THU0094 SERONEGATIVE RHEUMATOID ARTHRITIS: MILD NO MORE
Authors: Sofia Pazmino, Annelies Boonen, Veerle Stouten, Diederik De Cock, Delphine Bertrand, Kristien Van der Elst, Johan Joly, Rene Westhovens, Patrick Verschueren
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Seronegative rheumatoid arthritis (RA) patients have been historically considered to have a milder disease. This confers a potential risk for under treatment. The quality of their response to early intensive therapies has not been thoroughly studied. <h3>Objectives</h3> To compare the disease course in seronegative and seropositive patients from the Care in early RA (CareRA) trial treated with COBRA Slim. <h3>Methods</h3> The CareRA trial included 379 patients with early RA (≤1 year) fulfilling 1987 or 2010 ACR criteria and naïve to disease modifying anti-rheumatic drugs (DMARDs). Patients were randomized to one of four different intensive treatment strategies based on methotrexate (MTX) monotherapy or synthetic (cs)DMARD combinations with or without glucocorticoid (GC) bridging. Before randomization, stratification into a high- or low-risk group according to classical poor prognostic markers (presence of erosions, positivity to rheumatoid factor (RF) and/or anti-citrullinated protein antibody (ACPA), and elevated disease activity) was conducted. One of these strategies, COBRA Slim, a combination of MTX and a prednisone remission induction scheme stepping-down from 30 mg QD, was initiated in 141 patients from both risk strata, of which 38 were negative for both RF and ACPA (seronegative). Following the treat-to-target principle, using the disease activity score in 28 joints with C-reactive protein (DAS28CRP), treatment adaptations were steered at low disease activity (≤3.2), while aiming for remission (&lt;2.6) as final outcome. The "as observed" population was analysed for differences in disease activity and radiographic progression between seronegative and seropositive patients at several time points during the 2-year study using independent sample t-test, Man Whitney-U or adjusted X<sup>2</sup> (Yate's correction for small samples). Survival analysis using Kaplan Meier was employed for time to first response to treatment. First response to treatment was defined as achieving first remission (DAS28CRP&lt;2.6) or first relevant improvement (ΔDAS28CRP&gt;1.2) after screening. Sensitivity analyses were applied on the complete CareRA cohort. <h3>Results</h3> Seronegative patients starting COBRA Slim (n=38), had similar age (53 vs 51 years, p=0.52), body mass index (25.5 vs 26.7, p=0.08), symptom duration (7.9 vs 7.2 months, p=0.23), presence of erosions (24% vs 23%, p=0.99) and gender distribution (82% vs 63%, p=0.06), compared to seropositive patients (n=103). However, parameters of disease activity were higher in seronegative patients at screening: DAS28CRP (5.1 vs 4.5, p=0.01), 28 swollen joint count (8.2 vs 5.7, p=0.02) and 28 tender joint count (10.3 vs 6.9, p=0.006). These results were corroborated when analysing the entire CareRA cohort. The mean disease activity was significantly higher in seronegative patients at the first stages (week 8 and 16), but became comparable by year 1 and 2 (Table 1). There was a significant difference in time to first treatment response between seronegative and seropositive patients, despite being treated with the same strategy, as depicted in the inverted Kaplan Meier plot (Figure 1). <h3>Conclusion</h3> In conclusion, CareRA participants with seronegative RA had a higher initial disease activity, longer time to experience a first treatment response, but achieve comparable remission status as seropositive patients with COBRA Slim, a combination of MTX with moderate dose GC bridging. This provides further evidence that, seronegative RA can no longer be considered a milder form of disease and requires an equally intensive initial treat-to-target therapy as seropositive RA. <h3>Disclosure of Interests</h3> Sofia Pazmino: None declared, Annelies Boonen: None declared, Veerle Stouten: None declared, Diederik De Cock: None declared, Delphine Bertrand: None declared, Kristien Van der Elst: None declared, Johan Joly: None declared, Rene Westhovens Grant/research support from: Bristol-Myers Squibb, Consultant for: Celltrion, Galapagos-Gilead, Patrick Verschueren Grant/research support from: Unrestricted Pfizer Grant for Early RA research