Persistent high disease activity in the anticarbamylated protein antibody positive early arthritis patients independently of treatment

Abstract

Background: There is great interest in the identification of prognostic biomarkers informing early therapeutic decisions for the improvement of rheumatoid arthritis (RA) evolution. Promising results in early arthritis (EA) patients indicate the anti-carbamylated protein antibodies (ACarPA) may serve this function. In effect, they are associated with high baseline disease activity and, in our patients, with less improvement in the first 6-months of follow-up. This association was independent of sex, age at diagnosis, time since symptoms onset, smoking and the year of onset. However, the influence of the treatment has not been explored yet.

Objectives: We aimed to explore the influence of the initial treatment on the persistent high disease activity associated with the presence of ACarPA in EA patients.

Methods: Samples were obtained at the first visit of two EA cohorts from Hospital Universitario La Paz and Hospital Universitario La Princesa, which recruit patients within one year from the clinical onset. Information on the initial treatment and the disease activity at the baseline and at 6-months of follow-up was available from 546 patients. Treatment was categorized according to the use of corticosteroids, methotrexate (MTX) and other DMARDs, and considering changes in the first 6 months. In addition, MTX dose was considered either quantitatively or as a dichotomous variable (≥ 12.5 mg and < 12.5 mg). Main effects general linear regression was used for analysis, including the treatment and the other confounders as covariates.

Results: A large fraction (83%) of the EA patients received specific treatment from the initial visit. It comprised DMARD (50.1%), corticosteroids (10.6%), or a combination of both (39.3%). The most common DMARD was MTX (82.2%), whereas less frequently used medications included sulfasalazine (5.4%), leflunomide (3.2%), hydroxychloroquine (8.1%) and other (1.0%). The 35.5% of the treated patients maintained the treatment during the 6-month follow-up. The presence of ACarPA was associated with a 0.45 higher mean baseline DAS28 and with less decrease of DAS28 (ΔDAS28) from the baseline to 6 months of follow-up (β = 0.08, p = 0.016), as already communicated. This latter association persisted without modification after accounting for the initial treatment (DMARD, corticosteroids, and changes in treatment). In addition, it was independent of the consideration of all DMARDs in a single group, or separated into two categories: MTX and the other. Similarly, the association was independent on MTX dose, defined both as a categorical or a quantitative variable.

Conclusion: The association of ACarPA with a persistently increased disease activity in EA patients is independent of the initial treatment. These results reinforce the possibility that ACarPA can be useful as prognostic biomarkers for the first 6 months of evolution and indicate the need for personalized management of the patients carrying ACarPA.