Post-marketing surveillance of high-dose methotrexate (>8 mg/week) in Japanese patients with rheumatoid arthritis: A post hoc sub-analysis of patients according to duration of prior methotrexate use

Abstract

Objectives

To explore whether the duration of prior low-dose methotrexate treatment (MTX; ≤8 mg/week) influences the safety and effectiveness of high-dose MTX (>8 mg/week) in Japanese patients with rheumatoid arthritis (RA).

Methods

This post hoc sub-analysis of a Japanese post-marketing surveillance study evaluated patients initiating high-dose MTX with ≥1 year or <1 year prior low-dose MTX use. Over 24 or 52 weeks, adverse drug reactions (ADRs) were monitored, and effectiveness was assessed using the Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4 (ESR)].

Results

One thousand two hundred and ninety-two MTX ≥1 year and 1001 MTX <1 year patients were included. The incidence of ADRs during the 24- and 52-week follow-up period was significantly more frequent in MTX <1 year than ≥1 year patients and serious ADRs were significantly higher in MTX <1 year than ≥1 year patients during the 52-week follow-up period (all p < .05). Over both follow-up periods, the mean DAS28-4 (ESR) significantly decreased from baseline for all groups. Remission and low disease activity rates (DAS28-4 (ESR) <2.6 and <3.2, respectively) increased from baseline for all groups.

Conclusion

High-dose MTX reduced disease activity regardless of prior treatment duration, but ADRs occurred more frequently among MTX <1 year patients compared to MTX ≥1 year patients.

Keywords:

• Effectiveness
• methotrexate
• post-marketing surveillance
• rheumatoid arthritis
• safety

Acknowledgements

The authors thank all the physicians and patients who participated in this PMS study. The PMS study was sponsored and implemented by Pfizer Japan Inc, on behalf of the manufacturers of MTX, which included Sawai Pharmaceutical Co Ltd, Shiono Chemical Co Ltd, Mitsubishi Tanabe Pharma Corporation, Towa Pharmaceutical Co Ltd, and Sandoz Co Ltd According to the Pharmaceutical Affairs Law of Japan and the regulations promulgated thereunder, the Sponsor (Pfizer) was required to conduct a PMS study as a condition for the marketing approval of high-dose MTX 8–16 mg/week for RA. Pfizer was responsible for the development of the study protocol (with instructions from the Pharmaceuticals and Medical Devices Agency) and for the analysis of the study data. Medical writing support, under the direction of the authors, was provided by Kirsten Woollcott, MSc, and Robert Morgan, MSc, CMC Connect, McCann Health Medical Communications, and was funded by Pfizer Japan Inc., Tokyo, Japan, in accordance with Good Publication Practice (GPP3) Guidelines [Ann Intern Med. 2015;163:461–4].

Conflict of interest

Y. Suzuki has received research funding from Chugai Pharmaceutical Co Ltd, Teijin Pharma Ltd, Asahi Kasei Pharma Co, and has received speaking fees and/or honoraria from Eisai Co Ltd, Ono Pharmaceutical Co Ltd, Mitsubishi Tanabe Pharma Co Ltd, Maruho Co Ltd, GlaxoSmithKline K.K. and Pfizer Japan Inc. T. Hirose, N. Sugiyama, K. Nomura, and E. Campos Alberto are employees and shareholders of Pfizer Japan Inc.

Data availability statement

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