IgA Anti-Citrullinated Protein Autoantibodies Predict Flares During DMARD Tapering in Patients With RA

Rheumatoid arthritis. General practitioner examining a patient’s hand for signs of rheumatoid arthritis. This condition is caused by the immune system attacking the body’s own tissues, causing progressive joint and cartilage destruction. As the cartilage is worn away, new bone grows as part of the repair process. This causes stiffness and deformity of the fingers. Treatment is with anti-inflammatory drugs and physiotherapy.
The role of immunoglobulin A (IgA) anti-citrullinated protein antibodies (ACPA) in patients with rheumatoid arthritis (RA) flares is examined.

In patients with rheumatoid arthritis (RA) in stable remission, immunoglobulin A (IgA) anti-citrullinated protein antibodies (ACPA) were associated with a higher risk for flare during tapering of disease-modifying antirheumatic drugs (DMARDs), according to study results published in Rheumatology.

In patients with RA, DMARD-free remission is achieved in less than 20% of patients, it was noted. The European Alliance of Association for Rheumatology (EULAR) recommends DMARD tapering to better monitor patients for relapse. IgG ACPA are a risk factor for RA flare during tapering. Whether IgA ACPA and IgA2 ACPA play a similar role is unknown.

Patients with RA who were in stable remission for at least 6 months were selected from the randomized controlled RETRO study (ClinicalTrialsRegister.eu Identifier: 2009-015740-42). The researchers randomly assigned patients to different tapering strategies (50% reduction of DMARD or 50% reduction of DMARD for 6 months then DMARD discontinuation) or continuation of treatment. Disease activity was assessed every 3 months and serum IgA and IgA2 ACPA were measured at baseline and 12 months.

Of 108 patients, 36 were in the 50% reduction group, 33 were in the 50% reduction for 6 months group, and 39 were in the treatment continuation group.  Between baseline and 12 months, IgA2 ACPA and the percentage of IgA2 in ACPA declined by a median of 17.5% in patients who remained in remission (P <.0001). This decline was independent of treatment arm (ie, whether DMARDs were tapered or continued).

The percentage of IgA2 in ACPA was associated with disease activity among patients with flares (r=0.36; P =.046). Patients who had both IgA and IgG ACPA were at highest risk for flare.

The study authors acknowledged that a limitation of the study was the small sample size.

The researchers concluded that their study shows “that IgA ACPA can contribute to flare risk when tapering DMARDS in RA patients in stable remission.”

Disclosure: A study author declared affiliation with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of author’s disclosures.


Sokolova MV, Hagen M, Bang H, Schett G, Rech J, Steffen U; RETRO study group. IgA anti-citrullinated protein antibodies (IgA ACPA) are associated with flares during DMARD tapering in rheumatoid arthritis. Rheumatology (Oxford). Published online September 11, 2021. doi:10.1093/rheumatology/keab585