Interventions to Delay RA Onset

Abatacept was also associated with improvements in pain scores, functional well-being and quality of life-measurements during treatment, as well as lower scores of subclinical synovitis determined by ultrasound. These effects were not sustained beyond the treatment period, but this might be partly because APIPPRA did not remove patients from the study who had developed RA, unlike, for example, TREAT EARLIER and ARRIA, which showed sustained improvements in patient-reported outcomes after treatment cessation.^1,2,12

Dr. Cope

APIPPRA lead investigator, Andrew P. Cope, BSc, MBBS, PhD, FRCP, HFEA, Versus Arthritis professor of rheumatology and head of the Centre for Rheumatic Diseases at King’s College London, points out that the modest differences in participant-reported outcomes may partly be due to challenges of evaluation in patients with lower symptom burden; measures such as the Disease Activity Score-28 have not been validated in this population and may not be appropriate in it.

Overall, the results from APIPPRA complement those of the ARIAA study, which looked at abatacept given for six months to patients with joint pain, positive ACPA and subclinical joint inflammation at baseline. ARIAA demonstrated improvements in synovitis, tenosynovitis and/or osteitis via MRI in 57% of patients in the abatacept group vs. 31% of patients in the placebo group, and these effects were maintained one year after stopping treatment.²

“Some of the earlier prevention trials had promising signals related to either quality of life measures or improved biomarkers,” says Dr. Sparks, “but having these two trials that truly show that we could delay onset—I think is a real proof of principle that this is possible.”

Dr. Cope and colleagues are soon to complete long-term follow up of the APIPPRA trial cohort for an additional four to eight years (based on time of accrual), which should yield more information about long-term potential impacts on prevention vs. delay of RA onset.

Critiques & Considerations

Dr. Sparks points out that some in the field are still skeptical about these sorts of preventive investigations in patients at high risk of RA. “Did these patients just have RA the whole time? That’s the critique given.”

Questions about whether patients “really have” RA can trend toward the philosophical. On one hand, although the classification criteria are particularly helpful for research studies, RA is ultimately a clinical diagnosis. Dr. Sparks points out that variations exist in the way rheumatologists assess synovitis by exam, particularly for borderline cases. Some rheumatologists may also assess synovitis by ultrasound or by MRI, but not all do, which can influence interpretation and add to variation in assessment.