CHICAGO – The commercially available multibiomarker disease activity score assay and power Doppler ultrasound at baseline in rheumatoid arthritis patients treated with tofacitinib predicted 12-week responses on some clinical, imaging, and biomarker endpoints, according to findings from an investigator-initiated, open-label study.
Dr. Elena Hitraya
The blood test–based multibiomarker disease activity (MBDA) score, which is calculated using measurements of 12 inflammatory biomarkers to score RA disease activity on a 0-100 point scale (Vectra DA, Myriad Autoimmune), also appears to track RA patients’ responses to rituximab, according to a post-hoc analysis of three cohort studies.
The findings of both studies were presented in posters at the annual meeting of the American College of Rheumatology. They are the first studies to evaluate early musculoskeletal ultrasound (MSUS) and MBDA score changes as predictors of response to tofacitinib in patients with RA, and the first to assess the ability of the MBDA score to track response to rituximab treatment. They provide valuable information that can help guide patient treatment and thereby improve outcomes, Elena Hitraya, MD, PhD, chief medical officer for Crescendo Bioscience/Myriad Autoimmune, San Francisco, said in an interview.
In the tofacitinib study, 25 RA patients with a mean age of 52 years, mean disease duration of 10.4 years, baseline Disease Activity Score 28-joint count (DAS28) greater than 3.2, and power Doppler ultrasound (PDUS) scores greater than 10 were treated with the approved oral tofacitinib dose of 5 mg twice daily. Assessments at baseline, 2 weeks, and 12 weeks included MSUS to score 34 joints for PDUS and gray scale ultrasound (GSUS), MBDA score, clinical disease activity index (CDAI), and DAS28, according to Amir Razmjou, MD, of the University of California, Los Angeles, and his colleagues.
Statistically significant improvement was seen on all measures over the 12-week study period (all at P less than .0001). For example, from baseline to 12 weeks the PDUS score improved from 28.6 to 12.2, GSUS score improved from 48.4 to 37.9, MBDA score improved from 50.6 to 39.6, CDAI score improved from 39.9 to 21.6, and DAS28–erythrocyte sedimentation rate (DAS28-ESR) score improved from 6.3 to 4.6, they said, noting further that baseline PDUS and MBDA scores significantly predicted CDAI and DAS28 responses at 12 weeks (P less than .01).
In the rituximab study, the MBDA score tracked disease activity in 57 RA patients from three different cohorts with a mean age of 57 years and mean disease duration of 11.5 years. Changes in the MBDA score reflected the degree of treatment response, Nadia M.T. Roodenrijs of University Medical Center Utrecht (the Netherlands) and her colleagues reported.
All patients were treated with 1,000 mg rituximab and 100 mg methylprednisolone on days 1 and 15, and MBDA score was assessed at baseline and 6 months.
MBDA scores correlated significantly with change from baseline to 6 months in DAS28-ESR (r = 0.60), DAS28–high-sensitivity C-reactive protein, (DAS28-hsCRP; r = 0.48), ESR (r = 0.48), and hsCRP (r = 0.71), and with European League Against Rheumatism (EULAR) good or moderate response at 6 months based on DAS28-ESR (adjusted odds ratio, 0.91).
Extensive work has been done to validate the MBDA score for assessing disease activity, and it has been shown to perform well for predicting response to a variety of disease-modifying antirheumatic drugs and biologic agents, Dr. Hitraya explained.
Additionally, multiple studies have demonstrated that the MBDA score defines risk categories for radiographic progression and performs better than traditional measures of disease activity for identifying those at increased risk of radiographic progression, which can help physicians mitigate associated risks through increased surveillance and therapeutic choices, she said.
“Having data for these specific molecules [tofacitinib and rituximab] is very important for rheumatologists,” Dr. Hitraya said.
The tofacitinib study was supported by Pfizer. Dr. Razmjou and Dr. Roodenrijs each reported having no disclosures.
SOURCE: Razmjou A et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 582; Roodenrijs N et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 1500.