Dataset Information

Methotrexate (MTX) Plus Hydroxychloroquine versus MTX Plus Leflunomide in Patients with MTX-Resistant Active Rheumatoid Arthritis: A 2-Year Cohort Study in Real World.

ABSTRACT:

Purpose

To compare the efficacy, safety, and cost-effectiveness of methotrexate (MTX) plus hydroxychloroquine (HCQ) vs MTX plus leflunomide (LEF) in established rheumatoid arthritis (RA) with inadequate response to MTX monotherapy in a real-world Chinese cohort.

Patients and methods

A prospective RA cohort (n=549) was screened with eligible patients who had inadequate response (disease activity score in 28 joints using erythrocyte sedimentation rate, DAS28-ESR>3.2) to initial MTX monotherapy and subsequently received either MTX+HCQ or MTX+LEF. Propensity score matching (PSM) was applied to adjust the possible baseline confounders between two groups. The primary outcome was the proportion of patients achieving first remission (DAS28-ESR<2.6) during follow-up by log rank test. Secondary outcomes were changes of DAS28, glucocorticoids (GCs) exposure, safety, cost-effectiveness, sustained remission, and low disease activity (LDA) rate after 24-month follow-up.

Results

Overall, 222 eligible patients were subjected to the aforementioned two treatment protocols (MTX+HCQ, n=102; MTX+LEF, n=120). After PSM adjustment, 97 patients in each group were analyzed. A higher remission rate was observed in the MTX+HCQ group than in the MTX+LEF group (70.1% vs 56.7%, P=0.048). The median time to remission was 11 and 16 months in the two groups, respectively. At the endpoint, more patients achieved remission (46.8% vs 32.5%, P=0.063) and maintained sustained LDA in the HCQ group (53.2% vs 38.6%, P=0.062) and also more patients withdrew GCs in this group (32% vs 16.7%, P=0.053) than those in the LEF group. Safety profiles were non-alarming, with no significant difference between the two groups. The incremental cost-effectiveness ratio yielded by MTX+HCQ over MTX+LEF was $1,111.8 per quality-adjusted life-year (QALY), within the cost-effective threshold set as the per capita gross domestic product (GDP) of China.

Conclusion

The MTX+HCQ combination was seemingly superior to MTX+LEF in a real-world cohort of Chinese RA patients with inadequate response to methotrexate monotherapy in respect of the efficacy and cost-effectiveness.

SUBMITTER: Zhang L

PROVIDER: S-EPMC7755368 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Methotrexate (MTX) Plus Hydroxychloroquine versus MTX Plus Leflunomide in Patients with MTX-Resistant Active Rheumatoid Arthritis: A 2-Year Cohort Study in Real World.

Zhang Le L Chen Fangfang F Geng Shikai S Wang Xiaodong X Gu Liyang L Lang Yitian Y Li Ting T Ye Shuang S

Journal of inflammation research 20201218

<h4>Purpose</h4>To compare the efficacy, safety, and cost-effectiveness of methotrexate (MTX) plus hydroxychloroquine (HCQ) vs MTX plus leflunomide (LEF) in established rheumatoid arthritis (RA) with inadequate response to MTX monotherapy in a real-world Chinese cohort.<h4>Patients and methods</h4>A prospective RA cohort (n=549) was screened with eligible patients who had inadequate response (disease activity score in 28 joints using erythrocyte sedimentation rate, DAS28-ESR>3.2) to initial MTX ...[more]

PMID: 33376379

Similar Datasets

Project description:Objective:To assess methotrexate (MTX) adherence using the Medication Event Monitoring System (MEMS) and characterize associations with adherence in patients with rheumatoid arthritis (RA). Methods:Eligible patients participated in Forward, the National Databank for Rheumatic Diseases, and recently (12 months or sooner) initiated oral MTX. MEMS was used to compile MTX weekly dosing over 24 weeks. The Beliefs about Medicines Questionnaire (BMQ) was completed, and baseline demographics and disease characteristics obtained. MTX adherence (percentage of weeks dose taken correctly), implementation (percentage of weeks dose taken correctly from initiation until last dose), and persistence (duration from initiation to last dose) were calculated. Analyses measured associations between patient characteristics and adherence, modeled using logistic generalized estimating equations and censored Poisson regression, and persistence modeled using Cox regression. Results:Overall, 60 of 119 eligible patients were included in the analysis. MTX adherence, implementation, and persistence were 75%, 80%, and 83%, respectively, at 24 weeks. Demographics and disease characteristics were generally similar between patients with 1 week or less and 2 weeks or more of missed MTX. Unemployment, less disability, higher Patient Global scores, and no prior disease-modifying antirheumatic drug (DMARD) use were associated with correct dosing. No significant differences in adherence were observed between patients receiving concomitant MTX versus MTX monotherapy, and biologic DMARD-experienced versus biologic DMARD-naïve patients. Higher scores in BMQ Specific Necessity (indicating a greater belief in the necessity of the medication) was associated with a decreased likelihood of dosing at an interval shorter than prescribed (odds ratio 0.89). Conclusion:Even in a participatory group over a short period, MTX adherence was suboptimal and associated with certain demographics, medication experience, and beliefs about medicines. This suggests a need for screening and alternative treatment opportunities in nonadherent MTX patients with RA.

Project description:IntroductionThe treatment of rheumatoid arthritis (RA) patients with anti-tumor necrosis factor alpha (TNF?) biological drugs has dramatically improved the prognosis of these patients. However, a third of the treated patients do not respond to this therapy. Thus, the search for biomarkers of clinical response to these agents is currently highly active. Our aim is to analyze the number and distribution of circulating monocytes, and of their CD14?highCD16?, CD14?highCD16? and CD14?lowCD16+ subsets in methotrexate (MTX) non-responder patients with RA, and to determine their value in predicting the clinical response to adalimumab plus MTX treatment.MethodsThis prospective work investigated the number of circulating monocytes, and of their CD14?highCD16?, CD14?highCD16? and CD14?lowCD16? subsets, in 35 MTX non-responder patients with RA before and after three and six months of anti-TNF? treatment using multiparametric flow cytometry. The number of circulating monocytes in an age- and sex-matched healthy population was monitored as a control.ResultsNon-responder patients with RA show an increased number of monocytes and of their CD14?highCD16?, CD14?highCD16? and CD14?lowCD16? subsets after three months of adalimumab plus MTX treatment that remained significantly increased at six months. In contrast, significant normalization of the numbers of circulating monocytes was found in responders at three months of adalimumab plus MTX treatment that lasts up to six months. CX3CR1 expression is increased in monocytes in non-responders. At three months of anti-TNF? treatment the number of circulating monocytes and their subsets was associated with at least 80% sensitivity, 84% specificity and an 86% positive predictive value (PPV) in terms of discriminating between eventual early responders and non-responders.ConclusionsThe absolute number of circulating monocytes and of their CD14?highCD16?, CD14?highCD16? and CD14?lowCD16? subsets at three months of adalimumab plus MTX treatment, have a predictive value (with high specificity and sensitivity) in terms of the clinical response after six months of anti-TNF? treatment in patients with RA.

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.

Project description:As patients with rheumatoid arthritis (RA) receive treatment with anti-tumour necrosis factors over several years, it is important to evaluate their long-term safety and efficacy. The objective of this study was to examine the safety and benefits of certolizumab pegol (CZP)+methotrexate (MTX) treatment for almost 5 years in patients with RA.Patients who completed the 24-week Rheumatoid Arthritis Prevention of Structural Damage (RAPID) 2 randomized controlled trial (RCT; NCT00160602), or who were American College of Rheumatology (ACR) 20 non-responders at Week 16, entered the open-label extension (OLE; NCT00160641). After ?6 months treatment with CZP 400 mg every two weeks (Q2W), dose was reduced to 200 mg Q2W, the approved maintenance dose. Safety data are presented from all patients who received ?1 dose CZP (Safety population, n=612). Efficacy data are presented to Week 232 for the intent-to-treat (ITT, n=492) and Week 24 CZP RCT Completer (n=342) populations, and through 192 weeks of dose-reduction for the Dose-reduction population (patients whose CZP dose was reduced to 200 mg, n=369). Radiographic progression (modified total Sharp score change from RCT baseline >0.5) to Week 128 is reported for the Week 24 CZP Completers.In the RCT, 619 patients were randomized to CZP+MTX (n=492) or placebo+MTX (n=127). Overall, 567 patients (91.6%) entered the OLE: 447 CZP and 120 placebo patients. Of all randomized patients, 358 (57.8%) were ongoing at Week 232. Annual drop-out rates during the first four years ranged from 8.4-15.0%. Event rates per 100 patient-years were 163.0 for adverse events (AEs) and 15.7 for serious AEs. Nineteen patients (3.1%) had fatal AEs (incidence rate=0.8). Clinical improvements in the RCT were maintained to Week 232 in the CZP Completers: mean Disease Activity Score 28 (Erythrocyte Sedimentation Rate) change from baseline was -3.4 and ACR20/50/70 responses 68.4%/47.1%/25.1% (non-responder imputation). Similar improvements observed in the ITT were maintained following dose-reduction. 73.2% of CZP Completers had no radiographic progression at Week 128.In patients with active RA despite MTX therapy, CZP was well tolerated, with no new safety signals identified. CZP provided sustained improvements in clinical outcomes for almost 5 years.ClinicalTrials.gov, NCT00160602 and NCT00160641 . Registered 8 September 2005.

Dataset Information

Methotrexate (MTX) Plus Hydroxychloroquine versus MTX Plus Leflunomide in Patients with MTX-Resistant Active Rheumatoid Arthritis: A 2-Year Cohort Study in Real World.

Purpose

Patients and methods

Results

Conclusion

Publications

Methotrexate (MTX) Plus Hydroxychloroquine versus MTX Plus Leflunomide in Patients with MTX-Resistant Active Rheumatoid Arthritis: A 2-Year Cohort Study in Real World.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure