Enhanced treatment strategies and distinct disease outcomes among autoantibody-positive and -negative rheumatoid arthritis patients over 25 years: A longitudinal cohort study in the Netherlands

Abstract

Background Based on different genetic and environmental risk factors and histology, it has been proposed that rheumatoid arthritis (RA) consists of 2 types: autoantibody-positive and autoantibody-negative RA. However, until now, this remained hypothetical. To assess this hypothesis, we studied whether the long-term outcomes differed for these 2 groups of RA patients. Methods and findings In the Leiden Early Arthritis Clinic cohort, 1,285 consecutive RA patients were included between 1993 and 2016 and followed yearly. Treatment protocols in routine care improved over time, irrespective of autoantibody status, and 5 inclusion periods were used as instrumental variables: 1993-1996, delayed mild disease-modifying antirheumatic drug (DMARD) initiation (reference period); 1997-2000, early mild DMARDs; 2001-2005, early methotrexate; 2006-2010, early methotrexate followed by treat-to-target adjustments; 2011-2016, similar to 2006-2010 plus additional efforts for very early referral. Three longterm outcomes were studied: sustained DMARD-free remission (SDFR) (persistent absence of clinical synovitis after DMARD cessation), mortality, and functional disability measured by yearly Health Assessment Questionnaire (HAQ). Treatment response in the short term (disease activity) was measured by Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR). Linear mixed models and Cox regression were used, stratified for autoantibody positivity, defined as IgG anti-CCP2 and/or IgM rheumatoid factor positivity. In total, 823 patients had autoantibody-positive RA (mean age 55 years, 67% female); 462 patients had autoantibody-negative RA (age 60 years, 64% female). Age, gender, and percentage of autoantibody-positive patients were stable throughout the inclusion periods. Disease activity significantly decreased over time within both groups. SDFR rates

Factors that influence biological survival in rheumatoid arthritis: results of a real-world academic cohort from the Netherlands

“…Previous literature already showed that the presence of autoantibodies in RA is associated with a worse treatment response and outcome. Moreover, autoantibody-negative RA patients have a better treatment response compared to autoantibody-positive RA patients when given similar therapies [ 21 ]. In accordance with previous literature, we found a shortened biological survival due to inefficacy or adverse events in RF-positive RA patients but also the inability to taper TNF inhibitors after reaching remission in ACPA-positive RA patients [ 22 ].…”

Possibilities for personalised medicine in rheumatoid arthritis: hype or hope

“…Early (rheumatoid) arthritis can be divided into the following three clinical phenotypes: undifferentiated arthritis (UA), autoantibody (ACPA and RF) negative RA (RA−) and autoantibody positive RA (RA+). 6 14 UA refers to patients with arthritis who do not meet the 2010 and 1987 classification criteria for RA, which corresponds with the patients with early arthritis described in the EULAR recommendations for early arthritis. 15 16 Patients with RA do fulfil either the 2010 or 1987 classification criteria for RA.…”

“… 16 The subdivision of these phenotypes was originally based on differences in (progression of) erosive disease, while nowadays only DMARD-free remission (DFR) rates and the number of treatment intensifications needed to reach remission differ. 6 13 14 On the other hand, all clinical phenotypes have a similar impact on patients’ lives when patient-reported outcomes are compared. 14 From a pathophysiological point of view, genetic as well as environmental risk factors differ between RA+ and RA−.…”

“… 4 5 For RA, personalised treatment based on distinct phenotypes has been proposed in the literature. 6 7 Therefore, in this viewpoint we will discuss current evidence and future possibilities for personalised medicine in RA.…”

Challenges in the diagnosis of early rheumatoid arthritis in times of COVID-19

“…8 Equally important, despite the incidence of autoantibody-negative RA is increasing, 4 restrictions imposed by the pandemic, together with the erroneous but common beliefs attributing to this disease subtype a harmless course, may leave patients with less abrupt onsets underdiagnosed, with further impact on prognosis which remains per se unfavourable even in the modern treatment era. 7 The challenge is thus to keep on fighting COVID-19 without forgetting non-COVID-19 diseases.…”