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Introduction Global prevalence estimates for chronic kidney disease (CKD) in rheumatoid arthritis (RA) vary. This study assessed real-world prevalence estimates of renal impairment, based on estimated glomerular filtration rate (eGFR), among commercially insured patients with RA in the United States (US). Methods In this retrospective cohort study, we used administrative claims data from the HealthCore Integrated Research Database (HIRD®) between January 2013 and December 2018. Adult patients with ≥ 2 claims for RA and ≥ 2 serum creatinine (SCr) measurements ≥ 90 days apart on or after the index date were included. eGFR was calculated per the Modification of Diet in Renal Disease equation. Prevalence of eGFR-based renal impairment was estimated for the overall RA population and for two subgroups: patients on advanced therapies (biologic disease-modifying antirheumatic drugs/tofacitinib) and patients stratified based on health plan types. Results Among 128,062 patients with ≥ 2 RA claims, 42,173 had qualifying SCr measurements, 16,197 were on advanced RA therapies, and 4911 had Medicare Advantage or Supplemental plus Part D coverage. For the overall population and the subgroup on advanced therapies, mild renal impairment was observed in 52% and 51%, moderate renal impairment in 9% and 7%, and severe renal impairment in 0.5% and 0.3% of patients, respectively. Moderate and severe renal impairment was more prevalent in the Medicare Advantage/Supplemental plus Part D population compared to the commercial coverage population. Conclusions Approximately 7–10% of commercially insured adult patients in the US with RA had moderate or severe renal impairment. Assessment of renal function is an important consideration for safe treatment.

Introduction Peficitinib, a Janus kinase (JAK) inhibitor, is approved for clinical use in Japan, Korea, and Taiwan, but head-to-head comparisons versus other JAK inhibitors are lacking. We indirectly compared peficitinib, tofacitinib, and baricitinib for rheumatoid arthritis treatment. Methods We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and congress archives up until February 12, 2019, for randomized controlled trials of peficitinib, tofacitinib, and baricitinib. Efficacy (American College of Rheumatology responses, disease activity scores, modified total Sharp score, Simplified Disease Activity Index [SDAI]) and safety outcomes were compared using a Bayesian network meta-analysis. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results. A network meta-regression assessed the impact on outcomes of proportions of patients receiving concomitant methotrexate or of Asian ethnicity. Results The network meta-analysis included 21 randomized controlled trials. At 12 weeks, all evaluable efficacy outcomes were comparable or improved with peficitinib 150 mg and 100 mg once daily, versus baricitinib 2 and 4 mg once daily and tofacitinib 5 mg twice daily. At 24 weeks, efficacy outcomes were comparable or improved for each peficitinib dose versus baricitinib and tofacitinib. Risk of adverse events and serious adverse events at 12 weeks were similar with peficitinib 100 and 150 mg versus baricitinib and tofacitinib. The proportion of patients receiving concomitant methotrexate had no effect on any outcome analyzed, but Asian ethnicity had a positive effect on multiple efficacy outcomes. Conclusions Peficitinib had comparable efficacy versus tofacitinib and baricitinib for reduction in disease activity as measured by SDAI, and for reduction in progression of joint damage as measured radiographically. No notable differences in safety outcomes were observed. Further studies are required to better characterize the impact of ethnicity on the efficacy of JAK inhibitors. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00284-1.

Introduction The objective of this study was to evaluate the cost-effectiveness of initiating treatment with tofacitinib and subsequently incorporating it into a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) treatment sequence and to compare the cost-effectiveness of this sequence with that of continuing csDMARDs alone in patients with active rheumatoid arthritis (RA). Methods A cohort-based Markov model was used to evaluate the cost-effectiveness of two tofacitinib treatment sequences compared with that of continuing the csDMARD treatment sequence over a lifetime. Of the two tofacitinib sequences, the first consisted of initial tofacitinib treatment followed by biologic DMARDs (bDMARDs) and the second consisted of csDMARD treatments followed by tofacitinib. A third treatment sequence, continuing the csDMARD treatment sequence before starting bDMARDs, was used as a comparator. Efficacy was assessed using the American College of Rheumatology (ACR) response rates (ACR 20, ACR 50, and ACR 70) after 6 months, which were converted to changes in the health assessment questionnaire-disability index (HAQ-DI) score. Utility was estimated by mapping from the HAQ-DI score, costs were analyzed from a Korean societal perspective, and outcomes were considered in terms of quality-adjusted life-years (QALYs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. Results The incremental cost-effectiveness ratios over a lifetime for starting with tofacitinib and incorporating tofacitinib into the csDMARD treatment sequence versus continuing csDMARDs only were US$14,537 per QALY and US$7,086 per QALY, respectively. One-way sensitivity analysis and probabilistic sensitivity analysis confirmed the robustness of these results. Conclusion Starting with tofacitinib and incorporating it into a csDMARDs treatment sequence is cost-effective compared to continuing csDMARDs alone in patients with RA.

Introduction This study describes the frequency of prescription claims for drugs that may interact with Janus kinase (JAK) inhibitors among adult patients with rheumatoid arthritis (RA) in a large US claims database. Methods This observational, retrospective, cross-sectional study of the IBM® MarketScan® Research Commercial and the Medicare Supplemental Database included adults (≥ 18 years) with ≥ 2 outpatient claims 30 or more days apart or ≥ 1 inpatient visit claim with an RA diagnosis between January 1, 2013 and March 31, 2017 (the index period). During the study period, from January 1, 2013 to March 31, 2018, strong organic anion transporter (OAT3) inhibitors, strong cytochrome P450 (CYP) 3A4 inhibitors, and moderate or strong CYP3A4 inhibitors in combination with strong CYP2C19 inhibitors, were identified as drugs with potential for drug–drug interactions (DDIs) with JAK inhibitors approved for RA treatment in the US. Descriptive statistics were conducted. Results A total of 152,853 patients met eligibility criteria. Approximately 76% were women and the median age was 57 years. Of these patients

Introduction Upadacitinib and tofacitinib are Janus kinase inhibitors approved for moderate-to-severe rheumatoid arthritis (RA). In the absence of head-to-head trials comparing their effectiveness, this study assessed the efficacy of upadacitinib 15 mg once-daily monotherapy/combination therapy against tofacitinib 5 mg twice-daily combination therapy among patients with RA using matching-adjusted indirect comparisons (MAICs). Methods The first of two MAICs used individual patient data (IPD) from the 14-week SELECT-MONOTHERAPY trial (upadacitinib [n = 217] vs. methotrexate [n = 216]) and published data from the ORAL Standard trial (tofacitinib + methotrexate [n = 204] vs. methotrexate [n = 108]). The second MAIC used IPD from the 26-week SELECT-COMPARE trial (upadacitinib + methotrexate [n = 647] vs. adalimumab + methotrexate [n = 324]) and published data from ORAL Strategy (tofacitinib + methotrexate [n = 376] vs. adalimumab + methotrexate [n = 386]). Data from patients in the upadacitinib trials were re-weighted based on age, sex, race, swollen joint count 66/28, tender joint count 68/28, C-reactive protein (CRP), and patients’ global assessments to match the patient characteristics in tofacitinib trials. After matching, ACR20/50/70 and clinical remission (SDAI[CRP] ≤ 3.3, CDAI ≤ 2.8, DAS28-ESR/CRP

Tofacitinib is approved for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who do not respond adequately or are intolerant to one or more disease-modifying anti-rheumatic drugs. The tofacitinib RA clinical development program included randomized controlled trials of 6–24-month duration and long-term extension studies with > 7061 patients and 22,875 patient-years of exposure. To date, there are no data from other randomized studies in patients with cardiovascular risk factors comparing the long-term safety of a JAK inhibitor versus an anti-TNF. Real-world studies are necessary to complete the body of evidence supporting the effectiveness and safety of a therapeutic agent. In the case of tofacitinib, real-world data derive from health insurance claims databases, registries (US Corrona Registry, Swiss Registry, and others), national pharmacovigilance programs, and hospital databases (case series). The present article provides complete and up-to-date information on the safety profile of tofacitinib in RA, from clinical trials to real-world studies. Tofacitinib has demonstrated a consistent safety profile during up to 9.5 years of experience in randomized controlled trials and long-term extension studies. Real-world evidence has not added new safety issues with respect to those found in the clinical program. In general, the safety profile of tofacitinib is consistent with that of biologic disease-modifying anti-rheumatic drugs, with an increased risk of herpes zoster that seems to be a class effect of Janus kinase inhibitors. The continuous follow-up of therapeutic agents to treat rheumatoid arthritis is needed to adequately establish the safety profile for new mechanisms of action and potential risks associated with their longer term use.

Introduction Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). We report the interim safety, tolerability, and efficacy of tofacitinib in PsA patients in OPAL Balance, a 3-year, open-label, long-term extension study (data cut-off: August 2017; database not locked, data may change). Methods Eligible patients from two phase (P) 3 (P3) tofacitinib PsA studies (OPAL Broaden, NCT01877668; OPAL Beyond, NCT01882439) entered OPAL Balance ≤ 3 months after completing the P3 study or discontinuing for reasons other than study-drug-related adverse events (AEs). Patients received open-label tofacitinib 5 mg twice daily (BID), with adjustments to 10 mg BID permitted post-month (M) 1. Certain concomitant conventional synthetic disease-modifying antirheumatic drugs were allowed. Primary endpoints were incidence/severity of AEs and laboratory abnormalities, and changes from baseline in laboratory parameters (reported up to M36 and M30, respectively). Efficacy (clinical/patient-reported outcomes) was reported through M30. Results A total of 686 patients were treated; at data cut-off, 68.2% remained in the study. Mean (range) treatment duration was 641 (1–1032) days; total treatment duration was 1153.2 patient-years. By M36, 79.6, 13.8, and 8.6% of patients reported AEs, serious AEs, and discontinuations due to AEs, respectively. Five deaths occurred; one within the risk period (incidence rate [IR; patients with events/100 patient-years] 0.1). IRs for AEs of special interest were: all (non-serious and serious) herpes zoster, 1.7; serious infections, 0.9; opportunistic infections, 0.3 (all disseminated/multi-dermatomal herpes zoster); malignancies excluding non-melanoma skin cancer (NMSC), 0.8; NMSC, 1.0; major adverse cardiovascular events, 0.3; pulmonary embolisms, 0.1; and arterial thromboembolisms, 0.4. No patients had deep vein thrombosis. Alanine aminotransferase and aspartate aminotransferase levels were elevated ≥ 3-fold the upper limit of normal in 4.0 and 2.2% of patients, respectively. Changes in laboratory parameters were generally stable over time, although lymphocyte counts decreased slightly. Efficacy was maintained through M30. Conclusions In this interim analysis of OPAL Balance, tofacitinib safety and efficacy in patients with PsA appeared to be consistent with those of the P3 studies. Efficacy was maintained over time. Trial Registration ClinicalTrials.gov identifier: NCT01976364. Electronic Supplementary Material The online version of this article (10.1007/s40744-020-00209-4) contains supplementary material, which is available to authorized users., Plain Language Summary In many countries, tofacitinib is an approved medicine that can be used to treat psoriatic arthritis (PsA). In the study reported here (OPAL Balance), adult patients with PsA took tofacitinib for up to 3 years. We report a planned interim analysis, i.e., an analysis of information collected before the study finished. This early information suggests that the safety of tofacitinib, and how well it improved symptoms and quality of life (efficacy), was similar in this long study as in shorter studies. Information from the finished study will be reported later. OPAL Balance started on 17 February 2014. This interim analysis includes information collected by 31 August 2017. Before joining, patients had finished a 6-month or 12-month tofacitinib study (OPAL Broaden or OPAL Beyond). Patients in OPAL Balance took a 5 mg tofacitinib pill twice a day, but if PsA symptoms did not improve after 1 month, they could take a 10 mg pill twice a day. They could also take other medicines (including methotrexate or corticosteroids). Of the 686 patients who took tofacitinib, 546 (80%) experienced side effects over 3 years. These were considered serious for 95 patients (14%) and caused 59 patients (9%) to leave the study. Five patients died from causes not related to tofacitinib. Known tofacitinib side effects, including shingles (herpes zoster), serious infections (needing hospitalization), infections in patients with weakened immune systems, cancer, heart (cardiovascular) problems, and vein blockages (embolisms), were each reported by fewer than 20 patients. Most blood test results and tofacitinib efficacy were stable over 2.5 years. Electronic Supplementary Material The online version of this article (10.1007/s40744-020-00209-4) contains supplementary material, which is available to authorized users.

Introduction Some patients with rheumatoid arthritis (RA) using tumor necrosis factor inhibitors (TNFi) experience inefficacy or lack of tolerability and hence switch to another TNFi (cycling) or to a therapy with another mode of action (switching). This study examined patient characteristics, prescribing patterns and treatment practice for RA in the United States. Methods Data were from the Adelphi Disease Specific Programme (Q2–Q3 2016). Rheumatologists completed a survey and patient record forms for adult patients with RA who had received ≥ 1 targeted therapy. Patients were grouped by class of first-used targeted therapy, and monotherapy vs. combination therapy. TNFi patients who received ≥ 1 targeted therapy were classified as cyclers or switchers. Univariate analyses compared patient characteristics and physician factors across the analysis groups. Results Overall, 631 patients received ≥ 1 targeted therapy; 535 were prescribed a TNFi as first targeted therapy, 53 a nonTNFi biologic disease-modifying antirheumatic drug (bDMARD), and 43 tofacitinib. Of 577 patients with known conventional synthetic (cs) DMARD status, 18.7% were prescribed monotherapy and 81.3% combination therapy. Combination therapy patients received significantly more concomitant medications prior to initiation of first targeted therapy than monotherapy patients (P

Introduction No published studies exist comparing the effectiveness of tofacitinib with other advanced therapies for the treatment of rheumatoid arthritis (RA) in real-world clinical practice. Here, we report differences in effectiveness of tofacitinib compared with standard of care, tumor necrosis factor inhibitors (TNFi), with or without concomitant methotrexate (MTX), using US Corrona registry data. Methods This observational cohort study included RA patients receiving tofacitinib (from 6 November 2012; N = 558) or TNFi (from 1 November 2001; N = 8014) with or without MTX until 31 July 2016. Efficacy outcomes at 6 months included modified American College of Rheumatology 20% responses, Clinical Disease Activity Index (CDAI) and Pain. Outcomes were compared between patients receiving TNFi and tofacitinib with or without MTX and by line of therapy. Outcomes within therapy lines were compared using propensity-score matching; between-group differences were estimated using mixed-effects regression models. Results Patients receiving tofacitinib had longer RA duration and a greater proportion had previously received biologics than those receiving TNFi; other baseline characteristics were comparable. In patients receiving second- and third-line TNFi therapy, CDAI low disease activity/remission response rates were significantly better with concomitant MTX. Too few patients received tofacitinib as second line for meaningful assessment. No significant differences were observed in outcomes between tofacitinib as monotherapy and tofacitinib with concomitant MTX. Conclusions In clinical practice, TNFi efficacy is improved with concomitant MTX in the second and third line. In the third/fourth line, patients are likely to achieve similar efficacy with tofacitinib monotherapy, or TNFi or tofacitinib in combination with MTX. Funding Pfizer Inc Electronic supplementary material The online version of this article (10.1007/s40744-019-00177-4) contains supplementary material, which is available to authorized users.

Introduction In 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. Methods Data 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. Results Across 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. Conclusions In Australian patients with RA, tofacitinib therapy demonstrated sustained efficacy and consistent safety over ≥ 60 months’ treatment. Funding Pfizer Inc. Trial registration numbers (all ClinicalTrials.gov) NCT00960440; NCT00847613; NCT00856544; NCT00853385; NCT00413699. Electronic supplementary material The online version of this article (10.1007/s40744-018-0118-2) contains supplementary material, which is available to authorized users.

Post-marketing surveillance (PMS) is an integral part of monitoring adverse events (AEs) following approval of new drugs. Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). An analysis of PMS reports was conducted to evaluate the safety of tofacitinib in a post-marketing setting. Worldwide tofacitinib PMS data received in the Pfizer safety database from November 6, 2012 (first marketing authorization of tofacitinib) to November 5, 2015 were analyzed. Serious AEs (SAEs) of interest were reviewed and reporting rates (RRs) were calculated by dividing the number of SAEs by the estimated 100 patient-years of exposure. Patient exposure was calculated based on estimated worldwide sales and an estimated daily regimen of tofacitinib 5 mg twice daily. During the 3-year reporting period, worldwide post-marketing exposure to tofacitinib since approval was estimated to be 34,223 patient-years. In total, 9291 case reports (82.9% non-serious) were received and 25,417 AEs, 102 fatal cases, and 4352 SAEs were reported. The RRs (per 100 patient-years) for SAEs of interest by Medical Dictionary for Regulatory Activities System Organ Class were 2.57 for infections, 0.91 for gastrointestinal disorders, 0.60 for respiratory disorders, 0.45 for neoplasms, 0.43 for cardiac disorders, and 0.12 for hepatobiliary disorders. Although there are limitations to these data, no new safety risks were revealed in this real-world setting compared with the safety profile identified in the tofacitinib RA clinical development program. Any risks identified through the tofacitinib development program and PMS will continue to be monitored through pharmacovigilance surveillance. Pfizer Inc.