Use of Single Non-bDMARD Linked to Long-term Joint Damage in RA

Minimal treatment of rheumatoid arthritis (RA) with a single non-biologic disease-modifying antirheumatic drug (bDMARD) may result in joint structure deterioration, regardless of prior history of inadequate response to non-bDMARDs. These data were recently published in BMC Musculoskeletal Disorders.

“Driven by recent expectations that patients in clinical trials randomized to placebo should be ‘rescued’ with active therapy within 6 months of starting treatment, the relative benefit of arresting joint damage with biologic agents beyond this period is unclear,” Jeroen P. Jansen, PhD, Tufts University School of Medicine, and colleagues stated. “With longer-term evidence of the rate of joint deterioration with placebo or minimal treatment, the efficacy of biologic agents and novel treatments might be projected beyond the placebo-controlled phase observed in clinical trials.”

The researchers therefore sought to evaluate the resulting radiographic joint damage incurred over time after minimal treatment in patients exposed and never-exposed to biologic DMARDs. They also evaluated subsets of patients with different treatment responses to non-biologic DMARDs. They conducted a literature review focused on identifying evidence of joint structural deterioration in patients with RA who underwent minimal treatment. Included articles were randomized controlled trials (RCTs) or prospective and retrospective observational cohort studies, published between 1970 and 2009 in English, German, or French.

Twelve of the studies focused on patients with inadequate responses to DMARD therapy (DMARD-IR); 32 focused on non-DMARD-IR populations. In the DMARD-IR population, continuation of treatment with azathioprine ) was associated with greater joint deterioration than continuation of methotrexate (MTX).

Only 2 studies measured deterioration using the Larsen score; in these cases deterioration of 0.52 was noted at 24 weeks in MTX patients, and deterioration varied from 0.53 points with sulfasalazine to 1.06 with gold salts at 52 weeks.

Comparatively, deterioration rate in the non-DMARD-IR population was not as large. Meta-analysis showed an increase in Total Sharp Score (TSS) from 1.56 to 5.13 at 12 weeks and 104 weeks, respectively. Up to 104 weeks, the researchers found that there was at least a 94% chance that continued DMARD treatment would result in notable joint structure deterioration. 

Further analysis showed a similar deterioration rate in head-to-head RCTs focused on treatment with leflunomide and MTX.

Summary and Clinical Applicability

Minimal treatment of RA with at a single non-biologic DMARD can impart a high risk of long-term joint structure deterioration.

“This finding is of relevance when assessing the relative benefit of arresting joint damage with new biologic agents based on findings of placebo-controlled trials in which patients randomized to placebo are ‘rescued’ with active therapy within 6 months,” the authors concluded.

Limitations and Disclosures

This study was limited by the lack of clarity found in a specific subset of included studies; the researchers found that it was unclear if patients were exclusively DMARD-IR. As a result, the investigators included these studies in the non-DMARD-IR group to ensure homogeny within the DMARD-IR cohort. Dr Jansen noted that this possible misclassification may have resulted in an overestimation of the deterioration within the non-DMARD-IR group.

Jeroen P. Jansen, PhD, has disclosed the following relevant conflicts of interest: Was employed by Mapi and was a paid consultant to Pfizer, Inc. 

Maria-Cecilia Vieira, MSc, has disclosed the following releveant conflicts of interest: Was employed by Mapi and was a paid consultant to Pfizer, Inc.

Reference

Jansen JP, Vieira M-C, Bradley JD, et al. Meta-analysis of long-term joint structural deterioration in minimally treated patients with rheumatoid arthritis. BMC Musculoskelet Disord. 2016;17(1):348; doi: 10.1186/s12891-016-1195-4

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