title: Drug interaction between methotrexate and salazosulfapyridine in Japanese patients with rheumatoid arthritis.
abstract: BACKGROUND
  Methotrexate (MTX) and salazosulfapyridine (SASP) are disease-modifying drugs that are commonly used in the treatment of rheumatoid arthritis (RA), and combination therapy with MTX and SASP is recommended for RA patients who show an inadequate response to monotherapy with either drug. This study was designed to examine the interaction between the two drugs from the viewpoint of serum MTX concentration in Japanese RA patients, who were receiving combination therapy with relatively low doses of MTX and SASP.
  
  
  METHODS
  This is a 24-week open-label intervention study of stable RA patients (n= 10) with low disease activity. In these patients, who had received SASP/MTX combination therapy for at least 12 weeks, SASP was discontinued, and the patients received MTX monotherapy for the next 24 weeks. The primary outcome was change of serum MTX concentration at 12 weeks after discontinuation of SASP. Two disease activity markers, simplified disease activity index (SDAI) and disease activity score-C reactive protein (DAS28-CRP), were assessed as secondary outcomes at 24 weeks after discontinuation of SASP. We also monitored levels of matrix metalloproteinase-3 (MMP-3) and inflammatory cytokines. Patients were asked to complete a questionnaire after the study.
  
  
  RESULTS
  Serum MTX concentration in RA patients who discontinued SASP increased more than 2-fold within 4 weeks, and the higher level was maintained thereafter. No significant differences were detected in SDAI, DAS28-CRP, MMP-3 or inflammatory cytokines. Most participants reported no change in physical condition after withdrawal of SASP, and most preferred MTX monotherapy for future treatment.
  
  
  CONCLUSIONS
  Withdrawal of SASP from patients receiving SASP/MTX caused a rapid, marked increase of serum MTX concentration, without any apparent change in disease parameters or side effects. Our results suggest that SASP can be discontinued without adverse effects in stable RA patients receiving combination therapy, at least among Japanese patients receiving relatively low doses of the two drugs.
  
  
  BACKGROUND
  UMIN000024507. October 21, 2016 retrospectively registered.
authors.affiliation: Department of Pharmacy, Japan Community Healthcare Organization Kanazawa Hospital, Ha-15 Oki-machi, Kanazawa, 920-8610 Japan.|Department of Medicinal Informatics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
authors.forename: Morihiro
authors.initials: M
authors.lastname: Okada
authors.affiliation: Division of Rheumatology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Suga
authors.affiliation: Department of Pharmacy, Social Welfare Organization Saiseikai Kanazawa Hospital, 13-6 Akatsuti-machi, Kanazawa, 920-0353 Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morito
authors.affiliation: Department of Pharmacy, Japan Community Healthcare Organization Kanazawa Hospital, Ha-15 Oki-machi, Kanazawa, 920-8610 Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Pharmacy, Japan Community Healthcare Organization Kanazawa Hospital, Ha-15 Oki-machi, Kanazawa, 920-8610 Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nishigami
authors.affiliation: Division of Rheumatology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kawano
authors.affiliation: Department of Medicinal Informatics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.|Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Department of Medicinal Informatics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.|Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Sai
keywords: MTX; Polypharmacy; Rheumatoid arthritis; SASP