Abstract
BackgroundBiological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular challenge to clinicians.ObjectivesThis study aims to determine the percentage of rheumatoid arthritis (RA) patients who fail to respond to subsequent bDMARDs, describe their characteristics, and identify specific baseline and early features during the first bDMARD as possible predictors of consecutive multiple bDMARD failure.MethodsThis is a longitudinal study involving RA patients from the prospective biological cohort drawn from the La Paz University Hospital RA Registry (RA-Paz), starting a bDMARD during the years 2000 to 2019. Patients who presented insufficient response (due to primary or secondary inefficacy) to at least three bDMARDs or two bDMARDs with different mechanism of action were considered multi-refractory (MR-patients). Patients who achieved low disease activity or remission (by DAS-28) with the first bDMARD and maintained this over a follow-up period of at least 5 years were considered non-refractory (NR-patients).ResultsA total of 41 out of 402 (10%) patients were MR-patients and 71 (18%) NR-patients. In the multivariate analysis, the presence of erosions, younger age, higher baseline DAS-28 and mostly achieving delta-DAS < 1.2 after 6 months of the first bDMARD (OR 11.12; 95% CI 3.34–26.82) were independently associated with being MR-patients to bDMARDs.ConclusionsIn our cohort, 10% of patients with RA were observed to have multi-refractoriness to bDMARDs. This study supports the contention that younger patients with erosive disease and especially the early absence of clinical response to the first bDMARDs are predictors of multi-refractoriness to consecutive biologics. Hence, patients with these characteristics should be monitored more closely and may benefit from personalized treatments.
Highlights
Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients
Health Assessment Questionnaire (HAQ), Creactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), tender joint count (TJC), swollen joint count (SJC), and DAS-28-ESR were assessed at baseline and 6 months after starting the first biologic disease-modifying antirheumatic drugs (bDMARDs)
In total, 595 RA patients treated with bDMARDs through the RA-Paz Registry were identified, of which 193 discontinued treatment due to: sustained remission (13.4%), loss of follow-up (9.8%), severe infections (5.1%), neoplasms (8.8%), death (3.1%), pregnancy (3.5%), adverse events including infusional reactions (12.3%), loss of therapeutic adherence, and others (29.1%) (Supplementary Figure S1)
Summary
Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular challenge to clinicians. Biologic disease-modifying antirheumatic drugs (bDMARDs) have demonstrated their effectiveness in the treatment of rheumatoid arthritis (RA), improving the clinical course of the disease and patients’ quality of life. Despite the increasing number of therapeutic tools available, the successful treatment of certain RA patients remains challenging for clinicians. This is in part due to the severity of the disease, but may be related to the tendency of rheumatologists to cycle or switch therapies in an attempt to achieve strict disease control, following the treat-totarget recommendations [3]. Approximately two thirds of patients fail to respond in the first 6 months of treatment with first tumor necrosis factor inhibitor (TFNi) [4], and at least 12% of patients starting a second bDMARD discontinue treatment due to inefficacy [5]
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