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Overall multibiomarker disease activity scores are insufficient for determining rheumatoid arthritis disease activity following repository corticotropin injection, according to data published in Arthritis Care & Research.
“Disease control was more accurately assessed with using the Clinical Disease Activity Index (CDAI) or the Disease Activity Score 28–erythrocyte sedimentation rate (DAS28‐ESR),” Roy Fleischmann, MD, MACR, co-medical director of the Metroplex Clinical Research Center, and clinical professor of medicine at the University of Texas Southwestern Medical Center, in Dallas, told Healio Rheumatology. “Patients may be in low disease activity or remission by these validated metrics, and this may not be apparent if one uses the multibiomarker disease activity scores (MBDA).”
To compare the MBDA score’s ability to assess RA disease activity after repository corticotropin injection (RCI; Acthar Gel, Mallinckrodt Pharmaceuticals) to that of the DAS28-ESR and the CDAI, Fleischmann and colleagues conducted a multicenter, randomized, placebo‐controlled trial. Participants were adults with persistent, active RA with a DAS28-ESR of more than 3.2 despite disease-modifying antirheumatic drug and glucocorticoid use. In addition, all participants were required to be receiving glucocorticoids for at least 12 weeks and a stable dose of prednisone or equivalent for 4 weeks prior to screening.
Patients must have also received methotrexate and one biologic, targeted synthetic or conventional synthetic DMARD, or treatment with one biologic DMARD for at least 12 weeks before screening.
During the study’s open-label period, 259 participants received 80 U of RCI twice weekly for 12 weeks. Those who achieved low disease activity — defined as a DAS28-ESR of less than 3.2 — at week 12 then moved on to the double-blind period, where they were randomized to receive either 80 U of RCI or placebo twice weekly for another 12 weeks. In all, 154 participants were randomized 1:1 to the two groups, with the aim of assessing low disease activity maintenance. Low disease activity was assessed at baseline, week 12 and week 24 using the DAS28-ESR, CDAI and MBDA.
The researchers then analyzed the changes in disease activity, as well as the correlations between MBDA scores and both DAS28‐ESR and CDAI scores.
According to the researchers, changes in DAS28‐ESR and CDAI scores from baseline suggested that RCI therapy led to clinically meaningful improvements in disease activity. However, improvements in MBDA scores from baseline were below the minimally important difference threshold. For the DAS28‐ESR and CDAI scores, correlations with total MBDA and individual component scores were generally low (r 0.3), and occasionally moderate (r between 0.3 and 0.5).
“Importantly, although the MBDA did correlate with the DAS28-ESR and CDAI, the correlation was very low indicating that they do not correlate well,” Fleischmann said. “In addition, although there was a statistically significant change in the MBDA, the mean change was less than the minimally clinically important difference strongly suggesting that the statistical significance is not reflective of the clinical significance.”
According to Fleischmann, these results are similar to what has been previously reported with other molecules, including abatacept (Orencia, Bristol Myers Squibb), adalimumab (Humira, AbbVie), baricitinib (Olumiant, Eli Lilly & Co.) and tocilizumab (Actemra, Genentech) in prospective studies.
“The MBDA does not correlate well with the validated disease metrics suggested for clinical use by the American College of Rheumatology,” he said. “One might assume these results would be similar with other molecules with a similar mechanism of action, such as other TNF inhibitors, IL-6 inhibitors and JAK inhibitors, but one cannot know for sure unless these specific molecules were studied in a similar manner.”
“Until then, I would be cautious about relying on the MBDA to assess clinical disease control with these other molecules,” Fleischmann added. “The treat-to-target approach for the treatment of RA is well established. The treatment target should include a metric which examines joints and not the MBDA. Hopefully, a biomarker — or biomarkers — will be developed that can accurately reflect disease activity with high correlation with our validated metrics.”