Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis: A network meta-analysis.
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SUBMITTER: Hazlewood GS
PROVIDER: S-EPMC7087436 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo compare methotrexate based disease modifying antirheumatic drug (DMARD) treatments for rheumatoid arthritis in patients naive to or with an inadequate response to methotrexate.DesignSystematic review and Bayesian random effects network meta-analysis of trials assessing methotrexate used alone or in combination with other conventional synthetic DMARDs, biologic drugs, or tofacitinib in adult patients with rheumatoid arthritis.Data sourcesTrials were identified from Medline, Embase, and Central databases from inception to 19 January 2016; abstracts from two major rheumatology meetings from 2009 to 2015; two trial registers; and hand searches of Cochrane reviews.Study selection criteriaRandomized or quasi-randomized trials that compared methotrexate with any other DMARD or combination of DMARDs and contributed to the network of evidence between the treatments of interest.Main outcomesAmerican College of Rheumatology (ACR) 50 response (major clinical improvement), radiographic progression, and withdrawals due to adverse events. A comparison between two treatments was considered statistically significant if its credible interval excluded the null effect, indicating >97.5% probability that one treatment was superior.Results158 trials were included, with between 10 and 53 trials available for each outcome. In methotrexate naive patients, several treatments were statistically superior to oral methotrexate for ACR50 response: sulfasalazine and hydroxychloroquine ("triple therapy"), several biologics (abatacept, adalimumab, etanercept, infliximab, rituximab, tocilizumab), and tofacitinib. The estimated probability of ACR50 response was similar between these treatments (range 56-67%), compared with 41% with methotrexate. Methotrexate combined with adalimumab, etanercept, certolizumab, or infliximab was statistically superior to oral methotrexate for inhibiting radiographic progression, but the estimated mean change over one year with all treatments was less than the minimal clinically important difference of 5 units on the Sharp-van der Heijde scale. Triple therapy had statistically fewer withdrawals due to adverse events than methotrexate plus infliximab. After an inadequate response to methotrexate, several treatments were statistically superior to oral methotrexate for ACR50 response: triple therapy, methotrexate plus hydroxychloroquine, methotrexate plus leflunomide, methotrexate plus intramuscular gold, methotrexate plus most biologics, and methotrexate plus tofacitinib. The probability of response was 61% with triple therapy and ranged widely (27-70%) with other treatments. No treatment was statistically superior to oral methotrexate for inhibiting radiographic progression. Methotrexate plus abatacept had a statistically lower rate of withdrawals due to adverse events than several treatments.ConclusionsTriple therapy (methotrexate plus sulfasalazine plus hydroxychloroquine) and most regimens combining biologic DMARDs with methotrexate were effective in controlling disease activity, and all were generally well tolerated in both methotrexate naive and methotrexate exposed patients.
| S-EPMC4849170 | biostudies-literature
Project description:Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX.
| S-EPMC3841743 | biostudies-literature
Project description:ObjectiveTo assess the efficacy and safety of upadacitinib (UPA), an oral Janus kinase inhibitor, as monotherapy or in combination with non-biologic DMARDs (nbDMARDs) in patients with PsA.MethodsPooled data were analysed from patients with prior inadequate response or intolerance to one or more nbDMARD (SELECT-PsA 1) or one or more biologic DMARD (SELECT-PsA 2) who received placebo, UPA 15 mg once daily (QD) or UPA 30 mg QD as monotherapy or in combination with two or fewer nbDMARDs for 24 weeks. Efficacy outcomes included achievement of ACR responses, Psoriasis Area and Severity Index responses, minimal disease activity and change from baseline and clinically meaningful improvement in the HAQ Disability Index. Adverse events (AEs) were summarized.ResultsA total of 1916 patients were included; 574 (30%) received monotherapy and 1342 (70%) received combination therapy. Placebo-subtracted treatment effects for a 20% improvement in ACR criteria at week 12 were 33.7% (95% CI 24.4, 43.1) and 34.0% (95% CI 27.9, 40.1) for UPA 15 mg QD monotherapy and combination therapy, respectively, and 45.7% (95% CI 36.9, 54.5) and 39.6% (95% CI 33.7, 45.5) for UPA 30 mg QD monotherapy and combination therapy, respectively. Treatment effects for other outcomes were consistent between monotherapy and combination therapy. AE frequency was generally similar for UPA monotherapy and combination therapy, although hepatic disorders and creatine phosphokinase elevation were more common with combination therapy vs monotherapy.ConclusionThe efficacy and safety of UPA were generally consistent when administered as monotherapy or in combination with nbDMARDs through 24 weeks, supporting the use of UPA with or without nbDMARDs in PsA.Trial registrationClinicalTrials.gov (https://clinicaltrials.gov): SELECT-PsA 1 (NCT03104400), SELECT-PsA 2 (NCT03104374).
| S-EPMC9348611 | biostudies-literature
Project description: Not available
| S-EPMC6469573 | biostudies-literature
Project description:The aim of this study was to compare the response between subsequent use of anti-tumor necrosis factor ? (anti-TNF) agents and biologic disease-modifying anti-rheumatic drugs (bDMARD) with other mechanism of action (MOA) in rheumatoid arthritis (RA) patients with history of anti-TNF treatment as their first bDMARD.A retrospective chart review was conducted at eight community-based rheumatology practices in the United States in 2012. Routine Assessment of Patient Index Data 3 (RAPID3) response was measured by comparing baseline and 6-month scores. Poor response was defined as decrease <1.8 points, follow-up score >12, or treatment discontinuation before 6 months. Percentages of patients with good and good or moderate RAPID3 response were compared for second and third biologics. Multivariate models controlled for potential confounders.Of 176 patients whose charts were abstracted, 122 (69.3%) received another anti-TNF agent after they discontinued their first anti-TNF. RAPID3 scores were available for 160 patients. A patient receiving a second bDMARD with another MOA had a higher good or moderate response than a patient receiving anti-TNF (53.5 vs. 30.7%, p = 0.01). In the multivariate models, treatment with another MOA was more likely to produce a good RAPID3 response [odds ratio (OR), 2.42; 95% confidence interval (CI), 1.05-5.58] or a good or moderate response (OR, 2.21; 95% CI, 1.23-3.97) than treatment with an anti-TNF.In patients who have discontinued anti-TNF agents as their first bDMARD, RAPID3 response rates are better for those receiving agents with a different MOA rather than another anti-TNF. Physicians should consider using a bDMARD with a different MOA as the next bDMARD for RA patients whose anti-TNF agent has failed.
| S-EPMC4883258 | biostudies-other
Project description: Not available
| S-EPMC7068903 | biostudies-literature
Project description:There has been some debate between biologic disease modifying anti-rheumatic drugs (bDMARDs) treatment and hypertension (HTN) in rheumatoid arthritis (RA). The aim of this study was to determine the effect of bDMARDs on the development of HTN in patients with RA.A total of 996 patients eligible for analysis were recruited from the Korean College of Rheumatology Biologics & Targeted Therapy (KOBIO) registry from 2012 to 2018. The bDMARDs were tumor necrosis factor (TNF) inhibitors, abatacept, and tocilizumab. The cDMARDs included methotrexate, hydroxychloroquine, and leflunomide. The incidence rate and 95% confidence interval of HTN were estimated using the Kaplan-Meier method. Hazard ratio (HR) of risk factors associated with hypertension was assessed by cox proportional hazard model analysis.Among the 996 patients, 62 patients (6.2%) were newly diagnosed with HTN. There were differences in incidence rate of HTN among conventional DMARDs (cDMARDs), TNF inhibitors, tocilizumab, and abatacept during the follow-up period (P = .015). Kaplan-Meier analysis showed that there was a significant difference in incident HTN only between cDMARDs and tocilizumab (P = .001). Systolic blood pressure and positive rheumatoid factor were associated with development of HTN (HR = 1.049, P = .016 and HR = 1.386, P = .010, respectively). Cox proportional hazard model analysis showed no difference in the development of HTN between bDMARDs and cDMARDs in RA.This study showed that bDMARDs treatment might not increase risk of incident HTN in patients with RA, compared to cDMARDs.
| S-EPMC7478791 | biostudies-literature
Project description:Biologics, possibly in combination with a conventional disease-modifying antirheumatic drug (DMARD) - preferably methotrexate (MTX), are used in accordance with the recommendations of the international rheumatological societies. However, in clinical practice, this recommendation is often problematic, as many rheumatologists know from personal experience. The quality of life of the patient is affected mainly by drug-induced intolerances (eg, MTX). Thus, the acceptance of the patient to treatment is often so inadequate that a discontinuation of the drug is necessary. In daily practice, approximately 30% of patients with biological therapy receive no concomitant DMARD according to the register data.
| S-EPMC4440355 | biostudies-literature
Project description:IntroductionThis study examined the use of anti-tumor necrosis factor (anti-TNF) monotherapy, adherence with non-biologic disease-modifying anti-rheumatic drugs (nbDMARDs) in patients receiving a combination of anti-TNF therapies and nbDMARDs, and the impact of nbDMARD adherence on anti-TNF persistence among patients with rheumatoid arthritis (RA).MethodsPatients with RA (aged ≥18 years) from a US commercial health plan with claims for anti-TNFs (2006-2010) were defined as either biologic-naive or -exposed anti-TNF initiators based on previous nbDMARD use. Adherence to nbDMARDs and anti-TNF persistence were estimated. Cox regression estimated the association between nbDMARD adherence and anti-TNF persistence.ResultsAmong 9764 patients identified (mean age 50.2 years; 78% female), 55% of biologic-naive patients and 49% of previously exposed patients initiated any combination therapy during follow-up. Among biologic-naive combination therapy patients, 53% adhered to nbDMARD therapy <80% of the time while receiving anti-TNF therapies; 33% had <60% adherence. Compared with the most adherent patients, patients adherent to nbDMARDs 20% to 79% of the time were 30% to 20% more likely to discontinue their anti-TNF therapy in the period >90 days after starting the anti-TNF therapy. This relationship was not observed for patients with nbDMARD adherence of <20% (who were less likely to discontinue their anti-TNF therapy during the first 90 days of treatment).ConclusionAlmost one-third of patients with RA receiving anti-TNF therapy received it as pure monotherapy. About one-third of combination therapy recipients had <60% adherence to nbDMARDs. Higher nbDMARD adherence may be associated with better anti-TNF persistence after an initial treatment period.
| S-EPMC4883262 | biostudies-literature
Project description:The aim of this study was to evaluate the cost-effectiveness of Anbainuo (ABN) plus methotrexate (MTX) (ABN + MTX) versus conventional disease-modifying anti-rheumatic drugs (cDMARDs) in rheumatoid arthritis (RA) patients.Forty-eight moderate to severe RA patients underwent ABN + MTX or cDMARDs treatment were consecutively enrolled and assigned to ABN + MTX group (n = 26) and control group (n = 22). Patients were followed up and their disease activity and quality of life (QoL) were evaluated at 3rd month, 6th month and 12th month after initiation of treatment. Treatment costs of 2 groups were calculated, then pharmacoeconomic analysis was performed.ABN + MTX increased drug cost and total cost while decreased indirect cost compared with cDMARDs after 12-month treatment. ABN + MTX group gained additional 0.22 quality-adjusted life years (QALY) and yielded an incremental cost-effectiveness ratio (ICER) of ¥104,293.6 per QALY after treatment. Sensitivity analysis reveals that rising ABN price by 20% produced an ICER of ¥130,403.6 per QALY, which was still lower than 3 times of the mean gross domestic product (GDP) per capita during the same period in China (¥165,960). Besides, ABN + MTX was more cost-effective in severe RA patients compared to moderate RA patients.ABN + MTX is cost-effective in treating moderate to severe RA patients compared with cDMARDs, although the total cost of ABN + MTX is relatively higher.
| S-EPMC6890288 | biostudies-literature