% in PBO (p&lt;0.01 for both comparisons). Achievement of DAS28 (CRP) &lt;3.2 was significantly different, favouring the OKZ arms. Improvements in efficacy and patientreported outcomes were maintained throughout 24 weeks and were noted after week 16 in patients who switched from PBO.Dose-related treatment-emergent serious adverse events were 7% in OKZ q2w, 3.2% in OKZ q4w and none in the PBO group.Conclusions Direct inhibition of IL-6 with OKZ resulted in significant improvements in the signs and symptoms of rheumatoid arthritis compared with PBO in TNFi-IR patients with a similar safety profile as observed for monoclonal antibodies to the IL-6 receptor.