Treatment Of Rheumatoid Arthritis In Japan Research Articles

Japan College ofRheumatology guidance forthe use ofmethotrexate inpatients with rheumatoid arthritis: Secondary publication.

Methotrexate (MTX), the anchor drug in the current treatment strategy for rheumatoid arthritis (RA), was first approved for the treatment of RA in Japan in 1999 at a recommended dose of 6-8 mg/week. The approved maximum dose of MTX has been 16 mg/week since February 2011 when MTX was approved as a first-line drug in the treatment of RA. Recent evidence of MTX-polyglutamate concentration in the red blood cells of Japanese patients with RA justifies the current daily use of MTX in Japan. Additionally, after a nationwide clinical trial, a subcutaneous MTX injection formula (7.5-15 mg/week) was approved for RA treatment in September 2022. Therefore, in March 2023, a subcommittee of the Japan College of Rheumatology updated the guidance (formerly 'guidelines') for the use of MTX in Japanese patients with RA. This article, an abridged English translation summarizing the 2023 update of the Japan College of Rheumatology guidance for the use of MTX and management of patients with RA, will be helpful to both Japanese and global rheumatology communities.

A retrospective, longitudinal study of rheumatoid arthritis treatment patterns with Janus kinase inhibitors and other disease-modifying antirheumatic drugs in Japan.

There is limited information on the clinical use of Janus kinase inhibitors (JAKis) for rheumatoid arthritis treatment in Japan. The aim of this study was to identify disease-modifying antirheumatic drug (DMARD) treatment patterns in Japan. This retrospective, longitudinal study extracted data from the Japan Medical Data Center database. Patients with rheumatoid arthritis diagnosis were enrolled 2016-19, during which patients had a first prescription of a major DMARD, split into six mutually exclusive classes: methotrexate (MTX); other conventional synthetic DMARDs; tumour necrosis factor alpha inhibitors; cytotoxic T-lymphocyte-associated antigen-4-immunoglobulin; anti-interleukin-6 receptor therapies; and JAKis. The primary objective was to describe DMARD treatment patterns, especially for JAKis. Overall, 10,399 patients were included in the analysis. The most common treatments were MTX, other conventional synthetic DMARDs, and tumour necrosis factor alpha inhibitors. The total number of JAKi prescriptions increased approximately 8-fold during 2016-19. Most (61.1%) patients who received JAKis had prior MTX or tumour necrosis factor alpha inhibitor treatment. The duration of JAKi treatment was longer than for biologics and other conventional synthetic DMARDs and comparable to that of MTX. The sequence of drug class prescriptions for rheumatoid arthritis in Japan during 2016-19 followed clinical guidelines. Over this period, JAKis were increasingly used as a second-line treatment following MTX.

Current status of shared decision making for rheumatoid arthritis treatment in Japan: a web-based survey on physicians and patients

Objective To assess the current status of shared decision making (SDM) in rheumatoid arthritis (RA) clinical practice in Japan from the perspectives of physicians and patients. Methods A web-based survey was conducted to recruit patients with RA who were prescribed, for the first time, a conventional synthetic disease-modifying antirheumatic drug (csDMARD) or a biological drug/Janus kinase (JAK) inhibitor, and physicians who prescribed these treatments to patients with RA. The SDM Questionnaire-Physician version (SDM-Q-Doc) and the 9-item SDM Questionnaire (SDM-Q-9) were used to assess the SDM levels of physicians and patients, respectively. The scale ranged from 0 to 100, and higher scores indicated better SDM status. Results The responses from 107 physicians who treat patients with RA, 107 patients prescribed a csDMARD, and 110 patients prescribed a biological drug/JAK inhibitor were collected. The mean SDM score for SDM-Q-Doc was 74.5 when physicians decided to prescribe a csDMARD and 77.2 when they decided to prescribe a biological drug/JAK inhibitor. However, the mean SDM score for SDM-Q-9 was 62.3 when patients were prescribed csDMARDs and 72.6 when they were prescribed biological drugs/JAK inhibitors. Conclusions The results showed differences in SDM level between patients and physicians and, from the patient perspective, between treatment types.

Geographic variations in rheumatoid arthritis treatment in Japan: A nationwide retrospective study using the national database of health insurance claims and specific health checkups of Japan.

To characterize the treatments for rheumatoid arthritis (RA) among institution types and prefectures in Japan. Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan in the 2017 fiscal year, we investigated disease-modifying antirheumatic drug (DMARD) and oral corticosteroid prescription trends across 825 thousand RA patients. These data were compared between specialized and non-specialized institutions and by prefecture. RA specialized institutions (SIs) were defined as either institutions registered in the rheumatology training program at the Japan College of Rheumatology or institutions where board-certified rheumatologists were employed. The overall percentage of patients who never visited an SI was 31.8% and increased with age (16-29 years old = 15.6%; ≥80 years = 42.8%). In twelve prefectures (25.5%), the proportions of patients who never visited an SI were at least 10% higher than the overall average. The proportions of patients who only visited SIs and were prescribed methotrexate and biological DMARDs were ranged from 51.9-72.9% and 19.5-33.2%, respectively. However, those of patients who had never visited an SI and were prescribed those medications were 44.0-71.6% and 7.2-28.0%, respectively. This is the first study evaluating the trends in RA treatments by prefecture and institution specialty by using the NDB Japan. Opportunities of patients with RA for visiting SI was unevenly distributed in Japan, affecting some aspects of treatment provided.

Japan College of Rheumatology guideline for the use of methotrexate in patients with rheumatoid arthritis

Methotrexate (MTX), the anchor drug in the current treatment strategy for rheumatoid arthritis (RA), was first approved for treatment of RA in Japan in 1999 at the recommended dose of 6–8 mg/week; it was approved as first-line drug with the maximum dose of 16 mg/week in February 2011. However, more than half of Japanese patients with RA are unable to tolerate a dose of 16 mg/week of MTX. Moreover, some serious adverse events during the treatment with MTX, such as pneumocystis pneumonia (PCP) and lymphoproliferative disorders (LPD) have been observed much more frequently in Japan than in other countries. Therefore, this article, an abridged English translation summarizing the 2016 update of the Japan College of Rheumatology (JCR) guideline for the use of MTX in Japanese patients with RA, is not intended to be valid for global use; however, it is helpful for the Japanese community of rheumatology and its understanding might be useful to the global community of rheumatology.

Pharmaceutical pricing in Japan: market evidence for rheumatoid arthritis treatment

ABSTRACTBackground: Drug price setting is one of the key challenges faced by the Japanese health care system. This study aims to identify the determinants of drug price in Japan using the example of the rheumatoid arthritis (RA) treatment market.Research design and methods: In order to compare prices across different products, we calculated prices per defined daily dose using WHO methodology. Price determinants were calculated both at launch and over time using IMS quarterly data on medicines approved for RA treatment in Japan from 2012 to 2015. Pharmaceutical pricing was modeled as a function of clinical and economic variables using regression analysis.Results: For prices at the launch we found that differences in efficacy are not reflected in price differentials. We also report that the number of products within a molecule class had a negative effect on prices while originator drugs maintained higher prices.Conclusion: Although the existing pricing rules in Japan are very comprehensive they do not necessarily capture differences in product characteristics. The findings here support the notion that competitive forces are weak in highly regulated markets such as Japan.

Subcutaneous formulation of tocilizumab for treatment of rheumatoid arthritis.

Tocilizumab (TCZ) is a humanized monoclonal antibody against the IL-6 receptor that is indicated for the treatment of rheumatoid arthritis (RA), juvenile idiopathic arthritis and Castleman's disease. TCZ was developed as an intravenous (IV) formulation and approved for RA treatment in Japan (2008), the EU (2009) and the USA (2010). Recently, a subcutaneous (SC) formulation of TCZ was developed and approved for RA treatment. Efficacy and safety of TCZ-SC were reported through three randomized trials: MUSASHI, SUMMACTA and BREVACTA. Clinical efficacy and overall safety of TCZ-SC was comparable to that of TCZ-IV. However TCZ-SC, which is provided in a fixed dose, the efficacy was affected by patient weight. The frequencies of injection site reactions and anti-TCZ antibodies were increased with TCZ-SC compared with TCZ-IV, although differences were minimal and at a negligible level for daily clinical practice. This review highlights the potential of TCZ-SC in RA treatment.

AB1364 Death analysis of 144 rheumatoid arthritis patients over the last 24 years

BackgroundLife expectancy for rheumatoid arthritis (RA) patients is 10 years less than that for other adults. However, there have been major pharmacotherapeutic and surgical advances in the treatment of RA...

Current treatments of rheumatoid arthritis: from the ‘NinJa’ registry

In this review, recent changes in both treatments and outcomes of rheumatoid arthritis (RA) in Japan were analyzed by viewing the National Database of Rheumatic Diseases by iR-net, one of the largest clinical databases for RA patients in Japan. Regarding drug therapy, the use of methotrexate has been continuously increasing and has established a place as an anchor drug in the treatment of RA among other nonbiologic disease-modifying antirheumatic drugs; however, the dosage used is still significantly less compared with that of western countries. In addition to methotrexate, the use of tacrolimus has increased gradually. The most prominent observed change is a rapid increase in the use of biologics, which rose to stardom in the treatment of RA in Japan and western countries. These changes in drug therapy could allow us to control RA disease activity more tightly. In line with this, the outcomes of patients with RA in Japan have been improving continuously, both clinically and functionally. Subsequently, the use of both NSAIDs and corticosteroids has decreased. In addition, overall rates of joint operations related to RA have also decreased; in particular, a significant decrease was noticed in the incidence of joint replacement and synovectomy. Overall, the trends in treatments and subsequent outcomes for RA in Japan have exactly followed those seen in western countries.

Safety and Efficacy of Various Dosages of Ocrelizumab in Japanese Patients with Rheumatoid Arthritis with an Inadequate Response to Methotrexate Therapy: A Placebo-controlled Double-blind Parallel-group Study

To evaluate the safety and efficacy of ocrelizumab (OCR) in Japanese patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). RA patients with an inadequate response to MTX 6-8 mg/week received an infusion of 50, 200, or 500 mg OCR or placebo on Days 1 and 15 and were observed for 24 weeks. The double-blind period was prematurely terminated because of a possible risk for serious infection from OCR. A total of 152 patients were randomized into the study. The incidence of infection was 37.7% (43/114) in the OCR groups combined, compared to 18.9% (7/37) in the placebo group. Serious infections occurred in 7 patients in the OCR groups combined; there were no serious infections in the placebo group. Among the serious infections, Pneumocystis jirovecii pneumonia occurred in 2 patients in the OCR 200 mg group. The American College of Rheumatology 20% response rates at Week 24 (the primary endpoint) of the OCR 50, 200, and 500 mg groups were 54.1% (p = 0.0080), 55.6% (p = 0.0056), and 47.2% (p = 0.044), respectively, all significantly higher than that of the placebo group (25.0%). These results suggest inappropriate benefit-risk balance of OCR in this patient population. Because rituximab is not approved for treatment of RA in Japan, it will be necessary to investigate safety and efficacy of other anti-B cell therapies in Japanese patients with RA. (ClinicalTrials.gov NCT00779220).

The efficacy and safety of reinstitution of tocilizumab in patients with relapsed active rheumatoid arthritis after long-term withdrawal of tocilizumab

We have evaluated the efficacy and safety of tocilizumab (TCZ) re-administration in patients with active rheumatoid arthritis (RA) who had previously received TCZ treatment for about 31 months. Four patients whose RA had been well-controlled with 8 mg/kg TCZ treatment every 4 weeks and had withdrawn from the treatment were enrolled. They resumed TCZ treatment after TCZ was authorized for RA treatment in Japan. Disease activity was assessed by the Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR), and synovitis in the wrists and elbows was measured by ultrasonography at baseline and during follow-up. The mean DAS28-ESR was 6.32 before the first TCZ infusion. After fewer than 20 months of initial TCZ treatment, the mean DAS28-ESR decreased to 1.87. However, after withdrawal of TCZ treatment, the disease activity could not be sufficiently controlled with conventional disease-modifying antirheumatic drugs or biologic agents. The maximum interval between TCZ treatments was approximately 34 months. Following reinstatement of the TCZ treatment, within 12 months the mean DAS28-ESR improved from 5.21 to 2.87, with the synovitis in the wrists and elbow joints also showing great improvement. These findings demonstrate that TCZ retreatment in active RA patients who had relapsed after long-term discontinuation of TCZ treatment led to an improvement in the signs and symptoms of RA and in synovitis without any severe adverse events.

The efficacy and safety of reinstitution of tocilizumab in patients with relapsed active rheumatoid arthritis after long-term withdrawal of tocilizumab

We have evaluated the efficacy and safety of tocilizumab (TCZ) re-administration in patients with active rheumatoid arthritis (RA) who had previously received TCZ treatment for about 31months. Four patients whose RA had been well-controlled with 8mg/kg TCZ treatment every 4weeks and had withdrawn from the treatment were enrolled. They resumed TCZ treatment after TCZ was authorized for RA treatment in Japan. Disease activity was assessed by the Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR), and synovitis in the wrists and elbows was measured by ultrasonography at baseline and during follow-up. The mean DAS28-ESR was 6.32 before the first TCZ infusion. After fewer than 20months of initial TCZ treatment, the mean DAS28-ESR decreased to 1.87. However, after withdrawal of TCZ treatment, the disease activity could not be sufficiently controlled with conventional disease-modifying antirheumatic drugs or biologic agents. The maximum interval between TCZ treatments was approximately 34months. Following reinstatement of the TCZ treatment, within 12 months the mean DAS28-ESR improved from 5.21 to 2.87, with the synovitis in the wrists and elbow joints also showing great improvement. These findings demonstrate that TCZ retreatment in active RA patients who had relapsed after long-term discontinuation of TCZ treatment led to an improvement in the signs and symptoms of RA and in synovitis without any severe adverse events.

Safety and effectiveness responses to etanercept for rheumatoid arthritis in Japan: a sub-analysis of a post-marketing surveillance study focusing on the duration of rheumatoid arthritis

The aim is to investigate the relationship of duration of rheumatoid arthritis (RA) with safety and effectiveness of etanercept (ETN) in Japan. Post-marketing surveillance data for 7,099 patients treated with ETN were analyzed. Baseline characteristics, treatment effectiveness, incidence of adverse events (AEs), and serious AEs (SAEs) in relation to duration of RA were studied. At baseline, patients with RA for longer duration were older, weighed less, had more comorbidities, allergies, and corticosteroid use, but smoked less and had less morning stiffness. By 2–5 years with RA, more than half of the patients had advanced to Steinbrocker radiographic stage III or IV. Methotrexate (MTX) was the most commonly used pre-treatment disease-modifying antirheumatic drug; however, concomitant MTX use and its dose were lower among patients with longer duration of RA. Remission rates (26.6%) were greatest among patients having RA for <2 years. Less AEs and SAEs were observed among patients with shorter duration of RA. These results suggest that RA treatment in Japan in the era pre-biologics may not have been adequate to control disease activity and prevent joint destruction. Patients with shorter duration of RA may have better physical status which allows the opportunity to treat more intensively putting a higher percentage of patients in remission and possibly decreasing exposure to SAEs.

Cancer therapy finds a solid target

<h3>Objective.</h3> To evaluate the safety and efficacy of ocrelizumab (OCR) in Japanese patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). <h3>Methods.</h3> RA patients with an inadequate response to MTX 6–8 mg/week received an infusion of 50, 200, or 500 mg OCR or placebo on Days 1 and 15 and were observed for 24 weeks. The double-blind period was prematurely terminated because of a possible risk for serious infection from OCR. <h3>Results.</h3> A total of 152 patients were randomized into the study. The incidence of infection was 37.7% (43/114) in the OCR groups combined, compared to 18.9% (7/37) in the placebo group. Serious infections occurred in 7 patients in the OCR groups combined; there were no serious infections in the placebo group. Among the serious infections, <i>Pneumocystis jirovecii</i> pneumonia occurred in 2 patients in the OCR 200 mg group. The American College of Rheumatology 20% response rates at Week 24 (the primary endpoint) of the OCR 50, 200, and 500 mg groups were 54.1% (p = 0.0080), 55.6% (p = 0.0056), and 47.2% (p = 0.044), respectively, all significantly higher than that of the placebo group (25.0%). <h3>Conclusion.</h3> These results suggest inappropriate benefit-risk balance of OCR in this patient population. Because rituximab is not approved for treatment of RA in Japan, it will be necessary to investigate safety and efficacy of other anti-B cell therapies in Japanese patients with RA. (ClinicalTrials.govNCT00779220).