Factors contributing to the improvement in J-HAQ after 3 years of treatment with abatacept in biologic-naïve rheumatoid arthritis patients: Interim results of a long-term, observational, multicentre study in Japan (ORIGAMI).

OBJECTIVES: We investigated the long-term effectiveness, safety, and factors affecting Japanese Health Assessment Questionnaire (J-HAQ) improvement during abatacept treatment in Japanese rheumatoid arthritis (RA) patients. METHODS: The ORIGAMI study is an ongoing observational study of biologic-naïve RA patients with moderate disease activity treated with subcutaneous abatacept (125 mg, once-weekly). Patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry as an historical, weighted control group. The primary endpoint for this interim analysis was the proportion of patients with J-HAQ remission (score ≤0.5) at 3 years. RESULTS: Among 279 abatacept-treated and 220 csDMARD-treated patients, J-HAQ remission was achieved at 3 years in 40.5% (95% confidence interval [CI] 34.7%-46.2%) and 28.9% (95% CI 9.9%-47.8%), respectively. Age, RA duration <1 year, baseline J-HAQ score, and Simplified Disease Activity Index remission at 6 months were associated with 3-year J-HAQ remission in the abatacept group. Overall, 24/298 patients (8.1%; safety analysis set) experienced serious adverse drug reactions with an incidence of 5.3 per 100 person-years. CONCLUSIONS: This study confirmed the 3-year effectiveness and safety, and revealed potential factors associated with J-HAQ remission in biologic-naïve RA patients treated with abatacept in real-world clinical practice.

Effectiveness and safety of subcutaneous abatacept in biologic-naïve RA patients at Week 52: A Japanese multicentre investigational study (ORIGAMI study).

OBJECTIVES: To evaluate the effectiveness and safety of abatacept over 52 weeks in biologic-naïve rheumatoid arthritis (RA) patients with moderate disease activity in the prospective, 5-year, observational study (ORIGAMI study) in Japan. METHODS: Abatacept (125 mg) was administered subcutaneously once a week. Clinical outcomes included Simplified Disease Activity Index (SDAI) remission at Week 52 (primary endpoint), Japanese Health Assessment Questionnaire (J-HAQ), EuroQol 5-Dimension Questionnaire (EQ-5D), treatment retention, and safety. The results were compared with those of conventional synthetic disease-modifying antirheumatic drug (csDMARD) controls from the ongoing Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry. RESULTS: Overall, 325 patients were enrolled, with a mean age of 66.9 ± 12.7 years. The proportion of patients achieving SDAI remission (≤3.3) at Week 52 was 18.9% (95% CI: 14.3-23.6) and low disease activity (≤11) was 53.3% (95% CI: 47.4-59.1). A significant improvement was observed in J-HAQ and EQ-5D over 52 weeks in both the abatacept and csDMARD groups. The probability of abatacept treatment retention at Week 52 was 69.9% (95% CI: 64.7-75.5). Adverse events and serious adverse events were reported in 50.0% and 12.1% of patients, respectively. CONCLUSIONS: Abatacept significantly improved disease activity, physical disability, and quality of life for up to 52 weeks in RA patients in a real-world setting.

Risk of serious infection, malignancy, or death in Japanese rheumatoid arthritis patients treated with a combination of abatacept and tacrolimus: a retrospective cohort study.

To evaluate whether combinatorial use of abatacept (ABT) and tacrolimus (Tac) increases the risk of adverse events compared to their individual use in Japanese rheumatoid arthritis (RA) patients. We conducted a retrospective cohort study of RA patients using the Japanese multicenter database and analyzed the data of RA patients registered from April 2010 to March 2019 by comparing three treatment groups who received Tac, ABT, or a combination of both. We included patients who had initiated treatment with ABT or Tac and excluded patients who used tumor necrosis factor inhibitors, IL-6 inhibitors, and Jak inhibitors in the first year of our study. The primary outcome was the occurrence of adverse events such as infections that required hospitalization, newly diagnosed malignancy, or death from any cause after initiation of ABT or Tac. Of the 27,032 RA patients in the registry, 2009 patients were included. The Tac, ABT, and combination groups consisted of 1328, 563, and 118 patients, respectively. Primary outcome occurred in 149 (13.4%), 62 (13.5%), and 14 (13.9%) patients of the Tac, ABT, and combination groups, respectively. The incidence of adverse events between groups was not significantly different (p = 0.638). A Cox regression analysis which was adjusted for potential confounders such as age, disease activity, and concomitant use of prednisolone revealed no significant differences between groups. The combinatorial use of ABT and Tac, or ABT alone does not increase the risk of adverse events when compared to the use of Tac alone in RA patients in Japan. Key Points • This study included Japanese rheumatoid arthritis data and found that there was no significant risk when patients were treated with a combination of Tac and ABT or each drug alone.

Differences in clinical manifestations, treatment, and concordance rates with two major sets of criteria for Behçet's syndrome for patients in the US and Japan: data from a large, three-center cohort study.

OBJECTIVE: To compare Behçet's syndrome (BS) cohorts from the US and Japan in terms of rates of concordance with the International Study Group (ISG) criteria and Japanese criteria, disease manifestations, and treatment. METHODS: All BS patients seen at the NYU Hospital for Joint Diseases in the US and the Kameda Medical Center and St. Luke's International Hospital in Japan between 2003 and 2010 were included. Diagnosis of BS was made on the basis of clinical manifestations and the clinical decisions of experienced specialists familiar with BS. We classified the patients into complete and incomplete types based on their symptoms; both complete or incomplete types were assumed to fulfil the Japanese criteria. RESULTS: A total of 769 patients (US n = 634, Japan n = 135) were reviewed. 61.5 % in the US and 63.7 % in Japan fulfilled the ISG criteria. Similarly, there was no difference in the proportions of US and Japanese patients who fulfilled the Japanese criteria. Japanese patients were less likely to be female and to have genital ulcers, but were more likely to have epididymitis and pulmonary disease. Significantly more patients were treated with colchicine, sulfasalazine/mesalazine, and NSAIDs in Japan, while significantly more patients in the US received first-line immunosuppressants. CONCLUSIONS: The concordance rates for ISG and Japanese criteria fulfillment in the US and Japan were not significantly different. These findings could help to clarify regional differences in the diagnostic and clinical features of BS.

An observational study of tocilizumab and TNF-α inhibitor use in a Japanese community hospital: different remission rates, similar drug survival and safety.

OBJECTIVE: To assess the effectiveness, drug survival and safety of tocilizumab compared with TNF-α inhibitors in clinical practice. METHODS: Patients in the Cohort of Arthritis Biologic Users at Kameda Institute (CABUKI) registry who were on biologics during July 2003 to October 2010 were included. Remission rates at 6 months, Kaplan-Meier drug survival estimates and serious adverse event (SAE) rates were compared. RESULTS: A total of 247 RA patients were analysed. For first-line biologic users, the 6-month 28-joint DAS (DAS-28)-ESR remission rates were 66.7% for tocilizumab vs 25.8% for TNF inhibitors (P < 0.001, Fisher's exact test). This advantage disappeared with the application of the newly suggested Boolean remission criterion for clinical trials: 0% for tocilizumab vs 8.2% for TNF inhibitors (P = 0.367, Fisher's exact test). Tocilizumab users in DAS-28-ESR remission had lower mean ESR (3.9 mm/h for tocilizumab vs 7.9 mm/h for TNF inhibitors, P = 0.026, t-test) and higher mean swollen joint count (2.6 for tocilizumab vs 1.3 for TNF inhibitors, P = 0.036, t-test), thus failing to meet the more stringent Boolean criteria. First- and second-line tocilizumab users showed similar drug survival and SAE rates compared with TNF inhibitor users. CONCLUSION: Tocilizumab had drug survival and safety profiles similar to those of TNF inhibitors in this Japanese single-centre registry. Tocilizumab was superior to TNF inhibitors when compared at 6 months by DAS-28-ESR remission. However, the newly suggested Boolean criteria are more appropriate measures of effectiveness as DAS-28-ESR remission by tocilizumab was mainly due to very low ESR in our study population.