In this review, we summarize the key characteristics of LTα and the most recent findings on the role of LTα in RA.

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Considered costs and discontinuation and switching event rates were lowest with ETN versus IFX, ADA, or TCZ used as the first-line biologic. Despite limitations, these findings imply clinical cost-reductive benefits of ETN as the first-line biologic treatment option for rheumatoid arthritis in Japan.

Long-term ETN treatment safety and effectiveness were sustained over 3 and 2 years, respectively.

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 (N¼ 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. ARTICLE HISTORY

Background Tumour necrosis factor inhibitors (TNFi's) such as etanercept (ETN), adalimumab (ADA) and infliximab (IFX) have led to dramatic improvements in the treatment of rheumatoid arthritis (RA), but their impact on medical expenditures remains a concern. It is therefore important to aim for sustained clinical benefits through persistent treatment whilst minimizing the impact of the drug cost on medical expenditures based on initiating the most cost-effective RA treatment. Objectives The aim of this study is to evaluate retention rates across three commonly used TNFi's and compare associated cumulative direct biologics and medical costs using a nationwide Japanese claims database containing about two million subscribers from the health insurance society provided by the Japan Medical Data Center Co., Ltd. Methods Subjects of this study were patients with rheumatoid arthritis (ICD10 code: M058, M059, M060, M068, M069) prescribed ETN, IFX or ADA as the first biologics between January 2005 and March 2013. Annual average costs of the initial biologics per patient were calculated between 2005 and 2012. Next, the retention rates of ETN, IFX and ADA were examined using Kaplan-Meier survival analysis. Lastly, the cumulative biologics cost including second (or subsequent) biologics (tocilizumab, abatacept, golimumab, certolizumab and three TNFi's) as well as the total medical costs were compared in the year following the initial prescription of ETN, IFX or ADA (The approved dose in Japan for ETN: 10 to 25 mg twice weekly or 25 to 50 mg per week, IFX: 3 to 10mg/kg every 4 to 8 weeks, ADA: 40 to 80mg every 2 weeks). Results 524 RA patients initiating selected biologic therapy were identified for this analysis. 238, 217 and 69 patients were prescribed ETN, IFX, ADA as the first biologic, respectively. The annual cost for ETN per patient was about $10,000 in 2007 and $7,200 in 2012. The annual cost for IFX per patient was about $13,000 in 2007, but after approval of dose escalation in 2009, it was $16,000 in 2012. The retention rate of each TNFi at 36 months was 51.4%, 42.0% and 24.2% for ETN, IFX and ADA, respectively (ETN vs. IFX, p=0.053; ETN vs.ADA, p=0.004, Log-rank test) (Fig.1). The average cumulative annual cost of biologics for patients initiated with ETN, IFX and ADA as the first biologics treatment was about $12,000, $18,000 and $16,000, respectively (ETNvs IFX, p<0.001; ETN vs. ADA, p<0.001, IFX vs. ADA, p=0.751, Steel-Dwass test) (Fig.2). The average total annual medical cost with ETN, IFX and ADA as the first biologics treatment were $19,000, $26,000 and $23,000, respectively (ETN vs IFX, p<0.001, ETN vs. ADA, p<0.001, IFX vs. ADA, p=0.826, Steel-Dwass test). Conclusions The retention rate of ETN as the first biologics treatment was the highest among three TNFi's while cumulative annual cost of biologics and total medical cost following the initial treatment of patients with ETN was significantly lower than comparators. Therefore, ETN may be considered a more cost-effective option to other TNFi's a...

Objectives: To confirm the safety and effectiveness of high-dose (>8 mg/week) methotrexate (MTX) for the treatment of rheumatoid arthritis in Japan. Methods: A postmarketing surveillance program enrolled Japanese patients with rheumatoid arthritis starting on high-dose MTX followed up for either 24-or 52-weeks. Analyses for safety, risk factors affecting safety, and effectiveness were conducted. Results: The safety/effectiveness analysis sets included 2838/2779 and 335/326 patients in the 24weeks and 52-weeks follow-up groups, respectively. Incidence rates of adverse drug reactions (ADRs) and serious ADRs were 21.42% and 1.66% in the 24-weeks, and 35.52% and 2.69% in the 52-weeks groups, respectively. The Disease Activity Score in 28 Joints (DAS28) was significantly decreased as early as four weeks from the start of high-dose MTX; after 24-weeks (4.09-3.21) and 52-weeks of treatment (3.91-2.80; both p < .001). In a majority of patients at baseline who had high-to-moderate disease activity, the remission rate (defined as DAS < 2.6) increased three-fold from 10.6% (baseline) to 33.0% (24-weeks) compared to patients with low disease activity whose remission rate increased two-fold from 24.0% (baseline) to 53.6% (24-weeks). Conclusions: High-dose MTX was well tolerated in Japanese patients, resulted in improved disease control, and can be considered a step forward in achieving treat-to-target goals.

ObjectivesThe aim of this study was to characterize the treatment patterns of patients with RA treated with biologics and evaluate the direct biologics cost and medical cost using Japanese claims data provided by Japan Medical Data Center Co Ltd.MethodsPatients with RA (defined by ICD10 code: M058, M059, M060, M068, M069), aged ≥16 to <75 treated with etanercept (ETN), infliximab (IFX), adalimumab (ADA), and toclizumab (TCZ) as first biologic, between Jan 2005 and Mar 2013 were included. One-, two- and three-year cumulative total medical cost following initial prescription was compared between each treatment group. Discontinuation event rates in each group were estimated using Kaplan-Meier survival analysis. Dose of each first biologic treatment until discontinuation was analyzed to calculate relative dose intensity (RDI) which shows (Actual cumulative dose)/(Expected dose when initial dose was continued until discontinuation).ResultsA total of 603 patients were identified for longitudinal analysis, with 41% (n=246) initiating ETN, 36% (n=217) initiating IFX, 11% (n=69) initiating ADA and 12% (n=71) initiating TCZ. The total medical costs from the initial prescription in ETN, IFX, ADA and TCZ groups were approximately $19,000, $26,000, $23,000 and $24,000 in one year, and $50,000, $65,000, $52,000 and $71,000 in three years, respectively (ETN: IFX p=0.004, ETN: ADA p=0.988, ETN: TCZ p=0.027, ADA: IFX p=0.417, ADA: TCZ p=0.845, IFX: TCZ p=0.198) (Fig 1). The discontinuation event rate at 36th month was 46.4%, 58.0%, 75.8% and 59.3% in ETN, IFX, ADA and TCZ groups, respectively (ETN: IFX p=0.007, ETN: ADA p<0.001, ETN: TCZ p=0.037, ADA: IFX p=0.147, ADA: TCZ p=0.767, IFX: TCZ p=0.385) (Fig 2). The mean RDIs of ETN25mg, ETN50mg, IFX, ADA and TCZ groups were 1.08 (95%CI: 1.00-1.15), 0.89 (95%CI: 0.85-0.93), 1.21 (95%CI: 1.16-1.27), 0.99 (95%CI: 0.92-1.06), and 0.96 (95%CI: 0.84-1.08), respectively (Fig 3).ConclusionsThe discontinuation rate was lowest in the ETN group, which indicates sustained treatment and good adherence to the therapy. RDI analysis of IFX showed a 1.21 times higher than expected dose. This high RDI value was due to the dose escalation from initial phase of treatment and may be one of the reasons for the higher cost of IFX observed in our study. These results support the relation between adherence and medical cost reduction in RA patients previously reported.1ReferencesClark et al. The Relationship Between Adherence and Health Care Cost among Patients with Rheumatoid Arthritis: A Retrospective Case Comparison Study. International Society for Pharmacoeconomics and Outcomes Research. 19th Annual International Meeting 2014Disclosure of InterestN. Sugiyama Employee of: Pfizer, T. Murata Consultant for: Employee of CRECON who performed the analyses and were funded by Pfizer, Employee of: Employee of CRECON who performed the analyses and were funded by Pfizer, Y. Morishima Employee of: Pfizer, Y. Fukuma Employee of: Pfizer, Y. Shibasaki Employee of: Pfizer, L. Marshall Employee of: Pfizer