Broad antibody profile associated with improved initial RA treatment response
Among patients with rheumatoid arthritis, a broad baseline autoantibody profile correlated with a better response to early treatment, according to findings published in Arthritis Research and Therapy.
“Since autoantibodies are linked to both RA pathophysiology and treatment outcomes, they offer a unique perspective to shed light on the pathophysiological mechanisms underlying RA chronicity,” Emma C. de Moel, a PhD candidate at Leiden University Medical Center, and colleagues wrote. “Given the varying composition of the RA autoantibody profile (with its diversity in autoantigen recognition and extensive isotype switching), it appears plausible that the breadth of this profile could be associated with treatment outcomes.”
According to the researchers, no previous studies have considered the effect of baseline autoantibody profiles on a patient’s response to conventional disease-modifying anti-rheumatic drugs (DMARDs) or long-term drug-free remission. To investigate this, the researchers evaluated serum samples from 399 patients with RA from the IMPROVED trial, a multicenter, randomized controlled study that enrolled patients with early untreated RA or undifferentiated arthritis. Researchers collected samples at baseline and when patients began drug tapering.
The researchers measured IgG, IgM and IgA isotypes for anti-cyclic citrullinated peptide-2 and anticarbamylated protein antibodies, as well as IgM and IgA rheumatoid factor, and reactivity against four citrullinated and two acetylated peptides. The primary outcomes were change in disease activity score from baseline to 4 months, initial drug-free remission between 1 and 2 years of follow-up and long-term drug-free remission until last follow-up.
According to de Moel and colleagues, patients who had a broad autoantibody profile at baseline demonstrated a significantly better early treatment response. Among these patients, who had 7 to 8 isotypes, the change in disease activity score from baseline to 4 months was –2.2 (P < .001), compared with –1.5 among patients with 1 to 2 (P < .001), –1.7 among those with 3 to 4 (P = .03), and –1.8 in those with 5 to 6 (P = .04). Additionally, the researchers reported they observed similar results for anti-modified protein antibodies numbers.
Patients with a broad baseline autoantibody profile achieved less initial drug-free remission, the researchers wrote. Further, there was no longer an association with the breadth of the autoantibody response and long-term sustained drug-free remission. The researchers reported similar trends when evaluating autoantibodies at drug tapering.
“This large study shows that seropositive patients with RA with a broader autoantibody profile at baseline initially respond better to treatment and have a slightly worse chance of achieving [drug-free remission] at early stages, but that the magnitude of seropositivity does not affect the ability to taper off medication and remain in remission later in disease,” de Moel and colleagues wrote.
The researchers added, “In early stages of disease, a broad autoantibody profile may reflect active humoral immunity, which could make the underlying disease processes initially more suppressible by medication. The importance of the baseline autoantibody profile for treatment outcomes diminishes over time.” – by Jason Laday
Disclosure: The researchers report funding from the ZonMw (the Netherlands Organization for Health Research and Development)-consortium Molecular Diagnostics in RA.