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Comparative Effectiveness of Tumor Necrosis Factor Agents and Disease-modifying Antirheumatic Therapy in Children with Enthesitis-related Arthritis: The First Year after Diagnosis.

ABSTRACT: To characterize the effect of anti-tumor necrosis factor (TNF) therapy compared to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in children with enthesitis-related arthritis (ERA) over the first year after diagnosis.We conducted a multicenter retrospective comparative effectiveness study of children diagnosed with ERA. We estimated the effect of anti-TNF therapy on clinical variables (active joint count, tender entheses count) and patient-reported pain and global assessment of disease activity over the first year after diagnosis using state-of-the-art comparative effectiveness analytic methods.During the study period, 217 patients newly diagnosed with ERA had a total of 965 clinic visits the first year after disease diagnosis. Children [median age 11.6 yrs, interquartile range 10-14] were treated with anti-TNF monotherapy (n = 33, 15.2%), csDMARD monotherapy (n = 73, 33.6%), or both (n = 52, 23.9%) in the first year after disease diagnosis. There was a statistically significant improvement in the primary outcome, active joint count, over time in children who received an anti-TNF drug versus those who did not (p = 0.03). Additionally, use of anti-TNF therapy versus no anti-TNF therapy was associated with less patient-reported pain (p < 0.01) and improved disease activity over time as assessed by the clinical Juvenile Arthritis Disease Activity Score (p < 0.01). The magnitude of estimated effect on clinical outcomes was uniformly greater, with the exception of tender entheses count, in children treated with an anti-TNF drug versus a csDMARD.During the first year after diagnosis, anti-TNF exposure was associated with benefits for several clinically meaningful outcomes in children with enthesitis-related arthritis.

SUBMITTER: Weiss PF

PROVIDER: S-EPMC5750113 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Comparative Effectiveness of Tumor Necrosis Factor Agents and Disease-modifying Antirheumatic Therapy in Children with Enthesitis-related Arthritis: The First Year after Diagnosis.

Weiss Pamela F PF Xiao Rui R Brandon Timothy G TG Pagnini Ilaria I Wright Tracey B TB Beukelman Timothy T Morgan-DeWitt Esi E Feudtner Chris C

The Journal of rheumatology 20170915 1

<h4>Objective</h4>To characterize the effect of anti-tumor necrosis factor (TNF) therapy compared to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in children with enthesitis-related arthritis (ERA) over the first year after diagnosis.<h4>Methods</h4>We conducted a multicenter retrospective comparative effectiveness study of children diagnosed with ERA. We estimated the effect of anti-TNF therapy on clinical variables (active joint count, tender entheses count) and patie ...[more]

PMID: 28916542

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Project description:Background & aimsInhibitors of tumor necrosis factor (anti-TNF agents) are the most effective therapy for Crohn's disease (CD). We evaluated the real-world comparative effectiveness and safety of different anti-TNF agents (infliximab, adalimumab, and certolizumab pegol) in biologic-naive patients with CD in a retrospective, propensity-matched cohort study using a national administrative claims database (Optum Labs Data Warehouse).MethodsWe identified 3205 biologic-naive patients with CD (mean age, 41 ± 15 years; 45% male; median follow-up period after anti-TNF therapy, 19 months; 44.5% on infliximab and 38.9% on adalimumab) who received their first prescription for an anti-TNF agent (infliximab, adalimumab, or certolizumab pegol) after a 12-month period without any anti-TNF treatment (baseline), and with a minimum follow-up period of 6 months after their initial anti-TNF prescription, between 2006 and 2014. The primary outcomes were all-cause and CD-related hospitalization, abdominal surgery, corticosteroid use, and serious infections. We performed a propensity-matched, Cox proportional hazards analysis, accounting for baseline demographics, health care use, comorbidities, and use of CD-related medication.ResultsCompared with adalimumab-treated patients, infliximab-treated patients had a lower risk of CD-related hospitalization (adjusted hazard ratio [aHR], 0.80; 95% confidence interval [CI], 0.66-0.98), abdominal surgery (aHR, 0.76; 95% CI, 0.58-0.99), and corticosteroid use (aHR, 0.85; 95% CI, 0.75-0.96). Compared with certolizumab pegol-treated patients, infliximab-treated patients had a lower risk of all-cause hospitalization (aHR, 0.70; 95% CI, 0.52-0.95) and CD-related hospitalization (aHR, 0.59; 95% CI, 0.39-0.90). Adalimumab-treated patients had outcomes comparable with those of certolizumab pegol-treated patients. All agents had comparable risk of serious infections.ConclusionsIn a retrospective analysis of a large cohort of biologic-naive patients with CD, we found infliximab to be superior to adalimumab and certolizumab pegol for patient-relevant outcomes, without increased risk of serious infections.

Project description:ImportanceCytokine signaling, including tumor necrosis factor (TNF) and interleukin (IL)-6, through the Janus-kinase (JAK)-signal transducer and activator of transcription pathway, was hypothesized to attenuate the risk of Alzheimer disease and related dementia (ADRD) in the Drug Repurposing for Effective Alzheimer Medicines (DREAM) initiative based on multiomics phenotyping.ObjectiveTo evaluate the association between treatment with tofacitinib, tocilizumab, or TNF inhibitors compared with abatacept and risk of incident ADRD.Design, setting, and participantsThis cohort study was conducted among US Medicare fee-for-service patients with rheumatoid arthritis aged 65 years and older from 2007 to 2017. Patients were categorized into 3 cohorts based on initiation of tofacitinib (a JAK inhibitor), tocilizumab (an IL-6 inhibitor), or TNF inhibitors compared with a common comparator abatacept (a T-cell activation inhibitor). Analyses were conducted from August 2020 to August 2021.Main outcomes and measuresThe main outcome was onset of ADRD based on diagnosis codes evaluated in 4 alternative analysis schemes: (1) an as-treated follow-up approach, (2) an as-started follow-up approach incorporating a 6-month induction period, (3) incorporating a 6-month symptom to diagnosis period to account for misclassification of ADRD onset, and (4) identifying ADRD through symptomatic prescriptions and diagnosis codes. Hazard ratios (HRs) with 95% CIs were calculated from Cox proportional hazard regression after adjustment for 79 preexposure characteristics through propensity score matching.ResultsAfter 1:1 propensity score matching to patients using abatacept, a total of 22 569 propensity score-matched patient pairs, including 4224 tofacitinib pairs (mean [SD] age 72.19 [5.65] years; 6945 [82.2%] women), 6369 tocilizumab pairs (mean [SD] age 72.01 [5.46] years; 10 105 [79.4%] women), and 11 976 TNF inhibitor pairs (mean [SD] age 72.67 [5.91] years; 19 710 [82.3%] women), were assessed. Incidence rates of ADRD varied from 2 to 18 per 1000 person-years across analyses schemes. There were no statistically significant associations of ADRD with tofacitinib (analysis 1: HR, 0.90 [95% CI, 0.55-1.51]; analysis 2: HR, 0.78 [95% CI, 0.53-1.13]; analysis 3: HR, 1.29 [95% CI, 0.72-2.33]; analysis 4: HR, 0.50 [95% CI, 0.21-1.20]), tocilizumab (analysis 1: HR, 0.82 [95% CI, 0.55-1.21]; analysis 2: HR, 1.05 [95% CI, 0.81-1.35]; analysis 3: HR, 1.21 [95% CI, 0.75-1.96]; analysis 4: HR, 0.78 [95% CI, 0.44-1.39]), or TNF inhibitors (analysis 1: HR, 0.93 [95% CI, 0.72-1.20]; analysis 2: HR, 1.02 [95% CI, 0.86-1.20]; analysis 3: HR, 1.13 [95% CI, 0.86-1.48]; analysis 4: 0.90 [95% CI, 0.60-1.37]) compared with abatacept. Results from prespecified subgroup analysis by age, sex, and baseline cardiovascular disease were consistent except in patients with cardiovascular disease, for whom there was a potentially lower risk of ADRD with TNF inhibitors vs abatacept, but only in analyses 2 and 4 (analysis 1: HR, 0.76 [95% CI, 0.50-1.16]; analysis 2: HR, 0.74 [95% CI, 0.56-0.99]; analysis 3: HR, 1.03 [95% CI, 0.65-1.61]; analysis 4: HR, 0.45 [95% CI, 0.21-0.98]).Conclusions and relevanceThis cohort study did not find any association of risk of ADRD in patients treated with tofacitinib, tocilizumab, or TNF inhibitors compared with abatacept.

Project description:BackgroundAnti-tumor necrosis factor (anti-TNF) agents are an effective, but costly, treatment for spondyloarthritis (SpA). Worldwide, multiple sets of access criteria aim to restrict anti-TNF therapy to patients with specific clinical characteristics, yet the influence of access criteria on anti-TNF cost-effectiveness is unknown. Our objective was to use data from the DESIR cohort, a prospective study of early SpA patients in France, to determine whether the French anti-TNF access criteria are the most cost-effective in that setting relative to other potential restrictions.MethodsWe used data from the DESIR cohort to create five study populations of patients meeting anti-TNF access criteria from Canada, France, Germany, United Kingdom, and Hong Kong, respectively. For each study population, we calculated the costs and quality-adjusted life years (QALYs) over 1 year of patients treated and not treated with anti-TNF therapy. To control for differences between anti-TNF users and non-users, we used linear regression models to derive adjusted mean costs and QALYs. We calculated incremental cost-effectiveness ratios (ICERs) representing the incremental cost per additional QALY gained by treating with an anti-TNF within each of the five study populations, using bootstrapping to explore the range of uncertainty in costs and QALYs. A series of sensitivity analyses was conducted, including one to simulate the effect of a 24-week stopping rule for anti-TNF non-responders.ResultsAnti-TNF access criteria from France were satisfied by the largest proportion of DESIR patients (27.8%), followed by Germany (25.1%), Canada (23.8%), the UK (12.1%) and Hong Kong (8.6%). Confidence intervals around incremental costs and QALYs in the basecase analysis were overlapping, indicating that anti-TNF cost-effectiveness estimates derived from each subset were similar. In the sensitivity analysis that examined the effect of excluding costs accumulated past 24 weeks by anti-TNF non-responders, the incremental cost per QALY was reduced by approximately 25% relative to the basecase analysis (France: €857,992 vs. €1,105,859; Canada: € 626,459 vs. €818,186; Germany: € 422,568 vs. €545,808); UK €578,899 vs. €766,217; Hong Kong €335,418 vs. €456,850).ConclusionsAnti-TNF cost-effectiveness is strongly affected by treatment continuation among non-responders. Access criteria could improve anti-TNF cost-effectiveness by defining patients likely to respond.

Project description:IntroductionControlled clinical studies have shown that the efficacy of tocilizumab (TCZ) monotherapy is superior to that of tumor necrosis factor inhibitor (TNFi) monotherapy and comparable to that of TCZ plus methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). This study compared the real-world effectiveness of TCZ monotherapy vs. TNFis plus MTX in US patients with RA.MethodsTCZ-naïve patients from the Corrona RA registry with prior exposure to ≥ 1 TNFi who initiated TCZ monotherapy or TNFi + MTX were included. Outcomes included mean change in Clinical Disease Activity Index (CDAI), achievement of low disease activity (LDA; CDAI ≤ 10), achievement of modified American College of Rheumatology (mACR) 20/50 responses, and mean change in modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients initiating TNFi + MTX were grouped by MTX dose (≤ 10 mg; > 10 to ≤ 15 mg; > 15 to ≤ 20 mg; > 20 mg); outcomes in each group were compared with TCZ monotherapy using trimmed populations (excluding patients outside the propensity score distribution overlap).ResultsPatients in all groups experienced improvement in CDAI at 6 months (mean change, - 6.9 to - 9.7), with no significant differences between the TCZ monotherapy and TNFi + MTX groups. Achievement of LDA and mACR responses at 6 months were comparable between the TCZ monotherapy and TNFi + MTX groups; overall, 26.8-38.0% of patients achieved LDA, 24.3-37.6% achieved mACR20 response and 13.2-20.8% achieved mACR50 response. The mean change in mHAQ at 6 months was - 0.1 in all groups.ConclusionsIn this real-world population of US patients with RA who had prior TNFi exposure, there was no evidence of a difference in the effectiveness of TCZ monotherapy compared with that of TNFi + MTX, regardless of MTX dose, at 6 months for improving RA disease activity.FundingCorrona, LLC. Plain language summary available for this article.

Dataset Information

Comparative Effectiveness of Tumor Necrosis Factor Agents and Disease-modifying Antirheumatic Therapy in Children with Enthesitis-related Arthritis: The First Year after Diagnosis.

Publications

Comparative Effectiveness of Tumor Necrosis Factor Agents and Disease-modifying Antirheumatic Therapy in Children with Enthesitis-related Arthritis: The First Year after Diagnosis.

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