Biologics or tofacitinib for people with rheumatoid arthritis unsuccessfully treated with biologics: a systematic review and network meta-analysis.
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ABSTRACT:
SUBMITTER: Singh JA
PROVIDER: S-EPMC6472522 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC6481641 | biostudies-literature
Project description:Biologics have emerged as an effective treatment of rheumatoid arthritis (RA). However, there is a significant proportion of patients who fail to respond to biologics. Identifying the predictors that affect the response to biologics remains challenging. A comprehensive literature search of PubMed, Embase, and Web of Science databases was conducted through May 1, 2022. We included all studies that used a multivariate model to assess for the predictors of remission in RA patients treated with biologics. We calculated pooled odds ratios (OR) with 95% confidence intervals (CI) for risk factors reported in ≥ 3 studies using a random-effects model. A total of 16,934 patients with RA who were treated with biologics were included in twenty-one studies. Our study showed that old age (OR 0.98 (0.97, 0.99), P < 0.00001), female gender (OR 0.66 (0.56, 0.77), P < 0.00001), smoking history (OR 0.86 (0.75, 0.99), P 0.04), obesity (OR 0.95 (0.91, 0.99), P 0.02), poor functional status (OR 0.62 (0.48, 1.27), P < 0.00001), high disease activity (OR 0.90 (0.85, 0.96), P 0.0005), and elevated erythrocyte sedimentation rate (OR 0.99 (0.98, 1.00), P 0.009) were poor predictors of remission. On the other hand, positive anti-citrullinated protein antibodies (OR 2.52 (1.53, 4.12), P 0.0003) was associated with high remission rate. Old age, female gender, obesity, smoking history, poor functional status, high disease activity, and elevated ESR at the time of diagnosis have been associated with poor response to biologics. Our findings could help establish a risk stratification model for predicting the remission rate in RA patients receiving biologics.
| S-EPMC9652218 | biostudies-literature
Project description: Not available
| S-EPMC7068903 | biostudies-literature
Project description:Recently, serious infections related to the use of tofacitinib (TOF) for treatment of rheumatoid arthritis (RA) have raised considerable interest. This study aimed to compare the risk for serious infections in patients with RA upon receiving TOF versus biologic disease-modifying antirheumatic drugs (bDMARDs) by age at treatment initiation. We identified adult RA patients exposed to TOF or bDMARDs using data collected by the Swiss registry for inflammatory rheumatic diseases (SCQM) from 2015 to 2018. The event of interest was the first non-fatal serious infection (SI) during drug exposure. Missing or incomplete SI dates were imputed as either the lower (left) or upper (right) limit of the known occurrence interval. The ratio of SI hazards (HR) of TOF versus bDMARDs was estimated as a function of age using covariate-adjusted Cox regression applied to each type of imputed time-to-SI. A total of 1687 patients provided time at risk for a first SI during study participation and drug exposure for 2238 different treatment courses, 345 for TOF and 1893 for bDMARDs. We identified 44 (left imputation) or 43 (right imputation), respectively, first SIs (12/12 on TOF versus 32/31 on bDMARDs). Left and right imputation produced similar results. For patients aged ≥ 69 years, the treatment HR started to be increased (lower limit of 95% confidence intervals (LLCIs) > 1). By the age of 76, the difference between TOF and bDMARDs started to be clinically relevant (LLCIs > 1.25). For patients aged < 65 years, the data were insufficient to draw conclusions. Our results suggest that we should expect an increased risk for SIs in older patients treated with TOF compared to bDMARDs supporting a cautious use of TOF in these patients.
| S-EPMC10584888 | biostudies-literature
Project description:ObjectivesThis study aims to compare the disease status of patients with active rheumatoid arthritis (RA) after treatment with tofacitinib or non- tumor necrosis factor (TNF) biologics.Patients and methodsThe study included a total of 50 RA patients (18 males, 32 females; mean age 68.3±1.3 years; range 42 to 92 years). We prospectively and randomly enrolled 25 patients for treatment with tofacitinib (Tofa group: 10 males, 15 females; mean age 68.3±2.0 years; range, 42 to 92 years) and 25 for treatment with non-TNF biologics (non-TNF group: 8 males, 17 females; mean age 68.3±1.7 years; range 51 to 92 years). Mean disease activity score 28 (DAS28), C-reactive protein (CRP), clinical disease activity index (CDAI), health assessment questionnaire (HAQ)-disability index (DI), and matrix metalloproteinase-3 values were recorded at baseline and at 4, 8, and 12 months.ResultsThere was a significant difference in the percent changes of DAS28, CRP and CDAI at every time point versus baseline in both treatment groups. HAQ-DI was also significantly different at every time point in both groups except for at four months in the non-TNF group.ConclusionTofacitinib was well tolerated in active RA patients and exerted effects comparable to those of non-TNF biologics.
| S-EPMC6117139 | biostudies-literature
Project description:BackgroundThis multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of 7 biological disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib (TOF), one of the janus kinase inhibitors, in bDMARDs-naïve and bDMARDs-switched patients with rheumatoid arthritis (RA).MethodsThis study assessed 3897 patients and 4415 treatment courses with bDMARDs and TOF from 2001 to 2019 (2737 bDMARDs-naïve courses and 1678 bDMARDs-switched courses [59.5% of switched courses were their second agent], female 82.3%, baseline age 57.4 years, disease duration 8.5 years; rheumatoid factor positivity 78.4%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate 4.3; concomitant prednisolone [PSL] dose 6.1 mg/day [usage 42.4%], and methotrexate [MTX] dose 8.5 mg/week [usage 60.9%]). Treatment courses included abatacept (ABT; n = 663), adalimumab (ADA; n = 536), certolizumab pegol (CZP; n = 226), etanercept (ETN; n = 856), golimumab (GLM; n = 458), infliximab (IFX; n = 724), tocilizumab (TCZ; n = 851), and TOF (n = 101/only bDMARDs-switched cases). Drug discontinuation reasons (categorized into lack of effectiveness, toxic adverse events, non-toxic reasons, or remission) and rates were estimated at 36 months using Gray's test and statistically evaluated after adjusted by potential clinical confounders (age, sex, disease duration, concomitant PSL and MTX usage, starting date, and number of switched bDMARDs) using the Fine-Gray model.ResultsCumulative incidence of drug discontinuation for each reason was as follows: lack of effectiveness in the bDMARDs-naïve group (from 13.7% [ABT] to 26.9% [CZP]; P < 0.001 between agents) and the bDMARDs-switched group (from 18.9% [TCZ] to 46.1% [CZP]; P < 0.001 between agents); toxic adverse events in the bDMARDs-naïve group (from 4.6% [ABT] to 11.2% [ETN]; P < 0.001 between agents) and the bDMARDs-switched group (from 5.0% [ETN] to 15.7% [TOF]; P = 0.004 between agents); and remission in the bDMARDs-naïve group (from 2.9% [ETN] to 10.0% [IFX]; P < 0.001 between agents) and the bDMARDs-switched group (from 1.1% [CZP] to 3.3% [GLM]; P = 0.9 between agents).ConclusionsRemarkable differences were observed in drug retention of 7 bDMARDs and TOF between bDMARDs-naïve and bDMARDs-switched cases.
| S-EPMC7296929 | biostudies-literature
Project description: Not available
| S-EPMC6469573 | biostudies-literature
Project description:ObjectivesTo evaluate the risk of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with tofacitinib.MethodsPhase II, III and long-term extension clinical trial data (April 2013 data-cut) from the tofacitinib RA programme were reviewed. OIs defined a priori included mycobacterial and fungal infections, multidermatomal herpes zoster and other viral infections associated with immunosuppression. For OIs, we calculated crude incidence rates (IRs; per 100 patient-years (95% CI)); for tuberculosis (TB) specifically, we calculated rates stratified by patient enrolment region according to background TB IR (per 100 patient-years): low (≤0.01), medium (>0.01 to ≤0.05) and high (>0.05).ResultsWe identified 60 OIs among 5671 subjects; all occurred among tofacitinib-treated patients. TB (crude IR 0.21, 95% CI of (0.14 to 0.30)) was the most common OI (n=26); median time between drug start and diagnosis was 64 weeks (range 15-161 weeks). Twenty-one cases (81%) occurred in countries with high background TB IR, and the rate varied with regional background TB IR: low 0.02 (0.003 to 0.15), medium 0.08 (0.03 to 0.21) and high 0.75 (0.49 to 1.15). In Phase III studies, 263 patients diagnosed with latent TB infection were treated with isoniazid and tofacitinib concurrently; none developed TB. For OIs other than TB, 34 events were reported (crude IR 0.25 (95% CI 0.18 to 0.36)).ConclusionsWithin the global tofacitinib RA development programme, TB was the most common OI reported but was rare in regions of low and medium TB incidence. Patients who screen positive for latent TB can be treated with isoniazid during tofacitinib therapy.
| S-EPMC4893093 | biostudies-literature
Project description:BackgroundWe sought to compare the benefits and safety of 6 biologics (abatacept, adalimumab, anakinra, etanercept, infliximab and rituximab) in patients with rheumatoid arthritis.MethodsIn this network meta-analysis, we included all completed and updated Cochrane reviews on biologics for rheumatoid arthritis. We included data from all placebo-controlled trials that used standard dosing regimens. The major outcomes were benefit (defined as a 50% improvement in patient- and physician-reported criteria of the American College of Rheumatology [ACR50]) and safety (determined by the number of withdrawals related to adverse events). We used mixed-effects logistic regression to carry out an indirect comparison of the treatment effects between biologics.ResultsCompared with placebo, biologics were associated with a clinically important higher ACR50 rate (odds ratio [OR] 3.35, 95% confidence interval [CI] 2.62-4.29) and a number needed to treat for benefit of 4 (95% CI 4-6). However, biologics were associated with more withdrawals related to adverse events (OR 1.39, 95% CI 1.13-1.71), with a number needed to treat for harm of 52 (95% CI 29-152). Anakinra was less effective than all of the other biologics, although this difference was statistically significant only for the comparison with adalimumab (OR 0.45, 95% CI 0.21-0.99) and etanercept (OR 0.34, 95% CI 0.14-0.81). Adalimumab, anakinra and infliximab were more likely than etanercept to lead to withdrawals related to adverse events (adalimumab OR 1.89, 95% CI 1.18-3.04; anakinra OR 2.05, 95% CI 1.27-3.29; and infliximab OR 2.70, 95% CI 1.43-5.26).InterpretationGiven the limitations of indirect comparisons, anakinra was less effective than adalimumab and etanercept, and etanercept was safer than adalimumab, anakinra and infliximab. This summary of the evidence will help physicians and patients to make evidence-based choices about biologics for the treatment of rheumatoid arthritis.
| S-EPMC2780484 | biostudies-literature
Project description:IntroductionPeficitinib, a Janus kinase (JAK) inhibitor, is approved for clinical use in Japan, Korea, and Taiwan, but head-to-head comparisons versus other JAK inhibitors are lacking. We indirectly compared peficitinib, tofacitinib, and baricitinib for rheumatoid arthritis treatment.MethodsWe searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and congress archives up until February 12, 2019, for randomized controlled trials of peficitinib, tofacitinib, and baricitinib. Efficacy (American College of Rheumatology responses, disease activity scores, modified total Sharp score, Simplified Disease Activity Index [SDAI]) and safety outcomes were compared using a Bayesian network meta-analysis. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results. A network meta-regression assessed the impact on outcomes of proportions of patients receiving concomitant methotrexate or of Asian ethnicity.ResultsThe network meta-analysis included 21 randomized controlled trials. At 12 weeks, all evaluable efficacy outcomes were comparable or improved with peficitinib 150 mg and 100 mg once daily, versus baricitinib 2 and 4 mg once daily and tofacitinib 5 mg twice daily. At 24 weeks, efficacy outcomes were comparable or improved for each peficitinib dose versus baricitinib and tofacitinib. Risk of adverse events and serious adverse events at 12 weeks were similar with peficitinib 100 and 150 mg versus baricitinib and tofacitinib. The proportion of patients receiving concomitant methotrexate had no effect on any outcome analyzed, but Asian ethnicity had a positive effect on multiple efficacy outcomes.ConclusionsPeficitinib had comparable efficacy versus tofacitinib and baricitinib for reduction in disease activity as measured by SDAI, and for reduction in progression of joint damage as measured radiographically. No notable differences in safety outcomes were observed. Further studies are required to better characterize the impact of ethnicity on the efficacy of JAK inhibitors.
| S-EPMC8217393 | biostudies-literature