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Tocilizumab treatment with Reducing and stopping methotreXate in patients with rheumatoid arthritis in stable low disease activity-state (T-ReX study)

T-ReX study (T-ReX study)

53

------------------------------------------------------------------- Total, n = 49 ------------------------------------------------------------------- Age, years 62 (10) Female, % 84 Weight, kg 55 (11) Disease duration, years 11 (8) Steinbrocker stage, I/II/III/IV, % 14/35/25/27 Steinbrocker class, I/II/III/IV, % 33/63/4/0 RF positive, % 79 ACPA positive, % 90 Route of TCZ, iv/sc, % 65/35 MTX dose, mg/week 8.2 (2.3) Use of glucocorticoids, % 29 Glucocorticoid dose, mg/day 2.4 (1.4) Use of csDMARDs other than MTX, % 16 Previous biologic use, % 63 CDAI 2.7 (2.5) CDAI <=2.8, % 67 SDAI 2.8 (2.5) DAS28-CRP 1.5 (0.4) CRP, mg/dl 0.04 (0.06) MMP-3, ng/ml 64.0 (28.8) HAQ-DI 0.4720.613 EQ-5D 0.822 (0.170) FSSG 5.0 (5.4) FSSG >=8, % 27 ------------------------------------------------------------------- Data are shown as mean (SD) or percentage.

Of the 53 enrolled patients, 4 did not meet the inclusion criteria. Consequently, data from 49 patients who completed the therapy up to week 36 were subjected to efficacy analysis, whereas data from 53 patients were subjected to safety analysis. Enrolled, n=53 ---> Analyzed for safety | | ---- Withdrew (Did not meet inclusion criteria), n=4 | Completed through week 36, n=49 ---> Analyzed for efficacy

-------------------------------------------------------------------- n = 53 -------------------------------------------------------------------- AE (SAE) -------------------------------------------------------------------- Total patients with >=1 AE or >=1 SAE 58% (9%) Blood and lymphatic system disorders 9% (0%) Eye disorders 2% (2%) Gastrointestinal disorders 4% (2%) Infections and infestations Bronchial infection 2% (2%) Skin infection 2% (2%) Upper respiratory infection 2% (0%) Laboratory test abnormalities Increased aspartate aminotransferase 9% (0%) Increased alanine aminotransferase 11% (0%) Increased creatinine 11% (0%) Decreased platelet count 11% (0%) Decreased white blood cell count 9% (0%) Decreased lymphocyte count 17% (0%) Neoplasms 2% (2%) --------------------------------------------------------------------

Primary endpoint: - The proportions (95% CI) of patients who maintained low disease activity without a flare at week 36 was 75.5% (61.1-86.7%). The lower limit of the 95% CI at week 36 exceeded the assumed threshold response rate of 60%. Secondary endpoints: - The proportions of patients who maintained low disease activity without a flare at weeks 12, 24, and 64 were 87.8%, 81.6%, and 69.4%, respectively. - No significant changes were observed in serum MMP-3 level, HAQ-DI, and EQ-5D from week 0 to 36. - The prevalence of GERD (defined as a FSSG score >=8) was 27.1% at week 0, 18.4% at week 12, 18.8% at week 24, and 20.0% at week 36. The prevalence of GERD at week 12 was significantly lower than that at week 0 (P = 0.025). - Multivariate logistic regression analysis revealed that female (OR: 18.0, 95% CI: 2.80-115.56) and extended dosing interval of tocilizumab (OR: 0.08, 95% CI: 0.01-0.58) were independently predict maintaining low disease activity at week 64.

Discontinuation of concomitant methotrexate is clinically feasible for maintaining low disease activity, and may be beneficial from the perspective of reducing gastrointestinal symptoms in Japanese RA patients treated with tocilizumab.

July. 02, 2020

Aug. 07, 2019

https://doi.org/10.1080/14397595.2019.1641934

No

None

https://jrct.mhlw.go.jp/latest-detail/jRCTs041180071

Kojima Toshihisa

Ngoya University Hospital

65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan

toshik@med.nagoya-u.ac.jp

Asai Shuji

Ngoya University Hospital

65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan

+81-52-744-1957

asai@med.nagoya-u.ac.jp

Complete

Oct. 13, 2016

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1) Patients fulfilled the 1987 ACR classification criteria or the new ACR/EULAR diagnostic criteria for RA
2) Patients who had a serum C-reactive protein (CRP) level of >=0.6 mg/dL at the time of initiating TCZ therapy
3) Patients with sustained low disease activity (CDAI <=10) for >=12 weeks while undergoing combination therapy with TCZ plus MTX
4) Patients had to be receiving MTX orally at a stable dose of >=6 mg/week, and TCZ at a stable dosage regimen irrespective of the route of administration, for >=12 weeks prior to obtaining informed consent. Patients receiving conventional synthetic DMARDs (csDMARDs) other than MTX or glucocorticoids were eligible, but doses had to be stable for >=12 weeks prior to obtaining informed consent

1) Patients with adherence problems
2) Patients judged as inadequate at the discretion of inevstigators

Both

Rheumatoid arthritis

At week 0, the dosing frequency of MTX was decreased from weekly to biweekly without a change in dose, regardless of the initial dose. At week 12, MTX was discontinued if low disease activity was maintained. TCZ and csDMARDs other than MTX were continued at a stable dose and interval throughout the course of the study. Glucocorticoids were continued at a stable dose up to week 36, and allowed to taper after week 36. The use of oral analgesics (non-steroidal anti-inflammatory drugs, acetaminophen, pregabalin, and tramadol) was not prohibited during the study period. One or more of the following rescue treatments were performed if the CDAI score was >10 and at the discretion of the investigator and/or upon patient request: changing the dosing frequency back to weekly administration, restarting, or increasing doses of MTX; increasing doses of or adding csDMARDs other than MTX or glucocorticoids; and administering an intraarticular injection of corticosteroids, hyaluronic acid, or lidocaine.

The proportion of patients maintaining low disease activity without a flare at week 36 (24 weeks after MTX discontinuation)

1) The proportion of patients maintaining low disease activity without a flare at week 12 and 64
2) The following parameters from week 0 to 64: disease activity (CDAI, SDAI, and DAS28-CRP), serum MMP-3 level, physical function (HAQ-DI), quality of life (EQ-5D), and GI symptoms (FSSG; prevalence of GERD was defined as a FSSG score >=8).
3) Adverse events

+81-52-744-2479

Feb. 04, 2019

none