Efficacy and safety of bucillamine, a d-penicillamine analogue, in patients with active rheumatoid arthritis

Japanese rheumatologists consider bucillamine (Buc) to be a useful disease-modifying antirheumatic drug (DMARD) and often give Buc to patients with rheumatoid arthritis (RA) prior to administering methotrexate (MTX). However, no large studies on the efficacy and safety of Buc in RA patients have been published in English to date. We therefore investigated the clinical course of RA patients treated with Buc and compared the results with those for patients treated with MTX to evaluate and confirm the place of Buc in therapeutic strategies for RA in Japan. Our results suggested that Buc should be given to patients with moderately active RA either before or after the administration of MTX because its efficacy can be judged within 3 months and because serious adverse events are rare. Issues like the ability of Buc to prevent joint destruction and its efficacy and safety when combined with agents like etanercept require future study.     

Efficacy profile of bucillamine in rheumatoid arthritis patients in a large observational cohort study,IORRA

Abstract

Bucillamine (Buc) is a disease-modifying antirheumatic drug (DMARD) developed in Japan, which has been used as one of the first-line DMARDs for the treatment of rheumatoid arthritis (RA) in Japan. However, direct comparison of this drug with standard DMARDs including sulfasalazine (SASP) and methotrexate (MTX) has been scarcely reported. We therefore tried to evaluate the clinical efficacy of Buc by analyzing the database from the long-term observational cohort study IORRA (previously known as J-ARAMIS). The cross-sectional analysis revealed that responses to Buc treatment were better in males, patients with shorter duration of illness, and those who were rheumatoid factor-negative. In the longitudinal analysis, although there was no marked difference among the baseline variables of patients with Buc, SASP, and MTX, the percentage of patients exhibiting moderate or good response to treatment, as rated using the European League Against Rheumatism improvement criteria, was higher in the Buc group (41.0%) than in the MTX (32.6%) and SASP groups (25.6%). These data support Buc as a candidate for being a first-line drug for the treatment of patients with RA.     

Efficacy profile of bucillamine in rheumatoid arthritis patients in a large observational cohort study, IORRA

Bucillamine (Buc) is a disease-modifying antirheumatic drug (DMARD) developed in Japan, which has been used as one of the first-line DMARDs for the treatment of rheumatoid arthritis (RA) in Japan. However, direct comparison of this drug with standard DMARDs including sulfasalazine (SASP) and methotrexate (MTX) has been scarcely reported. We therefore tried to evaluate the clinical efficacy of Buc by analyzing the database from the long-term observational cohort study IORRA (previously known as J-ARAMIS). The cross-sectional analysis revealed that responses to Buc treatment were better in males, patients with shorter duration of illness, and those who were rheumatoid factor-negative. In the longitudinal analysis, although there was no marked difference among the baseline variables of patients with Buc, SASP, and MTX, the percentage of patients exhibiting moderate or good response to treatment, as rated using the European League Against Rheumatism improvement criteria, was higher in the Buc group (41.0%) than in the MTX (32.6%) and SASP groups (25.6%). These data support Buc as a candidate for being a first-line drug for the treatment of patients with RA.     

A comparative study of the effects of bucillamine and salazosulfapyridine in the treatment of rheumatoid arthritis

Abstract

Bucillamine (Buc), developed in Japan, is a disease-modifying antirheumatic drug (DMARD) which has been used to treat numerous patients with rheumatoid arthritis (RA) in Japan and Korea with favorable results. However, it has not been used globally. In the present study, we compared the timing of onset of efficacy and the usefulness of this drug with that of the globally accepted agent salazosulfapyridine (SASP). There were 26 patients in the Buc group and 23 in the SASP group. We compared changes in the number of swollen joints, number of painful joints, duration of morning stiffness, grip strength, levels of inflammatory marker [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)], rheumatoid factor (RF), physician’s rating by visual analogue scale (VAS), patient’s rating of pain, patient’s overall rating (VAS), and improvement according to European League against Rheumatism (EULAR) criteria (DAS28-CRP, DAS28-ESR) in these two groups of patients. Both Buc and SASP were shown to be efficacious within 3 months after the start of treatment. Both drugs were found to be suitable as first-line treatment of early RA. Signs of efficacy tended to occur earlier with Buc than with SASP, and Buc also tended to have higher efficacy than SASP.     

Revisión sistemática del uso de metotrexato por vía parenteral en enfermedades reumáticas

ObjectiveTo analyse the efficacy, adherence, patient satisfaction, safety, pharmacodynamics and cost-effectiveness of parenteral methotrexate (MTX) in patients with rheumatic diseases.MethodsA systematic review of literature was carried out in Medline, Embase and Cochrane Central from the beginning until June 2019. Studies including adult patients with rheumatic diseases being treated with parenteral MTX were identified and data on efficacy, adherence, satisfaction, safety, pharmacokinetics, and cost-effectiveness analysed. As for the designs, systematic reviews, clinical trials, or observational studies were permitted, including cross-sectional and small-sample studies if they were pharmacokinetic studies.ResultsOut of 4160 identified articles, 80 articles were finally included. The efficacy profile of parenteral MTX seems useful in general and in those patients with insufficient response to oral MTX. The parenteral route does not seem to increase the rate or severity of adverse events due to the use of MTX. The use of parenteral MTX is an appropriate way to reduce costs in patients with inadequate response to oral MTX. Adherence and satisfaction are favoured by training programmes in the use of the parenteral route. The results in rheumatic diseases other than rheumatoid arthritis (RA) are very scarce and do not enable obtaining conclusive data.ConclusionsParenteral MTX can be an alternative to the use of oral MTX, due to its profile of efficacy, safety, adherence and pharmacoeconomic results, especially in those patients with RA.     

Serum levels and pharmacodynamics of methotrexate and its metabolite 7-hydroxy methotrexate in Japanese patients with rheumatoid arthritis treated with 2-mg capsule of methotrexate three times per week

Abstract

Methotrexate (MTX) is the first-choice drug for rheumatoid arthritis (RA); however, the pharmacodynamics of MTX in Japanese patients with RA treated legitimately according to the government recommended dosage, 6?mg per week, are unknown. Methotrexate and its metabolite, 7-hydroxy MTX (7-OH MTX), were measured in sera of 16 outpatients with active RA in the first week of MTX treatment and 4–12 weeks after the introduction at 0, 1, 2, 4, and 8?h after administration of the first and the third 2-mg capsule, followed by sampling at 48, 96, and 168?h. The mean maximal serum drug concentration (mean C_max) of MTX attained at 1–2?h after ingestion of the first capsule was 0.215 and 0.252?µM, respectively, in the first and the follow-up week. The mean C_max after ingestion of the third capsule was 0.223?µM and 0.357?µM. The mean C_max of 7-OH MTX was 0.0334 and 0.0289?µM for the first capsule, and 0.0495 and 0.0672?µM for the third capsule. The results indicate that MTX does not accumulate or deposit in the body of Japanese patients with RA when treated with 6?mg per week, and pharmacodynamics of MTX are comparable to those in overseas patients treated with 7.5?mg per week.     

Pneumocystis jiroveci pneumonia associated with low-dose methotrexate treatment for rheumatoid arthritis: report of two cases and review of the literature

Low-dose methotrexate (MTX) therapy is widely used for rheumatoid arthritis (RA) because of its favorable efficacy and toxicity profile. Although Pneumocystis jiroveci pneumonia (PCP) is most often seen in severely immunosuppressed patients, PCP complicating low-dose MTX therapy for RA has been reported to sometimes occur. We herein report two cases of patients who developed PCP during treatment with low-dose MTX, and discuss the importance of prophylaxis for this opportunistic infection.     

A comparative study of the effects of bucillamine and salazosulfapyridine in the treatment of rheumatoid arthritis

Bucillamine (Buc), developed in Japan, is a disease-modifying antirheumatic drug (DMARD) which has been used to treat numerous patients with rheumatoid arthritis (RA) in Japan and Korea with favorable results. However, it has not been used globally. In the present study, we compared the timing of onset of efficacy and the usefulness of this drug with that of the globally accepted agent salazosulfapyridine (SASP). There were 26 patients in the Buc group and 23 in the SASP group. We compared changes in the number of swollen joints, number of painful joints, duration of morning stiffness, grip strength, levels of inflammatory marker [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)], rheumatoid factor (RF), physician’s rating by visual analogue scale (VAS), patient’s rating of pain, patient’s overall rating (VAS), and improvement according to European League against Rheumatism (EULAR) criteria (DAS28-CRP, DAS28-ESR) in these two groups of patients. Both Buc and SASP were shown to be efficacious within 3 months after the start of treatment. Both drugs were found to be suitable as first-line treatment of early RA. Signs of efficacy tended to occur earlier with Buc than with SASP, and Buc also tended to have higher efficacy than SASP.     

Phase III,multicenter, open-label,long-term study of the safety of abatacept in Japanese patients with rheumatoid arthritis and an inadequate response to conventional or biologic disease-modifying antirheumatic drugs

Abstract

Objectives. To examine the long-term safety of intravenous (IV) abatacept treatment in Japanese patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) or other conventional or biologic disease-modifying antirheumatic drugs.

Methods. This Phase III, open-label, long-term study (NCT00484289) comprised Japanese patients with RA who had completed abatacept Phase I or Phase II studies, and new patients intolerant to MTX. Patients from Phase I and Phase II studies received a weight-tiered dosing equivalent of 10 mg/kg abatacept, with MTX at doses up to 8 mg/week; newly enrolled patients received weight-tiered 10 mg/kg abatacept monotherapy. Safety and efficacy were assessed.

Results. A total of 217 patients (Phase I, n = 13; Phase II, n = 178; newly enrolled, n = 26) were treated with IV abatacept for a mean of 3 years. Serious adverse events occurred in 67/217 (30.9%) patients. Most adverse events were mild or moderate. For all cohorts combined, American College of Rheumatology 20% response rates ranged from 61.3 to 81.8% for as-observed and last observation carried forward analyses over 192 weeks. Following initial response, clinical and functional outcomes were maintained for up to 3 years.

Conclusions. In Japanese patients with RA, IV abatacept with and without background MTX showed tolerable safety and sustained efficacy over 3 years.     

Factors predicting the response to low-dose methotrexate therapy in patients with rheumatoid arthritis: a better response in male patients

Abstract

Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) throughout the world. In Japan, MTX is recommended by the Japanese Ministry of Health, Labour, and Welfare to be given as the second or third DMARD and at a dosage of no more than 8?mg/week. We analyzed the efficacy of MTX in Japanese patients with RA in order to determine whether it is comparable to that in Western countries, where 15–20?mg/week of MTX is used, as well as to elucidate the factors associated with the favorable response to MTX. Around 8?mg/week of MTX was effective in half of the RA patients in the current study, and male sex was the only factor associated with a good response to MTX from a multivariate regression model analysis. Some of the patients who had a poor response to MTX showed an improvement with the addition of bucillamine or prednisolone. For the remaining patients, an increase in the MTX dosage to more than 8?mg/week or the use of biologics such as the anti-tumor necrosis factor (TNF)-α monoclonal antibody may be required.     

Efficacy and safety of 10-deazaaminopterin in the treatment of rheumatoid arthritis: A one-year continuation,double-blind study

Objective. To determine the long-term safety and efficacy of 10-deazaaminopterin (10-DAM) in the treatment of rheumatoid arthritis (RA). Methods. A 1-year continuation of an initial 15-week randomized, double-blind clinical trial of 10-DAM and methotrexate (MTX). Results. 10-DAM (n = 10) and MTX (n = 8) had comparable safety and efficacy profiles. One 10-DAM—treated and 2 MTX-treated patients experienced transient side effects; 1 MTX-treated patient experienced recurrent nausea and discontinued MTX. Conclusion. 10-DAM appears to be as beneficial and as safe as MTX for the treatment of RA.     

Acceptability and usefulness of mizoribine in the management of rheumatoid arthritis in methotrexate-refractory patients and elderly patients,based on analysis of data from a large-scale observational cohort study

Abstract

This report documents the results of a study performed to examine clinical use of mizoribine (MZR), using data from a large-scale prospective cohort study, IORRA (Institute of Rheumatology Rheumatoid Arthritis). The number of patients with RA entered in this study from October 2000 through October 2003 was 6238. Three hundred and six patients (4.9%) received MZR therapy. Mizoribine users who were taking methotrexate (MTX) (MTX–MZR group, n = 94) and over 70 years of age (elderly group, n = 45) were collected. Cumulative retention rates of MZR were calculated by Kaplan–Meier analysis. Median drug survival of MZR was 28 months for the poor responders to MTX and 43 months for the poor responders to MZR, with no significant difference between these groups. Cumulative retention rate of MZR in the elderly group did not show a significant difference compared to that in patients aged under 70 years. Ten patients (10.6%) in the MTX–MZR group and 10 patients (22.2%) in the elderly group experienced adverse effects of MZR. None of these adverse effects was serious. This study indicated that, although MZR has not been frequently prescribed for RA patients, it may be useful and relatively safe for patients who are poor responders to MTX as an additional regimen to MTX therapy as well as for elderly patients.     

Serum levels and pharmacodynamics of methotrexate and its metabolite 7-hydroxy methotrexate in Japanese patients with rheumatoid arthritis treated with 2-mg capsule of methotrexate three times per week

Methotrexate (MTX) is the first-choice drug for rheumatoid arthritis (RA); however, the pharmacodynamics of MTX in Japanese patients with RA treated legitimately according to the government recommended dosage, 6 mg per week, are unknown. Methotrexate and its metabolite, 7-hydroxy MTX (7-OH MTX), were measured in sera of 16 outpatients with active RA in the first week of MTX treatment and 4–12 weeks after the introduction at 0, 1, 2, 4, and 8 h after administration of the first and the third 2-mg capsule, followed by sampling at 48, 96, and 168 h. The mean maximal serum drug concentration (mean C_max) of MTX attained at 1–2 h after ingestion of the first capsule was 0.215 and 0.252 μM, respectively, in the first and the follow-up week. The mean C_max after ingestion of the third capsule was 0.223 μM and 0.357 μM. The mean C_max of 7-OH MTX was 0.0334 and 0.0289 μM for the first capsule, and 0.0495 and 0.0672 μM for the third capsule. The results indicate that MTX does not accumulate or deposit in the body of Japanese patients with RA when treated with 6 mg per week, and pharmacodynamics of MTX are comparable to those in overseas patients treated with 7.5 mg per week.     

Safety and efficacy of combination therapy of iguratimod with methotrexate for patients with active rheumatoid arthritis with an inadequate response to methotrexate: An open-label extension of a randomized,double-blind,placebo-controlled trial

Abstract

Objective. To obtain safety and efficacy data on combination treatment with iguratimod and methotrexate (MTX) in an open-label extension study in patients with active rheumatoid arthritis (RA).

Methods. Following a 28-week, randomized, double-blind trial of adding iguratimod or placebo to stable MTX therapy, patients entered a 24-week extension. Patients randomized to the iguratimod + MTX group continued treatment. Patients treated with placebo + MTX switched to iguratimod + MTX [the (placebo/iguratimod) + MTX group].

Results. In the iguratimod + MTX group, the rate of 20% improvement in American College of Rheumatology criteria (ACR20) at week 52 (71.3%) was similar to that at week 24 (69.5%). ACR50, ACR70 and Health Assessment Questionnaire Disability Index at week 52 significantly improved compared with the values at week 24. In the (placebo/iguratimod + MTX) group, the switch to iguratimod treatment significantly improved ACR20 from 30.7% at week 24 to 72.1% at week 52. Frequent adverse events for 52 weeks in the iguratimod + MTX group were nasopharyngitis, upper respiratory tract inflammation, stomatitis, lymphocyte decrease, AST increase, ALT increase and blood iron decrease. These adverse events were predominantly mild or moderate in severity. No deaths occurred.

Conclusion. Efficacy and tolerance of iguratimod + MTX therapy was maintained to 52 weeks in patients with active RA with inadequate response to MTX.     

Discontinuation of methotrexate in rheumatoid arthritis patients achieving clinical remission by treatment with upadacitinib plus methotrexate (DOPPLER study): A study protocol for an interventional,multicenter, open-label and single-arm clinical trial with clinical,ultrasound and biomarker assessments

Background:The administration of Janus kinase inhibitors as well as biological disease-modifying anti-rheumatic drugs has dramatically improved the clinical outcomes of patients with rheumatoid arthritis (RA). Previous trials have shown that upadacitinib, a Janus kinase inhibitor, can effectively improve disease activity and prevent progression of joint destruction in RA patients with inadequate responses to methotrexate (MTX). It remains unclear whether reduced disease activity can be maintained after discontinuation of MTX in patients treated with upadacitinib plus MTX. Thus, the aim of this study is to evaluate changes in disease activity after administration of upadacitinib plus MTX in RA patients who failed to achieve an adequate response to MTX and to determine whether clinical relapse can be avoided after discontinuation of MTX in those who achieved clinical remission.Methods/design:The proposed study is an interventional, multicenter, open-label, single-arm clinical trial with a 48-week follow-up. The cohort will include 155 RA patients with at least moderate disease activity during treatment with MTX. Patients will receive upadacitinib and MTX will be discontinued for those who achieve clinical remission. Disease activity will be evaluated longitudinally by measuring clinical disease activity indices and with musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who sustain a disease activity score-28- C reactive protein score of ≤3.2 from week 24 to 48 after a disease activity score-28- C reactive protein score of <2.6 at week 24. Important secondary endpoints are changes from baseline MSUS scores. Serum levels of multiple biomarkers, including cytokines and chemokines, will be comprehensively analyzed.Discussion:The study results are expected to show the clinical benefit of the discontinuation of MTX after achieving clinical remission by treatment with upadacitinib plus MTX combination therapy. The strength of this study is the prospective evaluation of therapeutic efficacy using clinical disease activity indices and standardized MSUS, which can accurately and objectively evaluate disease activity at the joint level among patients drawn from multiple centers. Furthermore, parameters to predict clinical remission after administration of upadacitinib plus MTX combination therapy and nonclinical relapse after discontinuation of MTX will be screened by integrated multilateral assessments (i.e., clinical disease activity indices, MSUS findings, and serum biomarkers).     

Gynecomastia associated with low-dose methotrexate therapy for rheumatoid arthritis

Abstract

A 68-year-old man with a 3-year history of rheumatoid arthritis (RA) developed gynecomastia 3 months after beginning oral low-dose methotrexate (MTX) therapy. Four months after MTX therapy was discontinued, the gynecomastia symptoms improved. Only eight cases of gynecomastia resulting from low-dose MTX administration have been reported worldwide, and no cases have previously been reported in Japan. Although it occurs infrequently, gynecomastia resulting from low-dose MTX therapy should be considered in male patients with RA.     

Are <Emphasis Type="Italic">Thymidylate synthase</Emphasis> and <Emphasis Type="Italic">Methylene tetrahydrofolate reductase</Emphasis> genes linked with methotrexate response (efficacy,toxicity) in Indian (Asian) rheumatoid arthritis patients?

Methotrexate (MTX) is among the best-tolerated disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis (RA); major drawbacks of MTX therapy are the large interpatient variability in clinical response and the unpredictable appearance of a large spectrum of side effects. Several studies have demonstrated gene polymorphism that may regulate intracellular methotrexate metabolic pathway enzymes linked to drug efficacy and safety, but the evidence available is not yet conclusive. We decided to run a pilot study to determine the incidence of Methylene tetrahydrofolate (MTHFR; C677T, A1298C) and Thymidylate synthase (TS; 5′ UTR repeat, 3′ UTR deletion) gene polymorphism in rheumatoid arthritis patients in our community (Indian Asian) and further explore its association with MTX response (efficacy, toxicity). Thirty-four naïve RA patients on supervised MTX therapy and 139 healthy controls were genotyped for A1298C and C677T polymorphism of the MTHFR gene and 5′ UTR repeat and 3′ UTR deletion polymorphism of the TYMS gene by polymerase chain reaction-restriction fragment length polymorphism. Association, if any, between gene polymorphism and MTX response in RA patients was analyzed. The MTHFR A1298C ‘C’ allele incidence among RA patients (46%) was significantly higher (χ ²?=?4.24, P?相似文献   

Effectiveness and Safety of Golimumab for Patients ≥75 Years Old with Rheumatoid Arthritis

ObjectiveTreatment of elderly patients with rheumatoid arthritis (RA) has been controversial because they often have serious comorbidities and cannot use methotrexate (MTX). In Japan, golimumab (GLM) 100 mg without MTX is approved. We investigated the effectiveness and safety of GLM in elderly patients with RA. Methods The GLM survival rate was evaluated using the Kaplan-Meier method. Disease activities, laboratory findings, and treatments were evaluated. Patients We enrolled 168 patients with RA in our hospital. Using age ≥75 years old to identify elderly patients, younger (n=111) and elderly (n=57) groups were established. Elderly patients were divided into 2 groups according to the MTX treatment status (with, n=27; without, n=25). Results The GLM survival rates were 80.8% and 82.3% in elderly and younger patients, respectively (p=0.762). At 52 weeks, the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) was improved in elderly patients (4.26 vs. 3.31, p＜0.001); the Health Assessment Questionnaire Disability Index (HAQ-DI) was unchanged (1.12 vs. 0.88, p=0.694). When elderly patients were compared according to the MTX treatment status, the DAS28-ESR had improved in both groups (with MTX: 3.82 vs. 2.68, p＜0.001; without MTX: 4.76 vs. 4.25, p=0.026); however, the HAQ-DI had not. The GLM survival rates at 52 weeks were 85% and 76% in patients with and without MTX, respectively. Conclusion In elderly patients with RA, GLM was effective, regardless of MTX treatment status, but it did not affect the HAQ-DI. GLM survival rates were comparable between elderly and younger patients. GLM may be a suitable option for elderly patients with RA who cannot use MTX.     

Methotrexate can prevent cardiovascular events in patients with rheumatoid arthritis: An updated meta-analysis

Aims:The incidence of cardiovascular events (CVEs) in patients with rheumatoid arthritis (RA) is higher than that in people without RA. This may be because inflammation promotes the progression of atherosclerosis. Anti-inflammatory drugs might reduce the occurrence of CVEs in patients with RA. Methotrexate (MTX) is a conventional synthetic anti-rheumatic drug that is widely used in the treatment of RA. We performed a meta-analysis to determine whether MTX can prevent CVEs in RA patients. Then, we discussed the possibility of using MTX to prevent recurred CVEs in patients with coronary heart disease (CHD).Methods:We searched PubMed, Embase, Web of Science, and the Cochrane Library using the key words “methotrexate,” “cardiovascular,” “acute coronary syndrome,” “coronary heart disease,” “myocardial infarction,” “angina pectoris,” and “rheumatoid arthritis.” The efficacy outcome was defined as a composite of CVEs, including stable angina, acute coronary syndrome, stroke, heart failure, and cardiac death.Results:A total of 10 studies and 195,416 RA patients were included in our meta-analysis, and the effect size of relative risk (RR) was pooled using a fixed effect model. The results showed that MTX prevented CVEs in RA patients (RR: 0.798, 95% CI 0.726–0.876, P = .001, I² = 27. 9%).Conclusion:MTX can prevent CVEs in RA patients, but there is not sufficient evidence for using MTX to treat patients with CHD.     

Efficacy and safety of tofacitinib in Japanese patients with rheumatoid arthritis by background methotrexate dose: A post hoc analysis of clinical trial data

Abstract

Objectives: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). We investigated concomitant methotrexate (MTX) dose on tofacitinib efficacy/safety in Japanese RA patients.

Methods: This post hoc analysis pooled data from a 3-month phase 2 study (NCT00603512) and a 24-month phase 3 study (NCT00847613). Patients (N= 254) received tofacitinib (low-dose (1 or 3?mg), 5?mg, 10?mg) twice daily (BID) or placebo, with low-dose (>0 to 8?mg/week) or high-dose (>8?mg/week) MTX. Efficacy (ACR20/50/70 and DAS28-4 (ESR)<2.6 response rates; changes from baseline (CFB) in DAS28-4 (ESR) and HAQ-DI) and safety (adverse events (AEs), discontinuations due to AEs, serious AEs, and deaths) were assessed through month 3.

Results: At month 3, ACR20/50/70 response rates, mean DAS28-4 (ESR) CFB and HAQ-DI CFB were similar across MTX doses and generally greater for all tofacitinib doses versus placebo. AE rates with low-dose/high-dose MTX were: placebo, 28.6%/52.9%; tofacitinib low-dose, 50.0%/66.7%; 5?mg BID, 56.5%/64.3%; 10?mg BID, 73.8%/67.7%.

Conclusion: Tofacitinib efficacy in Japanese RA patients may be unaffected by background MTX dose. AE rates with low-dose versus high-dose MTX were lower with placebo, tofacitinib low-dose or 5?mg BID, but not 10?mg BID, with no apparent differences across system organ class/laboratory parameters.