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Background: The administration of Janus kinase inhibitors as well as biological disease-modifying anti-rheumatic drugs has dramatically improved the clinical outcomes of patients with rheumatoid arthritis (RA). Previous trials have shown that upadacitinib, a Janus kinase inhibitor, can effectively improve disease activity and prevent progression of joint destruction in RA patients with inadequate responses to methotrexate (MTX). It remains unclear whether reduced disease activity can be maintained after discontinuation of MTX in patients treated with upadacitinib plus MTX. Thus, the aim of this study is to evaluate changes in disease activity after administration of upadacitinib plus MTX in RA patients who failed to achieve an adequate response to MTX and to determine whether clinical relapse can be avoided after discontinuation of MTX in those who achieved clinical remission. Methods/design: The proposed study is an interventional, multicenter, open-label, single-arm clinical trial with a 48-week follow-up. The cohort will include 155 RA patients with at least moderate disease activity during treatment with MTX. Patients will receive upadacitinib and MTX will be discontinued for those who achieve clinical remission. Disease activity will be evaluated longitudinally by measuring clinical disease activity indices and with musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who sustain a disease activity score-28- C reactive protein score of ≤3.2 from week 24 to 48 after a disease activity score-28- C reactive protein score of <2.6 at week 24. Important secondary endpoints are changes from baseline MSUS scores. Serum levels of multiple biomarkers, including cytokines and chemokines, will be comprehensively analyzed. Discussion: The study results are expected to show the clinical benefit of the discontinuation of MTX after achieving clinical remission by treatment with upadacitinib plus MTX combination therapy. The strength of this stu, Medicine, 101(2), e28463; 2022

BACKGROUND: The introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) into clinical practice has dramatically improve the clinical outcomes of individuals with rheumatoid arthritis (RA). However, bDMARDs are associated with high costs, which has resulted in restricted treatment access and a burden on medical insurance finances. Although biosimilars offer cost-saving, their effectiveness and safety must be established in Post-Marketing Surveillance (PMS). Infliximab (IFX), a chimeric monoclonal antibody to TNF-alpha, is the first bDMARD; its biosimilar, CT-P13, is the first biosimilar DMARD approved for RA treatment in Japan. We will evaluate whether switching from originator IFX to CT-P13 is not inferior for maintaining non-clinical relapse to continued treatment with originator IFX in RA patients achieving clinical remission. METHODS/DESIGN: This study is an interventional, multicenter, open-label, single-arm against historical control and noninferiority clinical trial with a 24-week follow-up. Eighty RA patients who are treated by originator IFX for ?24 weeks and are achieving clinical remission will be included. Patients will be switched to CT-P13 with the unchanged dosing regimen. We will evaluate disease activity by measuring clinical disease activity indices and by using musculoskeletal ultrasound (MSUS). The primary endpoint is the ratio of patients who experience a nonclinical relapse during the study period. Important secondary endpoints are the changes from the baseline of the MSUS scores. We will also comprehensively analyze the serum levels of many biomarkers such as cytokines and chemokines.DISCUSSION: The study results are expected to show the noninferiority of switching to CT-P13 over the continuation of originator IFX. The strength of this study is its prospective evaluation of therapeutic efficacy using not only clinical disease activity indices but also MSUS to accurately and objectively evaluate disease activity at the joint, Medicine, 99(30), e21151; 2020

BACKGROUND: The introduction of biological disease-modifying anti-rheumatic drugs into clinical practice has dramatically improved the clinical outcomes of individuals with rheumatoid arthritis (RA). We are conducting the IFX-SIRIUS STUDY I that evaluates whether switching from originator infliximab (IFX) to its biosimilar, CT-P13, is not inferior in maintaining nonclinical relapse to continue treatment with originator IFX in patients with RA achieving clinical remission. It is the next great issue whether disease activity can be maintained in good condition after discontinuation of CT-P13 because no evidence is available regarding the clinical value of discontinuing biosimilars in patients with RA. Thus, we will evaluate whether a condition without clinical relapse will be maintained after discontinuation of CT-P13 in patients with RA, achieving clinical remission or low disease activity during the IFX-SIRIUS STUDY I. METHODS/DESIGN: This study is an interventional, multicenter, open-label, single-arm clinical trial with a 48-week follow-up. Patients with RA who are treated with CT-P13 and sustained nonclinical relapse during the IFX-SIRIUS STUDY I will be included. Patients will discontinue CT-P13 after the study period of the IFX-SIRIUS STUDY I. We will evaluate disease activity by clinical disease activity indices and musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who do not have clinical relapse during the study period. Important secondary endpoints are the changes from the baseline of the MSUS scores. We will also comprehensively analyze the serum levels of multiple biomarkers, such as cytokines and chemokines. In addition, if a clinical relapse occurs in patients after the discontinuation of CT-P13, we will evaluate the effectiveness and safety of restarting CT-P13. DISCUSSION: The study results are expected to show the clinical benefit of the discontinuation of CT-P13 and effectiveness and safety of restarting CT-P13 af, Medicine, 99(32), e21480; 2020

Background: Familial Mediterranean fever (FMF) is an inherited disorder caused by a number of mutations of the Mediterranean fever (MEFV) gene, coding a protein named pyrin that acts as a major regulatory component of the inflammasome.The first-line drug for FMF treatment is colchicine, but 10% of patients with FMF do not respond well to colchicine.Although the efficacy of tocilizumab (TCZ), which is a recombinant, humanized, antihuman interleukin 6 (IL-6) receptor monoclonal antibody, has been reported to prevent FMF attacks, the effects of TCZ on individuals with colchicine-resistant or colchicine-intolerant FMF have not been evaluated in a randomized clinical trial. Methods/design: In this phase III, investigator-initiated, multicenter, double-blind, randomized, parallel-group trial, the efficacy and safety of TCZ will be compared with placebo in patients with colchicine-resistant or colchicine-intolerant FMF. The study will be conducted in nine centers in Japan. Participants (n = 24) will be randomly assigned to receive 162 mg of TCZ (n = 12) or placebo (n = 12) administered subcutaneously once weekly for 24 weeks. Rescue treatment will be allowed if rescue criteria are met. A primary endpoint is the number of fever attacks until 24 weeks.Secondary endpoints include the number of occurrences of accompanying symptoms during attacks; the time until a fever attack occurs; the duration of fever attacks; serum C-reactive protein and serum amyloid A;36-item Short Form Health Survey; general evaluation by a physician (100-mm visual analogue scale); body temperature; the percentage of subjects who achieve FMF 50 at 12 weeks and 24 weeks; and pharmacodynamic assessment, including the measurement of serum TCZ level and soluble IL-6 receptor. Discussion: The study is expected to produce evidence regarding the efficacy of a potential new therapeutic agent, TCZ, in improving the clinical course and outcome for patients with colchicine-resistant or colchicine-intolerant FMF., Trials, 19(1), art.no.715; 2019