A subanalysis of the Bristol-Myers Squibb–funded APPRAISE study suggests medium- or high-level ultrasonography can determine whether patients treated with the company's rheumatoid arthritis medication abatacept have an early response.
Researchers from across Europe and the United Kingdom analyzed data from biologic-naive patients treated open-label with abatacept for 24 weeks using the Global Outcome Measures in Rheumatology-European League Against Rheumatism (OMERACT-EULAR) Synovitis Score (GLOESS). It is based on a combination of power Doppler and grayscale ultrasound (PDUS), and evaluates changes in both activity and synovitis morphology. The GLOESS scores indicated medication response as early as 7 days and continued to the end of treatment. Joint effusion was the least sensitive to treatment.
The equipment is expensive, however. In response to a query from Value-Based Care in Rheumatology, lead investigator Maria-Antonietta D'Agostino, MD, PhD, Professor of Rheumatology, Université de Versailles Saint Quentin en Yvelines, Boulogne-Billancourt, France, said the price is 20,000 to 25,000 euros (US $21,800-$27,250) for the medium-level equipment, and 80,000 to 100,000 euros (US $87,200-$109,000) for the high-level machinery. The imaging can also be time-consuming: Dr D'Agostino said that at first it takes approximately an hour to image each patient's full set of 22 paired joint sets, and with more experience 15 to 20 minutes per patient is required.
The APPRAISE study was a phase 3b, open-label, multicenter, single-arm trial that was undertaken at 21 centers across Europe. All patients received intravenous abatacept at 10 mg/kg at baseline and at weeks 2, 4, 8, 12, 16, 20, and 24, plus methotrexate, and other medications as required. Eighty-nine patients completed the trial.
Improved GLOESS scores were observed from weeks 1 to 24, although there were no correlations at any time point between changes from baseline in Disease Activity Score (DAS) 28 and GLOESS, or the component scores of GLOESS and the 28 joints used for DAS28.
"Probably the 2 tools measure different aspects of the disease activity. This latest part is developed in another paper just submitted for publication," noted Dr D'Agostino.
Higher PDUS, GLOESS, or DAS scores at baseline all correlated with less-frequent low disease activity scores or low GLOESS at 24 weeks.
Overall, changes in mean DAS28 met the threshold for clinically meaningful improvement by week 8. By week 24, 11% of the patients met the stringent American College of Rheumatology/European League Against Rheumatism Boolean criteria for remission.
Dr D'Agostino and her co-investigators were able to pare down the number of joint sets needed for accurate ultrasound assessment to 9: shoulder, elbow, wrist, metacarpophalangeal (MCP) joint 1, MCP4, proximal interphalangeal joint 2, knee, metatarsophalangeal (MTP) joint 3, and MTP5. Moreover, the results were comparable to those reported from reduced joint sets by 2 other groups.
- D'Agostino M-A, Wakefield RJ, Berner-Hammer H, et al; OMERACT-EULAR-Ultrasound Task Force. Value of ultrasonography as a marker of early response to abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results from the APPRAISE study [published online November 20, 2015]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2015-207709.