Abstract

Background:Difficult-to-treat rheumatoid arthritis (D2T RA) was recently defined by a EULAR study group (1) and, as a disease category it is largely complicated and under-researched. Patient comorbidities may play a significant role in the response to therapy with biologic disease-modifying antirheumatic drugs (bDMARDs) and in the disease classification as D2T RA.Objectives:To evaluate the impact of comorbidities [studied as total Comorbidities Count (CC) and rheumatic disease comorbidity index (RDCI)] on 6-month response to therapy with the first bDMARD in real-world clinical practice and on eventual disease designation as D2T RA.Methods:Prospective study of all RA patients who start any bDMARD in a tertiary centre University Hospital after their consent. All patient comorbidities [among a list of approximately 100 pre-specified major comorbidities] are registered by treating physicians. Response to therapy was defined as achievement of low disease activity or remission (LDA/Rem) according to simplified disease activity index (SDAI) and health assessment questionnaire (HAQ) improvement of ≥ 0.25.D2T RA patient group was defined according to the EULAR definition of D2T RA and was compared to: a/ all other patients and b/ to a sub-group of patients designated as “well-controlled RA” (follow-up ≥2 years and ≥2 visits in the last year in LDA/Rem).Logistic regression models were used to adjust for the potential confounding of age, sex, disease duration, seropositivity, number of previous synthetic DMARDs, type of 1st bDMARD initiated (TNF inhibitor vs. non-TNF inhibitor), co-administered methotrexate and corticosteroids (yes/no), baseline SDAI and HAQ and year of therapy start.Results:Analysis included 501 RA patients who received a total of 1098 bDMARD treatments. At 1st bDMARD treatment start, patients (women: 81%) had a median (IQR) age: 60 (51-68) years, disease duration: 5.4 (3-11) years, SDAI: 36 (28-46), HAQ: 1.0 (0.5-1.5), CC: 3 (2-6) και RDCI: 2 (0-3).In adjusted analyses, total comorbidity count (CC) ≤1 (vs ≥ 2) was predicting LDA/Rem at 6 months of therapy [OR (95%CI) = 4.1 (1.5-11), p=0.005], while RDCI=0 (vs. ≥ 1) was predicting HAQ improvement ≥ 0.25 [OR (95% CI) = 2.6 (1.2-6.7), p=0.046].During 2614 patient-years of follow-up, the disease in 98 patients could be classified as “D2T RA”, while 127 patients had “well-controlled RA”. Baseline independent predictors for D2T RA compared to all other patients were RDCI ≥ 1 (vs. 0) [OR = 3.3 (1.7-9.4), p = 0.024], female sex [OR =3.1 (1.01-9.5)] and age [OR = 0.97 (0.94-0.99)]. Multivariable analyses for predictors of “D2T” compared to “well-controlled” RA yielded similar results.Conclusion:In RA patients starting the first bDMARD treatment, a higher number of comorbidities at baseline is an independent predictor of lower 6-month response to therapy and final disease classification as “difficult-to-treat” RA.

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