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Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis.

ABSTRACT: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24?months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration <1?year) versus established (?1?year) RA.MTX-naive patients ?18?years with active RA received tofacitinib monotherapy (5 or 10?mg two times a day, or MTX monotherapy, in a 24-month Phase 3 trial.Of 956 patients (tofacitinib 5?mg two times a day, n=373; tofacitinib 10?mg two times a day, n=397; MTX, n=186), 54% had early RA. Baseline disease activity and functional disability were similar in both groups; radiographic damage was greater in patients with established RA. At month 24, clinical response rates were significantly greater in patients with early versus established RA in the tofacitinib 5?mg two times a day group. Both tofacitinib doses had greater effects on clinical, functional and radiographic improvements at 1?and 2?years compared with MTX, independent of disease duration. No new safety signals were observed.Treatment response was generally similar in early and established RA; significantly greater improvements were observed at month 24 with tofacitinib 5?mg two times a day in early versus established RA. Tofacitinib 5 and 10?mg two times a day demonstrated greater efficacy versus MTX irrespective of disease duration. No difference in safety profiles was observed between patients with early or established RA.NCT01039688; Results.

SUBMITTER: Fleischmann RM

PROVIDER: S-EPMC4964179 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis.

Fleischmann Roy M RM Huizinga Tom W J TW Kavanaugh Arthur F AF Wilkinson Bethanie B Kwok Kenneth K DeMasi Ryan R van Vollenhoven Ronald F RF

RMD open 20160726 2

<h4>Introduction</h4>Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration <1 year) versus established (≥1 year) RA.<h4>Methods< ...[more]

PMID: 27493790

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Project description:ObjectiveThe SELECT-EARLY trial was undertaken to study the effect of upadacitinib, an oral, reversible Janus kinase 1-selective inhibitor, as monotherapy in patients with predominantly early rheumatoid arthritis who were naive for or had limited exposure to methotrexate (MTX).MethodsPatients (n = 947) were randomized 1:1:1 to receive once-daily doses of upadacitinib 15 mg or 30 mg or weekly MTX (7.5-20 mg/week) for 24 weeks. The primary end points were the proportion of patients who met the American College of Rheumatology 50% (ACR50) improvement criteria at week 12, and the proportion in whom a Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) of <2.6 was achieved at week 24. Data are presented through week 24.ResultsAt baseline, the median disease duration was 0.5 years (range 0-44 years). A total of 840 patients (89%) completed 24 weeks of treatment. The study met both primary end points for upadacitinib 15 mg and 30 mg versus MTX (ACR50 was achieved at week 12 in 52% and 56% of patients, respectively, versus 28% [P < 0.001], and DAS28-CRP <2.6 was achieved at week 24 in 48% and 50% of patients, respectively, versus 19% [P < 0.001]). Statistically significant and clinically meaningful improvements in multiple patient-reported outcomes (PROs) were recorded for both upadacitinib doses versus MTX. Overall, 88% of patients receiving upadacitinib 15 mg and 89% of patients receiving 30 mg, respectively, had no radiographic progression (modified total Sharp score ≤0) compared to 78% of those receiving MTX (P < 0.01). Through week 24, the frequency of treatment-emergent adverse events was similar between the MTX arm (65%) and upadacitinib 15 mg arm (64%), but was slightly higher in the upadacitinib 30 mg arm (71%). Six deaths were reported (2 in the upadacitinib 15 mg arm, 3 in the upadacitinib 30 mg arm, and 1 in the MTX arm).ConclusionOur findings indicate that patients receiving either dose of upadacitinib monotherapy experienced significant improvements in clinical, radiographic, and PROs compared to patients receiving MTX.

Project description:BackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies.MethodsORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ?1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout.ResultsORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population.ConclusionsTofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population.Clinical trial identifierNCT00856544 and NCT00413699.

Project description:Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Here, tofacitinib safety and efficacy data from a long-term extension study in Japanese patients are presented.Study A3921041 was a multi-centre, open-label, long-term extension study that included Japanese patients who had participated in a prior Phase 2 or Phase 3 study of tofacitinib as monotherapy or with background methotrexate. Patients received tofacitinib 5 mg twice daily (BID) or tofacitinib 10 mg BID. Dose adjustment of tofacitinib during treatment period, and concomitant usage of disease-modifying antirheumatic drugs including methotrexate after week 12 were permitted. Primary endpoints were adverse events, laboratory parameters and vital signs. Secondary efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate (ESR))<2.6 response rate (DAS-defined remission) and Health Assessment Questionnaire-Disability Index (HAQ-DI) score. Safety and efficacy data were assessed throughout the study.A total of 486 patients were recruited and treated (1439.9 patient-years of exposure). 308 patients completed the study. Median (range) duration of treatment in this extension study was 1185 (5-2016) days. 476 patients (97.9 %) experienced adverse events; the majority of which (97.8 %) were of mild or moderate severity. The two most common treatment-emergent adverse events were nasopharyngitis (n?=?293, 60.3 %) and herpes zoster (n?=?94, 19.3 %). For all tofacitinib-treated patients, the incidence rate (patients with events per 100 patient-years) was 10.7 for serious adverse events, 3.3 for serious infections, 7.4 for herpes zoster (serious and non-serious) and 1.2 for malignancies (excluding non-melanoma skin cancer). Mean changes from baseline (start of the index study) in laboratory parameters were consistent with those seen in previously reported studies of tofacitinib. ACR20/50/70 response rates, DAS-defined remission rates and HAQ-DI scores were sustained through to study completion.Tofacitinib (with or without background methotrexate) demonstrated a stable safety profile and sustained efficacy in Japanese patients with active rheumatoid arthritis. The risk of herpes zoster appears to be higher in Japanese patients treated with tofacitinib than in the global population.Clinicaltrials.gov NCT00661661 . Registered 7 February 2008.

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.

Dataset Information

Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis.

Publications

Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis.

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