ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 0825

An Investigator-initiated Multicenter Randomized Study in Early Rheumatoid Arthritis of Active Conventional Therapy versus Three Biological Treatments: 48 Week Clinical and Radiographic Results of the NORD-STAR Trial

Mikkel Ostergaard1, Ronald van Vollenhoven2, Anna Rudin3, Merete Hetland4, Marte S Heiberg5, Dan Nordström6, Michael Nurmohamed7, Bjorn Gudbjornsson8, Lykke Ørnbjerg9, Pernille Bøyesen10, Inge Olsen11, Kristina Lend12, Kim Hørslev-Petersen13, Till Uhlig14, Tuulikki Sokka-Isler15, Gerdur Grondal8, Simon Krabbe16, Joakim Lindqvist17, Inger Gjertsson18, Daniel Glinatsi9, Meliha Kapetanovic19, Anna-Birgitte Aga10, Francesca Faustini20, Pinja Parmanne21, Tove Lorenzen22, Cagnotto Giovanni23, Johan Back24, Oliver Hendricks25, Daisy Vedder26, Tuomas Rannio27, Emma Grenholm28, Maud Kristine Ljoså29, Eli Brodin30, Hanne Merete Lindegaard31, Annika Söderbergh32, Milad Rizk33, Elsa Hermansson34, Per Larsson35, Line Uhrenholt36, Søren Andreas Just37, David John Stevens38, Trine Bay Laurberg39, Gunnstein Bakland40, Espen Haavardsholm41 and Jon Lampa17, 1Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, and Department of Clinical Medicine, University of Copenhagen, Glostrup, Denmark, 2Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam Rheumatology Center, Amsterdam, Netherlands, 3Rheumatology Clinic, Sahlgrenska University Hospital, Sahlgrenska Academy of University of Gothenburg, Gothenburg, Sweden, 4DANBIO and COPECARE, Centre for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark, 5Diakonhjemmet Hospital, Oslo, Norway, 6Division of Internal Medicine and Rheumatology, Helsinki University Hospital, Helsinki, Finland, 7Reade and Amsterdam University Medical Center, location VUmc, Amsterdam, Netherlands, 8Landspitali University Hospital, University of Iceland, Reykjavik, Iceland, 9Copenhagen Center for Arthritis Research, COPECARE, Glostrup, Denmark, 10Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, 11Oslo University Hospital, Oslo, Norway, 12Department of Medicine, Rheumatology Unit, The Karolinska Institute, Stockholm, Sweden, 13King Christian X's Hospital for Rheumatic Diseases, Gråsten, Denmark, 14Diakonhjemmet Hospital, University of Oslo, Oslo, Norway, 15University of Eastern Finland, Jyväskylä Central Hospital, Jyväskylä, Finland, 16Radiologisk Afdeling, Herlev Universitetshospital, Herlev, Denmark, 17Karolinska University Hospital, Stockholm, Sweden, 18Dept. of Rheumatology, Sahlgrenska University Hospital, Gothenborg, Sweden, 19Dept. of Clinical Sciences, Skåne University Hospital, Lund, Sweden, 20Dept. of Medicine, Rheumatology, Karolinska University Hospital, Stockholm, Sweden, 21Division of Rheumatology, Helsinki University Hospital, Helsinki, Finland, 22Dept. of Rheumatology, Silkeborg University Hospital, Silkeborg, Denmark, 23Dept. of Clinical Sciences, Skåne University Hospital, Malmö, Sweden, 24Dept. of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden, 25Danish Hospital for Rheumatic Diseases, Sønderborg, Denmark, 26Dept. of Rheumatology, Reade, Amsterdam, Netherlands, 27Finland Central Hospital, Jyväskylä, Finland, 28Dept. of Rheumatology, Falunl, Falun, Sweden, 29Dept. of Rheumatology, Ålesund Hospital, Ålesund, Norway, 30Dept. of Rheumatology, Haukeland University Hospital, Haukeland, Norway, 31Rheumatology Research Unit, Odense University Hospital, Odense, Denmark, 32Dept. of Rheumatology, Örebro University Hospital, Örebro, Sweden, 33Rheumatology Clinic, Västmanlands Hospital Västerås, Västerås, Sweden, 34Dept. of Rheumatology, Linköping University Hospital, Linköping, Sweden, 35Academic Specialist Center, Stockholm, Sweden, 36Department of Rheumatology, Aalborg University Hospital, Aalborg, Denmark, 37Section of Rheumatology, Dept. of Medicine, Svendborg Hospital, Svendborg, Denmark, 38Dept. of Rheumatology, University Hospital of Trondheim, Trondheim, Norway, 39Dept. of Rheumatology, Aarhus University Hospital, Aarhus, Denmark, 40Dept. of Rheumatology, University Hospital of North Norway, Tromsø, Norway, 41[email protected], Oslo, Norway

Meeting: ACR Convergence 2021

Keywords: , , , ,

Session Information

Date: Sunday, November 7, 2021

Title: RA – Treatments Poster I: Comparative Effectiveness, Biosimilars, Withdrawal, & the Real World (0813–0845)

Session Type: Poster Session B

Session Time: 8:30AM-10:30AM

Background/Purpose: The optimal first-line treatment of patients (pts) with early rheumatoid arthritis (eRA) is yet to be established. The main objectives were to assess and compare clinical and radiographic outcomes after 48 weeks of active conventional therapy (ACT) with conventional synthetic (cs)DMARDs plus glucocorticoid versus each of three biological (b)DMARDs with different modes of action (certolizumab pegol, abatacept and tocilicumab), all combined with methotrexate (MTX).

Methods: The NORD-STAR trial (NCT01491815) was conducted in the Nordic countries and Netherlands (1). In this investigator-initiated, randomized, open-label, blinded-assessor study pts with treatment-naïve, eRA with DAS28 >3.2, and positive RF or ACPA, or CRP >10mg/L were randomized 1:1:1:1. Methotrexate (25 mg/week) was combined with: 1) ACT: oral prednisolone (tapered quickly; discontinued at wk 36); or: sulphasalazine, hydroxy­chloroquine and mandatory intra-articular (IA) glucocorticoid (GC) injections in swollen joints; 2) certolizumab 200 mg EOW SC (CZP); 3) abatacept 125 mg/wk SC (ABA); tocilizumab 162 mg/wk SC (TCZ). IA GC was allowed in all arms except wks 20-24 and 44-48. Co-primary outcomes were clinical disease activity index remission (CDAI≤2.8) at wk 48 and change in total van der Heijde-modified Sharp Score from baseline to wk 48 (∆vdHSSw0-w48).

As predefined in the statistical analysis plan, 6 primary null hypotheses were tested: no difference between ACT and each of the 3 bDMARDs for each of the two co-primary outcomes. Multiplicity was handled by Bonferroni correction of the co-primary outcomes (resulting in a 0.025 significance level per outcome), and then applying Dunnet’s multiple comparison procedure with ACT as reference within each outcome. Logistic regression with non-responder imputation (NRI) (dichotomous outcomes) and analysis of covariance (ANCOVA) (∆vdHSS) were applied with inter- or extrapolation for missing values and adjusted for baseline value (only ANCOVA), gender, ACPA status and country.

Results: 812 pts were randomized. Table 1 shows baseline data.

Adjusted CDAI remission rates at w48 were: 59.3% (for ABA), 52.3% (CZP), 51.9% (TCZ) and 39.2% (ACT), with the null hypothesis formally rejected for ACT vs ABA (adjusted difference +20.1%; adjusted p< 0.001) and ACT vs CZP (+13.1; p=0.021), but not for ACT vs TCZ (+12.7; p=0.030). For key secondary clinical outcomes improved clinical outcomes in bDMARD groups compared to ACT were consistently found (Table 2).

Adjusted estimated mean ∆vdHSSw0-w48 was 0.62 (ABA), 0.47 (CZP), 0.50 (TCZ) and 0.45 (ACT), i.e consistently low. None of the radiographic null hypotheses were rejected (Table 2).

Safety profiles were as previously reported. The total number of serious adverse events (% patients with ≥1 event) were: ABA 21 (8.3%), CZP 28 (12.4%), TCZ 20 (9.2%) and ACT 23 (10.7%).

Conclusion: Compared with ACT (csDMARD+glucocorticoids), statistically significant superiority regarding CDAI remission rates was demonstrated for ABA+MTX and CZP+MTX, and not for TCZ+MTX. Radiographic progression was low, without significant differences between treatments.

References: 1. Hetland et al. BMJ 2020; 371:m4328

Table 1: Demographics and patient characteristics at baseline (ITT population).

Table 2: Primary and key secondary outcomes at week 48 (ITT population).

Figure 1: Adjusted CDAI remission rates at week 48 (left) and adjusted change in van der Heijde modified total Sharp score from baseline to week 48 (right)

Disclosures: M. Ostergaard, AbbVie, 2, 5, 6, Bristol-Myers Squibb, 2, 6, Celgene, 2, 6, Novartis, 2, 5, 6, Boehringer Ingelheim, 2, 6, Eli Lilly, 2, 6, Hospira, 2, 6, Janssen, 2, 6, Merck, 2, 5, 6, Novo, 2, 6, Orion, 2, 6, Pfizer Inc, 2, 6, Regeneron, 2, 6, Roche, 2, 6, UCB, 2, 6, GSK, 2, 6, Mundipharma, 2, 6, Schering-Plough, 2, 6, Takeda, 2, 6, Wyeth, 2, 6, Centocor, 2, 5, 6; R. van Vollenhoven, Bristol Myers Squibb, 2, 5, Eli Lilly, 5, UCB, 2, 5, 6, Pfizer, 2, 6, 12, Support for educational programs; institutional grants, Roche, 12, Support for educational programs; institutional grants, Janssen, 2, 6, AbbVie, 2, 6, AstraZeneca, 2, Biotest, 2, GlaxoSmithKline, 2, 6, Biogen, 2, Galapagos, 2, 6, Gilead, 2, Sanofi, 2, Servier, 2, Vielabio, 2; A. Rudin, AstraZeneca, 12, financial support; M. Hetland, Biogen, 2, 5, 6, Celltrion, 2, 6, Janssen Biologics B.V, 2, 6, MSD, 2, 6, Pfizer, 2, 5, 6, Samsung Bioepis, 2, 6, AbbVie, 5, BMS, 5, Eli Lilly Denmark A/S, 5, 12, personal fees, Lundbeck Fond, 5, Roche, 5, Sandoz, 5, Novartis, 5, Merck, 5, Orion Pharma, 12, personal fees, Medac, 6; M. Heiberg, Roche, 6; D. Nordström, Abbvie, 6, BMS, 6, Lilly, 6, MSD, 6, Novartis, 6, Pfizer, 6, Roche, 6, UCB, 6, Celgene, 5; M. Nurmohamed, Pfizer, 2, 5, 6, AbbVie, 2, 5, 6, Roche, 2, 5, 6, Bristol-Myers Squibb, 2, 5, 6, MSD, 2, 5, 6, Mundipharma, 2, 5, 6, UCB, 2, 5, 6, Janssen, 2, 5, 6, Menarini, 2, 5, 6, Lilly, 2, 5, 6, Celgene, 2, 5, 6, Sanofi, 2, 5, 6, Gilead/Galapagos, 2, 5; B. Gudbjornsson, Novartis Healthcare, 2, Amgen, 6; L. Ørnbjerg, Novartis Healthcare, 5; P. Bøyesen, None; I. Olsen, None; K. Lend, None; K. Hørslev-Petersen, None; T. Uhlig, None; T. Sokka-Isler, AbbVie, 2, Amgen, 2, BMS, 2, Celgene, 2, DiaGraphIT, 2, Medac, 2, MSD, 2, Novartis Healthcare, 2, Orionpharma, 2, Pfizer, 2, Roche, 2, Sandoz, 2, UCB, 2; G. Grondal, None; S. Krabbe, Novartis Healthcare, 5, AbbVie, 5, MSD, 5; J. Lindqvist, None; I. Gjertsson, None; D. Glinatsi, AbbVie, 2; M. Kapetanovic, None; A. Aga, AbbVie, 2, Eli Lilly, 2, Novartis Healthcare, 6, Pfizer, 6; F. Faustini, None; P. Parmanne, Pfizer, 12, Attending virtual congress; T. Lorenzen, None; C. Giovanni, None; J. Back, None; O. Hendricks, Pfizer, 6, AbbVie, 6, Novartis Healthcare, 6; D. Vedder, None; T. Rannio, None; E. Grenholm, None; M. Ljoså, None; E. Brodin, None; H. Lindegaard, None; A. Söderbergh, Roche, 6; M. Rizk, None; E. Hermansson, None; P. Larsson, None; L. Uhrenholt, None; S. Just, None; D. Stevens, None; T. Bay Laurberg, UCB, 2; G. Bakland, UCB, 2; E. Haavardsholm, NORDFORSK, 5, Norwegian Regional Health Authorities, 5, South-Eastern Norwegian Regional Health Authority, 5, Pfizer, 6, AbbVie, 6, Celgene, 6, Novartis Healthcare, 6, Janssen, 6, Gilead, 6, Eli-Lilly, 6, UCB, 6; J. Lampa, None.

To cite this abstract in AMA style:

Ostergaard M, van Vollenhoven R, Rudin A, Hetland M, Heiberg M, Nordström D, Nurmohamed M, Gudbjornsson B, Ørnbjerg L, Bøyesen P, Olsen I, Lend K, Hørslev-Petersen K, Uhlig T, Sokka-Isler T, Grondal G, Krabbe S, Lindqvist J, Gjertsson I, Glinatsi D, Kapetanovic M, Aga A, Faustini F, Parmanne P, Lorenzen T, Giovanni C, Back J, Hendricks O, Vedder D, Rannio T, Grenholm E, Ljoså M, Brodin E, Lindegaard H, Söderbergh A, Rizk M, Hermansson E, Larsson P, Uhrenholt L, Just S, Stevens D, Bay Laurberg T, Bakland G, Haavardsholm E, Lampa J. An Investigator-initiated Multicenter Randomized Study in Early Rheumatoid Arthritis of Active Conventional Therapy versus Three Biological Treatments: 48 Week Clinical and Radiographic Results of the NORD-STAR Trial [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/an-investigator-initiated-multicenter-randomized-study-in-early-rheumatoid-arthritis-of-active-conventional-therapy-versus-three-biological-treatments-48-week-clinical-and-radiographic-results-of-the/. Accessed .

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