1330: Certolizumab-pegol, Abatacept, Tocilizumab or Active Conventional Therapy in Early Rheumatoid Arthritis: 48 Week Patient-reported Outcomes of the NORD-STAR Trial

John Lampa¹, Dan Nordstrom², Ronald van Vollenhoven³, Merete Hetland⁴, Espen A Haavardsholm⁵, Mikkel Østergaard⁶, Anna Rudin⁷, Marte Schrumpf Heiberg⁵, Michael Nurmohamed³, Bjorn Gudbjornsson⁸, Kristina Lend⁹, Kim Hørslev-Petersen¹⁰, Tuulikki Sokka-Isler¹¹, Gerdur Maria Grondal¹², Simon Krabbe¹³, Joakim Lindqvist¹⁴, Anna-Karin Hultgård Ekwall¹⁵, Daniel Glinatsi¹⁶, Meliha Kapetanovic¹⁷, Cidem Gentline¹⁴, Anna-Birgitte Aga¹⁸, Heikki Relas², Tove Lorenzen¹⁹, Giovanni Cagnotto²⁰, Johan Back²¹, Oliver Hendricks²², Bas Dijkshoorn²³, Kajsa Öberg²⁴, Maud-Kristine Aga Ljoså²⁵, Eli Brodin²⁶, Hanne Merete Lindegaard²⁷, Annika Söderbergh²⁸, Milad Rizk²⁹, Alf Kastbom³⁰, Per Larsson³¹, Line Uhrenholt³², Søren Just³³, David J Stevens³⁴, Trine B Laurberg³⁵, Gunnstein Bakland³⁶, Inge Olsen³⁷, Joseph Sexton¹⁸ and Till Uhlig¹⁸, ¹Stockholm County, Hãsselby, Sweden, ²Helsinki University Hospital, Helsinki, Finland, ³Amsterdam University Medical Centers, Amsterdam, Netherlands, ⁴Copenhagen Center for Arthritis Research, Rigshospitalet, Copenhagen, Denmark, ⁵Diakonhjemmet Hospital, Oslo, Norway, ⁶Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet; University of Copenhagen, Copenhagen, Denmark, ⁷Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, ⁸Centre for Rheumatology Research, University Hospital, Reykjavik, Iceland, ⁹Amsterdam UMC, Karolinska Institute, Stockholm, Sweden, ¹⁰University of Southern Denmark, Odense, Denmark, ¹¹Jyvaskyla Central Hospital, Jyväskylä, Finland, ¹²Department for Rheumatology, Landspitali University Hospital, Reykjavik, Iceland, ¹³Herlev-Gentofte University Hospital, Herlev, Denmark, ¹⁴Karolinska University Hospital, Stockholm, Sweden, ¹⁵Department of Rheumatology and Inflammation research, Sahlgrenska Academy, University of Gothenburg, Kullavik, Sweden, ¹⁶Copenhagen Center for Arthritis Research, Rigshospitalet, Copenhagen, Sweden, ¹⁷Lund University and Skåne University Hospital, Lund, Sweden, ¹⁸Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway, ¹⁹Silkeborg University Hospital, Silkeborg, Denmark, ²⁰Skåne University Hospital, Lund, Sweden, ²¹Uppsala University Hospital, Uppsala, Sweden, ²²Danish Hospital for Rheumatic Diseases, Sønderborg, Denmark, ²³Amsterdam Rheumatology and Immunology Center, Location Reade, Amsterdam, Netherlands, ²⁴Falu Hospital, Falun, Sweden, ²⁵Ålesund Hospital, Ålesund, Norway, ²⁶Haukeland University Hospital, Bergen, Norway, ²⁷Odense Hospital, Odense, Denmark, ²⁸Örebro University Hospital, Örebro, Sweden, ²⁹Västmanlands Hospital Västerås, Västerås, Sweden, ³⁰Linköping University, Linköping, Sweden, ³¹Academic Specialist Center, Stockholm, Sweden, ³²Aalborg University Hospital, Aalborg, Denmark, ³³Section of Rheumatology, Department of Medicine, Odense University Hospital – Svendborg Hospital, Odense, Denmark, ³⁴St. Olavs Hospital, Trondheim, Norway, ³⁵Aarhus University Hospital, Aarhus, Denmark, ³⁶University Hospital of North Norway, Tromsø, Norway, ³⁷Oslo University Hospital, Oslo, Norway

Background/Purpose: The optimal first-line treatment of patients with early rheumatoid arthritis (eRA) is not established.

Methods: In this investigator-initiated, randomized, open-label study (NCT01491815), patients with treatment-naïve eRA with DAS28 >3.2 and RF+/ACPA+/CRP >10mg/L, were randomized 1:1:1:1 to methotrexate (MTX) combined with: 1) oral prednisolone (tapered quickly; discontinued at w36); or: sulphasalazine, hydroxy­chloroquine and mandatory intra-articular (IA) glucocorticoid injections in swollen joints (ACT); 2) certolizumab-pegol (CZP); 3) abatacept (ABA) or 4) tocilizumab (TCZ). IA glucocorticoid was allowed in all arms except during w20-24 and w44-48. The primary outcome Clinical Disease Activity Index (CDAI) remission and key secondary outcomes at 24 weeks have previously been published (Hetland ML et al, BMJ 2020;371:m4328). Differences between ACT and each of the 3 biological therapies for PRO (pain, patient´s global assessment, HAQ-DI, fatigue (VAS and FACIT) at 48 weeks were tested and descriptive data presented with 95% CI. Longitudinal data points were analyzed using a linear mixed model analysis. The continuous and dichotomous PRO data were adjusted for country, sex and anti-citrullinated protein antibody status. For continuous data, additional adjustment included baseline values of PRO endpoint and treatment arm and time as well as their interaction as categorical covariates. MCID for pain and fatigue were defined as: ≥ 10-point decrease for VAS pain (Strand V et al; J Rheumatol 2011;38;1720-7) and ≥10-point decrease for VAS Fatigue (Wells et al, J Rheumatol 2007:34(2);280-9), respectively.

Results: 812 patients were randomized. Baseline characteristics and adjusted baseline and 48-week PRO data are shown in table 1. In the longitudinal analysis there was a trend for greater improvement of pain and fatigue in biological groups compared to ACT (figure 1). Adjusted for baseline values, pain levels and physician global assessment were numerically lower in all biological groups compared to ACT at week 48. The percentage of patients reporting improvements above MCID for pain and fatigue (from baseline until 48 weeks) were numerically higher in biological arms compared to ACT (% and 95% CI), as follows: MCID for pain: ACT 68% (61, 74); CZP+MTX 77% (71, 82); ABA+MTX 80% (74, 85); TCZ+MTX 70% (64, 77); and for fatigue: ACT 55% (48, 62); CZP+MTX 62% (55, 69); ABA+MTX 63% (56, 69); TCZ+MTX 57% (59, 64) (figure 2).

Conclusion: All four different modes of action lead to marked improvements of PROs after 48 weeks. Compared with csDMARD+glucocorticoid treatment pain levels were lower in all biological arms at week 48. Likewise, the percentages of patients with clinically important improvements for pain and fatigue were numerically higher in the treatment arms with biological vs. conventional treatment.








J. Lampa: None; D. Nordstrom: AbbVie/Abbott, 2, BMS, 2, Lilly, 2, MSD, 2, Novartis, 2, Pfizer, 2, UCB, 2; R. van Vollenhoven: AbbVie, 2, 6, AstraZeneca, 2, 5, 6, Biogen, 6, Bristol-Myers Squibb(BMS), 2, 5, 6, Galapagos, 2, 5, 6, GlaxoSmithKline, 6, Janssen, 2, 6, MSD/Merck Sharp and Dohme, 5, Novartis, 5, Pfizer, 2, 5, 6, RemeGen, 2, Roche, 5, Sanofi, 5, UCB, 2, 5, 6; M. Hetland: AbbVie/Abbott, 1, 5, Bristol-Myers Squibb(BMS), 5, Danbio, 12, Chari of Danbio registry, Eli Lilly, 5, MEDAC, 6, Novartis, 5, Pfizer, 5, 6, Sandoz, 5, 6; E. Haavardsholm: None; M. Østergaard: AbbVie, 2, 5, 6, Amgen, 5, Boehringer-Ingelheim, 2, 6, Bristol-Myers Squibb(BMS), 2, 5, 6, Celgene, 2, 5, 6, Eli Lilly, 2, 6, Galapagos, 2, 6, Gilead, 2, 6, Hospira, 2, 6, Janssen, 2, 6, MEDAC, 6, Merck, 2, 5, 6, Novartis, 2, 5, 6, Novo Nordisk, 2, 6, Orion, 2, 6, Pfizer, 2, 6, Regeneron, 2, 6, Roche, 2, 6, Sandoz, 2, 6, Sanofi, 2, 6, UCB, 2, 6; A. Rudin: AstraZeneca, 12, financial support; M. Schrumpf Heiberg: Roche, 6; M. Nurmohamed: None; B. Gudbjornsson: Nordic-Pharma, 6, Novartis, 2, 6; K. Lend: None; K. Hørslev-Petersen: None; T. Sokka-Isler: None; G. Grondal: None; S. Krabbe: None; J. Lindqvist: None; A. Hultgård Ekwall: AbbVie/Abbott, 1, 2, Boehringer-Ingelheim, 6, Pfizer, 1; D. Glinatsi: Eli Lilly, 1, 6; M. Kapetanovic: None; C. Gentline: None; A. Aga: AbbVie, 2, 6, Eli Lilly, 2, 6, Novartis, 2, 6, Pfizer, 2, 6; H. Relas: None; T. Lorenzen: None; G. Cagnotto: Bristol-Myers Squibb(BMS), 5, UCB, 5; J. Back: None; O. Hendricks: AbbVie/Abbott, 6, Eli Lilly, 6, Novartis, 6, Pfizer, 6; B. Dijkshoorn: Galapagos, 2, Novartis, 2; K. Öberg: None; M. Ljoså: AbbVie/Abbott, 1, 12, Advisory board fee; E. Brodin: None; H. Lindegaard: None; A. Söderbergh: None; M. Rizk: None; A. Kastbom: None; P. Larsson: None; L. Uhrenholt: None; S. Just: None; D. Stevens: UCB, 1; T. Laurberg: None; G. Bakland: UCB, 2; I. Olsen: None; J. Sexton: None; T. Uhlig: Galapagos, 2, 6, Lilly, 2, 6, Novartis, 2, 6, Pfizer, 2, 6, UCB, 2, 6.