OP0030 Corticosteroid bridging strategies with methotrexate monotherapy in early rheumatoid and undifferentiated arthritis; a comparison of efficacy and toxicity in the treach and improved studies

Abstract

BackgroundWhat is the optimal glucocorticoid (GC) bridging therapy with MTX monotherapy in early arthritis?ObjectivesTo compare short term clinical efficacy of high and low dose GC tapering schedules with MTX monotherapy in 2 clinical trials in early rheumatoid arthritis (RA) and undifferentiated arthritis (UA) patients.MethodsIn tREACH, early RA and UA (arthritis in ≥1 joint(s),<1 year symptoms) patients were randomised to 3 different treatment arms. For this analysis we only use the data of arm C: oral GCs (prednisone) (15 mg/day, tapered to 0 in 10 weeks) with MTX monotherapy (25 mg/week); low dose GC tapering schedule (LDGC).In IMPROVED RA and UA (arthritis in ≥1 joint and ≥1 other painful joint,<2 years symptoms) patients were treated with prednisone (60 mg/day, tapered in 7 weeks to 7.5 mg/day, continued to 4 months)+MTX monotherapy (25 mg/week); high dose GC tapering schedule (HDGC). We compared%DAS-remission (<1.6) and low disease activity (≤2.4) at first evaluation (3 months tREACH, 4 months IMPROVED) and DAS and HAQ over time. After multivariate normal imputation we applied generalised estimating equations (GEE) for linear outcomes and logistic regression models for binary outcomes, adjusted for potential baseline confounders (figure 1). Adverse events were compared between treatment arms using χ2-square tests.ResultsPatients with a HDGC (n=610) had shorter symptom duration and higher HAQ, were less often seropositive (ACPA positive 56.0% vs 77.3%, RF positive 58.1% vs 65%) and more often had UA (20.3% vs 2.1%) than patients with a LDGC (n=97). Baseline DAS was comparable.At the first evaluation time point (median 3.06 (IQR 2.99–3.22) months in LDGC, 4.01. (3.8–4.17) in HDGC) DAS and HAQ had decreased significantly less after 3 months LDGC: DAS β (95% CI) 0.500 (0.276; 0.725), and HAQ 0.330 (0.189; 0.470) than after 4 months HDGC (figure 1).Compared to the HDGC patients, patients with the LDGC had a significantly lower chance of achieving DAS-remission 63.4% vs 28.9% (OR (95% CI) 0.215 (0.124; 0.373) and low disease activity 80.6% vs 55.7% ((OR (95% CI) 0.249 (0.143; 0.435)). Presence of ACPA was positively associated with achieving DAS-remission in the HDGC group, but not in the LDGC group. Per 100 patient years, 7.98 serious adverse events were reported in the HDGC and 23.4 in the LDGC (p=0.004). Hypertension, hyperglycemia (>7.8 mmol/L), gastrointestinal complaints and liverenzymes above normal were reported in similar frequencies across all groups. In patients with a LDGC more headaches, skin rashes, creatinine above normal range and any decrease in haematology blood counts were reported (data not shown).Abstract OP0030 – Figure 1 A:Predicted DAS over time, B: PRedicted HAQ over time. All predictions are from multiple imputed models, adjusted for age, gender body mass index, presence of ACPA, presence of rheumatoid factor, symptom duration, effect over time (in GEE) and baseline DAS (for binary out-comes). DAS, Disease Activity Score; HAQ Health Assessment Questionnarie; HD GC, high dose glucocortico...