Date: Tuesday, November 12, 2019
Session Title: Late-Breaking Abstracts ePoster
Session Type: Late-Breaking Abstract Poster Session
Session Time: 9:00AM-11:00AM
Background/Purpose: The optimal first-line treatment of patients (pts) with early rheumatoid arthritis (RA) is yet to be established. The primary aim was to assess and compare the proportion of pts who achieved remission with active conventional therapy (ACT) and with three different biologic therapies after 24 wks. Secondary aims were to assess and compare other efficacy measures and safety.
Methods: The investigator-initiated NORD-STAR trial (NCT01491815) was conducted in Sweden, Denmark, Norway, Finland, The Netherlands and Iceland. In this multicenter, randomized, open-label, blinded-assessor, phase 4 study pts with early RA (ACR/EULAR 2010 criteria, 18+ years old, < 24 months’ symptom duration, disease activity score (C-reactive protein, CRP (DAS28)) >3.2, ≥2 (of 66) swollen and ≥2 (68) tender joints, rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA) positive or CRP >10mg/L)) were recruited and randomized 1:1:1:1 (stratified by country, gender and ACPA). All received methotrexate (25 mg/week after one month). To this was added: Arm 1 (ACT): either oral prednisolone (tapered from 20 mg/d to 5 mg/d in 9 wks); or: sulphasalazine (2 g/day), hydroxychloroquine (35mg/kg/wk) and mandatory intra-articular (IA) triamcinolone hexacetonide (TCH) in ≤4 swollen joints (≤80 mg/visit up to wk 20); Arm 2 (CZP): certolizumab (CZP) 200 mg EOW SC (400 mg at 0, 2 and 4 wks); Arm 3 (ABA): abatacept 125 mg/wk SC; Arm 4 (TCZ): tocilizumab 8 mg/kg/4wks IV or 162 mg/wk SC. IA TCH was allowed in all arms up to wk 20. Primary outcome was clinical disease activity index remission (CDAI≤2.8) at wk 24 (ITT analysis). Dichotomous outcomes were analyzed by adjusted (stratification variables, age, body mass index (BMI) and baseline DAS28) logistic regression with non-responder imputation (NRI). Non-inferiority analyses (per protocol population) had a pre-specified margin of 15%.
Results: In total, 812 pts were randomized. At baseline age was 54.3±14.7 yrs (mean±SD), 31.2% were male, DAS28 5.0±1.1, 74.9% were RF positive and 81.9% ACPA positive, BMI 26.2±5.1 kg/m2, time since diagnosis 7 (1-18) days (median, IQR). Crude CDAI remission rates (ITT) were: ACT: 42.0%, CZP: 47.8%, ABA: 52.5%, TCZ: 41.0%. Figure 1 shows the estimated remission rates with 95% CI. Table 1 shows the primary and key secondary outcomes (ITT population). With ACT as the reference, the absolute difference in adjusted remission rate (delta) was 9% (95%CI: 0.1 to 19%) for ABA, 4% (-5 to 13%) for CZP and -1% (-10 to 9%) for TCZ. Differences in remission rates with CZP and TCZ, but not with ABA, remained within the pre-defined non-inferiority margin versus ACT (per-protocol population), Figure 2. Total numbers of (serious) adverse events (SAEs/total AEs) across ACT, CZP, ABA, TCZ were 13/552, 20/530, 10/527, 10/653, respectively.
Conclusion: High remission rates were found across all four treatment arms at 24 wks. Higher CDAI remission rate was observed for ABA versus ACT (delta 9%) and for CZP (4%), but not for TCZ (-1%). With the predefined 15% margin, ACT was non-inferior to CZP and TCZ, but not to ABA. These results underscore the efficacy and safety of active conventional therapy based on MTX combined with glucocorticoids and may guide future treatment strategies for early RA.
To cite this abstract in AMA style:Lund Hetland M, Haavardsholm E, Rudin A, Nordström D, Nurmohamed M, Gudbjornsson B, Lampa J, Hørslev-Petersen K, Uhlig T, Grondal G, Østergaard M, Heiberg M, Twisk J, Lend K, Krabbe S, Lindqvist J, Ekwall A, Lederballe Grøn K, Kapetanovic M, Faustini F, Tuompo R, Lorenzen T, Cagnotto G, Baecklund E, Hendricks O, Vedder D, Sokka-isler T, Husmark T, Ljoså M, Brodin E, Ellingsen T, Söderbergh A, Rizk M, Reckner Å, Uhrenholt L, Larsson P, Just S, Stevens D, Laurberg T, Bakland G, Olsen I, van Vollenhoven R, NORD-STAR Study Group. A Multicenter Randomized Study in Early Rheumatoid Arthritis to Compare Active Conventional Therapy versus Three Biological Treatments: 24 Week Efficacy and Safety Results of the NORD-STAR Trial [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/a-multicenter-randomized-study-in-early-rheumatoid-arthritis-to-compare-active-conventional-therapy-versus-three-biological-treatments-24-week-efficacy-and-safety-results-of-the-nord-star-trial/. Accessed March 28, 2023.
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