Adverse drug events associated with sulfasalazine (SSZ) are likely to be responsible for lower persistence and adherence rates in patients with rheumatoid arthritis (RA) initiating triple therapy compared with combination therapy, according to the results of an observational cohort study published in Arthritis Care & Research.1

Methotrexate (MTX) alone is often used as first-line therapy in the treatment of RA2,3; however, as the disease progresses, the addition of a tumor necrosis factor inhibitor (TNFi) or the addition of SSZ and hydroxychloroquine to MTX (triple therapy) may be needed.3-5 However, there is debate about which therapy should be added to MTX.6 Therefore, researchers compared persistence and adherence rates between these 2 combination therapies in United States veterans and reported the reasons for discontinuation of combination treatment in these groups.1

They found that 12 months after combination therapy, full persistence was 45% in patients who received MTX with TNFi (n=2125) and 18% in patients in the triple-therapy group (n=171; P <.001). Likewise, adherence rates were higher in the MTX with TNFi group compared with the triple-therapy group (26% vs 11%, respectively; P <.0001). Patients in the triple-therapy group had significantly more treatment discontinuations, which was often due to adverse drug events related to SSZ. In addition, a significant number of patients who discontinued their combination therapy for RA were lost to follow-up.

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The authors concluded that, “Differences in persistence and adherence between the [MTX with TNFi] and triple therapy groups appear to be primarily related to [adverse drug events] that were most often attributed to SSZ.”1 The authors added that more research is needed to determine how to improve medication persistence and adherence and how to decrease loss to follow-up.

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References

  1. Erhardt DP, Cannon GW, Teng CC, Mikuls TR, Curtis JR, Sauer BC. Low persistence rates in rheumatoid arthritis patients treated with triple therapy are attributed to adverse drug events associated with sulfasalazine [published online September 17, 2018].Arthritis Care Res (Hoboken). doi:10.1002/acr.23759
  2. O’Dell JR. Methotrexate use in rheumatoid arthritis.Rheum Dis Clin North Am. 1997;23(4):779-796.
  3. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68(1):1-26.
  4. Lee YH, Woo JH, Rho YH, Choi SJ, Ji JD, Song GG. Meta-analysis of the combination of TNF inhibitors plus MTX compared to MTX monotherapy, and the adjusted indirect comparison of TNF inhibitors in patients suffering from active rheumatoid arthritis.Rheumatol Int. 2008;28(6):553-559.
  5. O’Dell JR. Triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine in patients with rheumatoid arthritis. Rheum Dis Clin North Am. 1998;24(3):465-477.
  6. Curtis JR, Chen L, Harrold LR, Narongroeknawin P, Reed G, Solomon DH. Physician preference motivates the use of anti-tumor necrosis factor therapy independent of clinical disease activity. Arthritis Care Res (Hoboken). 2010;62(1):101-107.