Dataset Information

Tofacitinib, an oral Janus kinase inhibitor, in patients from Brazil with rheumatoid arthritis: Pooled efficacy and safety analyses.

ABSTRACT:

Background

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Efficacy and safety of tofacitinib in Brazilian patients from Phase 2 (P2) and Phase 3 (P3) global studies of up to 24 months' duration were evaluated.

Methods

Data were pooled from Brazilian patients with RA and an inadequate response to conventional synthetic or biologic disease-modifying antirheumatic drugs enrolled in P2/P3 tofacitinib studies who received tofacitinib 5 or 10 mg twice daily (BID), or placebo, as monotherapy or in combination with methotrexate. Efficacy, safety, and patient-reported outcomes were assessed over 24 months.

Results

Patients (226) from Brazil were treated in tofacitinib global P2/P3 studies. At Month 3, there were improvements in American College of Rheumatology 20/50/70 response rates, Disease Activity Score in 28 joints, erythrocyte sedimentation rate, and Health Assessment Questionnaire-Disability Index scores with both tofacitinib doses. Improvements from baseline in pain, fatigue, and health-related quality of life with tofacitinib 5 and 10 mg BID were reported. Efficacy improvements were sustained up to Month 24. The most frequent class of adverse events was infections and infestations. No cases of tuberculosis or other opportunistic infections were reported.

Conclusion

In a Brazilian subpopulation of patients with RA, tofacitinib reduced disease signs and symptoms and improved physical function up to Month 24, with a safety profile consistent with findings from global studies.

SUBMITTER: Lomonte ABV

PROVIDER: S-EPMC6081087 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Tofacitinib, an oral Janus kinase inhibitor, in patients from Brazil with rheumatoid arthritis: Pooled efficacy and safety analyses.

Lomonte Andrea B V ABV Radominski Sebastião C SC Marcolino Flora M D FMD Brenol Claiton V CV Zerbini Cristiano A F CAF García Erika G EG Akylbekova Ermeg L EL Rojo Ricardo R de Leon Dario Ponce DP

Medicine 20180801 31

<h4>Background</h4>Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Efficacy and safety of tofacitinib in Brazilian patients from Phase 2 (P2) and Phase 3 (P3) global studies of up to 24 months' duration were evaluated.<h4>Methods</h4>Data were pooled from Brazilian patients with RA and an inadequate response to conventional synthetic or biologic disease-modifying antirheumatic drugs enrolled in P2/P3 tofacitinib studies who received tofacitinib 5 or ...[more]

PMID: 30075534

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Project description:IntroductionIn Australia, there is an unmet need for improved treatments for rheumatoid arthritis (RA). Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. To provide an overview of key study outcomes for tofacitinib in Australian patients, we analyzed the efficacy and safety of tofacitinib in the Australian subpopulation of global RA phase III and long-term extension (LTE) studies.MethodsData were pooled from the Australian subpopulation of four phase III studies and one LTE study (database not locked at cut-off date: January 2016). Patients in the phase III studies received tofacitinib 5 or 10 mg twice daily (BID), placebo (advancing to tofacitinib at months 3 or 6), or adalimumab, with background methotrexate or conventional synthetic disease-modifying antirheumatic drugs. Patients in the LTE study received tofacitinib 5 or 10 mg BID. Efficacy endpoints were American College of Rheumatology (ACR) 20/50/70 response rates, and change from baseline in the Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores. Safety endpoints included incidence of adverse events (AEs), serious AEs, and discontinuations due to AEs. AEs of special interest and laboratory parameters were analyzed in the LTE study.ResultsAcross phase III studies (N = 100), ACR response rates and improvements in DAS28-4(ESR) and HAQ-DI scores were numerically greater with tofacitinib vs. placebo at month 3, and increased until month 12. The results were sustained in the LTE study (N = 99) after 60 months' observation. In general, the efficacy and safety profiles of tofacitinib were similar to those of the global RA population.ConclusionsIn Australian patients with RA, tofacitinib therapy demonstrated sustained efficacy and consistent safety over ≥ 60 months' treatment.FundingPfizer Inc. TRIAL REGISTRATION NUMBERS (ALL CLINICALTRIALS.GOV): NCT00960440; NCT00847613; NCT00856544; NCT00853385; NCT00413699.

Project description:BackgroundTofacitinib 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.MethodsStudy 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.ResultsA 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.ConclusionsTofacitinib (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.Trial registrationClinicaltrials.gov NCT00661661 . Registered 7 February 2008.

Project description:The aim of the present study was to conduct a meta-analysis of the effectiveness of tofacitinib, a novel oral Janus kinase inhibitor, recently approved for the treatment of active rheumatoid arthritis in patients who have failed previous treatment with methotrexate (MTX) or other disease-modifying antirheumatic drugs (DMARDs). A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library, and other databases till 3 May 2013. All included studies were analyzed with the use of the Review Manager 5.1.0. software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement protocol. Nine randomized controlled trials (RCTs) comparing tofacitinib with placebo were identified. Two of them additionally provided the comparison with adalimumab. However, only eight RCTs met the inclusion criteria for the meta-analysis. The overall results of the meta-analysis showed that tofacitinib provided a statistically significant improvement according to the response criteria (ACR20/50/70) after 12 weeks of treatment when compared to placebo (p < 0.00001). Moreover, it was demonstrated that tofacitinib was significantly superior to adalimumab in achieving the ACR50 response criteria at week 12 (p = 0.003). For the safety analysis, there were no statistically significant differences between tofacitinib-, adalimumab-, and placebo-treated patients in respect to the risk of serious adverse events or treatment discontinuation due to adverse reactions (p > 0.05). The findings of this systematic review with meta-analysis indicate that tofacitinib monotherapy or with background methotrexate provides early statistically significant and clinically important improvement in rheumatoid arthritis symptoms and has an acceptable safety profile comparable to that of placebo. The results of the present meta-analysis show that the frequency of serious adverse events was not increased after tofacitinib treatment. In addition, tofacitinib might provide an effective treatment option compared to intravenous or subcutaneous biological DMARDs, as suggested by the result of the comparison made regarding tofacitinib vs. adalimumab ACR50 response rate.

Project description:AimWe report tofacitinib efficacy and safety in Asia-Pacific patients who participated in the rheumatoid arthritis (RA) clinical development program.MethodThis post-hoc analysis included pooled data from patients with RA in the Asia-Pacific region treated with tofacitinib with/without conventional synthetic disease-modifying antirheumatic drugs in Phase (P)1, 2, 3, and long-term extension (LTE) studies (one LTE ongoing; January 2016 data-cut). Efficacy was assessed over 24 months in patients who received tofacitinib 5 (N = 397) or 10 (N = 382) mg twice daily or placebo (N = 243) in three P2 and five P3 studies. Endpoints included American College of Rheumatology (ACR)20/50/70 responses, Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) and Clinical Disease Activity Index (CDAI) remission rates, and change from baseline in Health Assessment Questionnaire-Disability Index (∆HAQ-DI). Safety data pooled over 92 months from one P1, four P2, six P3, and two LTE studies for all tofacitinib doses (N = 1464) included incidence rates (IRs) (patients with events/100 patient-years) for adverse events (AEs) of special interest.ResultsAt month 3, patients receiving tofacitinib 5/10 mg twice daily improved vs placebo in ACR20 (69.2%/77.9% vs 27.5%), ACR50 (36.9%/44.4% vs 9.5%), and ACR70 (15.1%/22.4% vs 2.7%) responses, remission rates for DAS28-4(ESR) (8.5%/18.5% vs 2.6%) and CDAI (6.1%/12.3% vs 0.5%), and ∆HAQ-DI (-0.5/-0.6 vs -0.1); improvements were sustained through 24 months. IRs (95% CI) were 9.4 (8.5, 10.3) for serious AEs, 9.1 (8.3, 10.1) for discontinuations due to AEs, 3.7 (3.2, 4.3) for serious infections, 5.9 (5.2, 6.7) for herpes zoster, and 0.8 (0.6, 1.1) for malignancies (excluding non-melanoma skin cancer).ConclusionIn Asia-Pacific patients, tofacitinib improved signs/symptoms over 24 months. Safety over 92 months was generally consistent with global tofacitinib studies; however, infection IRs were higher in Asia-Pacific patients.

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:Introduction/objectiveTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This post-hoc analysis evaluated the effect of temporary discontinuation and reinitiation of tofacitinib on disease control in patients with RA in the vaccine sub-study of the long-term extension (LTE) study ORAL Sequel (NCT00413699).MethodsThe sub-study of ORAL Sequel was a randomized, parallel-group, open-label study. Patients who received tofacitinib 10 mg twice daily for ≥ 3 months in ORAL Sequel were randomized to receive continuous (tofacitinib monotherapy/with methotrexate) or interrupted (tofacitinib withdrawn for 2 weeks post-randomization then reinitiated as monotherapy/with methotrexate) treatment. Efficacy assessments included ACR20/50/70 response rates, change from baseline (∆) in C-reactive protein (CRP), Health Assessment Questionnaire-Disability Index (HAQ-DI), Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4 [ESR]), Clinical Disease Activity Index (CDAI), Patient Global Assessment of arthritis (PtGA), Pain (Visual Analog Scale [VAS]), and Physician Global Assessment of arthritis (PGA). Safety was assessed throughout.ResultsThe sub-study included 99 patients each in the continuous and interrupted treatment groups. ACR20/50 response rates, ∆CRP, ∆HAQ-DI (day 15), ∆DAS28-4 (ESR), ∆CDAI, ∆PtGA, ∆Pain (VAS), and ∆PGA were significantly worse in interrupted vs continuous patients during dose interruption, but were generally similar to pre-interruption/continuous treatment levels 28 days post-reinitiation. A numerically higher proportion of interrupted patients reported adverse events (49.5%) vs continuous patients (35.4%).ConclusionsTofacitinib efficacy can be re-established after temporary withdrawal and reinitiation. The safety profile of patients who temporarily discontinued tofacitinib in the sub-study was consistent with previous tofacitinib LTE studies over 9 years.Clinical trial registration numberNCT00413699 Key Points • In this sub-study of the long-term extension (LTE) study, ORAL Sequel, the efficacy of tofacitinib was re-established after temporary withdrawal (2 weeks) and reinitation of treatment in patients with RA. • Patients with RA who temporarily discontinued tofacitinib had similar safety events to those reported in previous LTE studies. • The results of this sub-study were consistent with a post-hoc analysis of pooled data from two LTE studies, ORAL Sequel and A3921041, which assessed the efficacy of tofacitinib following a treatment discontinuation period of 14-30 days.

Project description:OBJECTIVE:To create a mobile application able to help patients follow medical treatments properly. METHODS:We designed and developed a custom Android/iOS App to remind patients of the pharmaceutical drugs to be taken, of the visits and exams to attend, and to detect their compliance with their personal therapeutic plan. In this paper we describe the App development, UX/UI design, Gamification. TuTOR is an Android and iOS application designed to remind patients of the drugs to be taken, giving them all the information related to their therapeutic plans in a simple and non-invasive way. Thanks to a dedicated back-office, specially designed to meet specific medical information needs, the App can also help physicians detect their patients' compliance with their treatments and modify prescriptions in real time. The App also ensures a state-of-the-art approach to data security and privacy protection. The main feature of TuTOR is the smart therapy assistant, which features dedicated alarms to remind users of taking their prescription drugs. Thanks to the automatic synchronization with a local database, the alert system works even without connection to the Internet. Particular attention was paid during the App's design process: we looked to create an intuitive interface to ensure absolute ease of use, with state-of-the-art visual design aimed at maximizing user experience. Other relevant features include the App's ability to givevisual evidence of the most important drugs to be taken and its note-taking feature, which gives patients the possibility to note down indications on why a specific drug was skipped. The App also keeps track of upcoming medical exams, laboratory tests, and visits on a devoted calendar. It also helps patients by listing therapy contacts, such as physicians' phone numbers, and indicates all medical references by showing, for example, locations of relevant clinics and pharmacies on a map. Thanks to specific visual progress indicators and an innovative gamification approach, the App encourages users to faithfully follow therapy guidelines. With TuTOR, assessing the therapy's state of completion is quick and easy.Thanksto the privacy-by-design approach used, all data managed by the system is compliant with the European Privacy Regulation and it is not available to third parties. EXPECTED RESULTS:A mobile App for medication adherence might increase objectively and subjectively measured adherence.

Dataset Information

Tofacitinib, an oral Janus kinase inhibitor, in patients from Brazil with rheumatoid arthritis: Pooled efficacy and safety analyses.

Background

Methods

Results

Conclusion

Publications

Tofacitinib, an oral Janus kinase inhibitor, in patients from Brazil with rheumatoid arthritis: Pooled efficacy and safety analyses.

Similar Datasets

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