2011: More Meticulously Following Treat-to-target in RA Does Not Lead to Less Radiographic Progression: A Longitudinal Analysis in BIODAM

Sofia Ramiro¹, Robert Landewé², Désirée van der Heijde³, Alexandre Sepriano⁴, Oliver FitzGerald⁵, Mikkel Østergaard⁶, Joanne Homik⁷, Ori Elkayam⁸, Carter Thorne⁹, Maggie Larche¹⁰, Gianfranco Ferraccioli¹¹, Marina Backhaus¹², Gilles Boire¹³, Bernard Combe¹⁴, Thierry Schaeverbeke¹⁵, Alain Saraux¹⁶, Maxime Dougados¹⁷, Maurizio Rossini¹⁸, Marcello Govoni¹⁹, Luigi Sinigaglia²⁰, Alain Cantagrel²¹, CF Allaart¹, Cheryl Barnabe²², Clifton O. Bingham III²³, Dirkjan van Schaardenburg²⁴, HIlde Hammer²⁵, Rana Dadashova²⁶, Edna Hutchings²⁶, Joel Paschke²⁶ and Walter P Maksymowych²⁷, ¹Leiden University Medical Center, Leiden, Netherlands, ²Amsterdam University Medical Center, Meerssen, Netherlands, ³Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Leiden, Netherlands, ⁴Leiden University Medical Centre, Portela Loures, Portugal, ⁵Conway Institute, University College Dublin, Dublin, Ireland, ⁶Rigshospitalet, University of Copenhagen, Glostrup, Denmark, ⁷Division of Rheumatology, University of Alberta, Edmonton, AB, Canada, ⁸Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, ⁹Southlake Regional Health Centre, Newmarket, ON, Canada, ¹⁰McMaster University, Hamilton, ON, Canada, ¹¹Catholic University of the Sacred Heart, Rome, Roma, Italy, ¹²Park-Klinik Weissensee Academic Hospital of the Charité, Berlin, Germany, ¹³Universite de Sherbrooke, Sherbrooke, QC, Canada, ¹⁴CHU Montpellier and Montpellier University, Monpellier, France, ¹⁵FHU ACRONIM, University Hospital of Bordeaux, University of Bordeaux, Bordeaux, France, ¹⁶CHU Brest, Brest, France, ¹⁷Department of Rheumatology, Hôpital Cochin, Paris, France, Paris, France, ¹⁸Rheumatology Unit, Department of Medicine, University of Verona, Verona, Italy, ¹⁹S. Anna Hospital and University of Ferrara, Ferrara, Italy, ²⁰Gaetano Pini Institute, Milano, Italy, ²¹CHU Toulouse, Paul Sabatier University, Toulouse, France, ²²University of Calgary, Calgary, AB, Canada, ²³Johns Hopkins University, Baltimore, MD, ²⁴Amsterdam UMC, Amsterdam, Netherlands, ²⁵Diakonhjemmet Hospital, Oslo, Oslo, Norway, ²⁶CARE Arthritis LTD, Edmonton, AB, Canada, ²⁷Department of Medicine, University of Alberta, Edmonton, AB, Canada

Background/Purpose: A Treat-to-Target approach (T2T) is broadly considered to lead to better clinical outcomes and recommended in patients with RA. However, very few studies have analyzed the effect of T2T on radiographic progression, and any such studies have provided inconsistent results. Our aim was to investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice leads to lower radiographic progression in RA.

Methods: Patients from the multicenter RA-BIODAM cohort with ≥2 consecutive visits with radiographs available were included. In RA-BIODAM patients were enrolled as they were initiating a new csDMARD/bDMARD treatment were followed-up with the intention to benchmark and intensify treatment. The primary outcome of this analysis was the change in Sharp-van der Heijde score (SvdH, 0-448), assessed every 6 months, using average scores from 2 readers (scores with known chronological order). Following a DAS44-T2T remission strategy, which was defined at each 3-month visit, was the main variable of interest. Patients were categorized based on the proportion of visits in which T2T was followed according to our definition: very low (≤40% of the visits, low ( >40%, < 62.5%), high (≥62.5%, ≤75%) and very high ( >75%). Radiographic progression at 2 years was visualized across groups by cumulative probability plots. Per 3-month interval T2T could be followed zero, one or two times (in a total of 2 visits). Associations between the number of visits with T2T in an interval and radiographic progression, both in the same and in the subsequent 6-month interval, were analysed by generalised estimating equations, adjusted for age, gender, disease duration and country.

Results: In total, 511 patients were included (mean (SD) age: 56 (13) years; 76% female). After 2 years, patients showed on average 2.2 (4.1) units progression (median:1 unit). Mean (SD) 2-year progression was not significantly different across categories of T2T: very low: 2.1 (2.7)-units; low: 2.8 (6.0); high: 2.4 (4.5), very high: 1.6 (2.2) (Figure). Meticulously following-up T2T in a 3-month interval neither reduced progression in the same 6-month interval (parameter estimates (for yes vs no): +0.15 units (95%CI: -0.04 to 0.33) for 2 vs 0 visits; and +0.08 units (-0.06;0.22) for 1 vs 0 visits) nor did it reduce progression in the subsequent 6-month interval (Table).

Conclusion: In this daily practice cohort, more meticulously following T2T principles did not result in more reduction of radiographic progression than a somewhat more liberal attitude toward T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.
Figure 1: Cumulative probability plot with 2-year radiographic progression according to the proportion of 3-monthly visits with T2T followed

Table 1: Effect of following DAS44-remission-T2T strategy on 6-month radiographic progression over 2 years
Disclosures: S. Ramiro, AbbVie/Abbott, Eli Lilly, Galapagos, Merck/MSD, Novartis, Pfizer, UCB, Sanofi; R. Landewé, Abbott, Amgen, AstraZeneca, BMS, GSK, Novartis, Merck, Pfizer, Schering-Plough, UCB Pharma; D. van der Heijde, AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Novartis, Pfizer, UCB, Imaging Rheumatology bv, Lilly; A. Sepriano, UCB, Novartis; O. FitzGerald, Novartis, UCB, Bristol-Myers Squibb(BMS), Pfizer Inc, Eli Lilly, AbbVie, Janssen; M. Østergaard, AbbVie/Abbott, Amgen, Bristol-Myers Squibb(BMS), Celgene, Eli Lilly, Janssen, Gilead, Novartis, Pfizer, UCB; J. Homik, AbbVie/Abbott, Amgen, Pfizer, Janssen, Merck/MSD; O. Elkayam, Pfizer, Eli Lilly, AbbVie/Abbott, Novartis, Janssen, Boehringer-Ingelheim; C. Thorne, AbbVie/Abbott, Amgen, Celgene, CaREBiodam, Centocor, Janssen, Eli Lilly, Novartis, Pfizer, Sanofi, Medexus/Medac, Merck; M. Larche, None; G. Ferraccioli, None; M. Backhaus, None; G. Boire, AbbVie/Abbott, Bristol-Myers Squibb(BMS), Janssen, Eli Lilly, Merck/MSD, Novartis, Orimed Pharma, Pfizer, Samsung Bioepis, Teva, Viatris, Amgen, Celgene; B. Combe, AbbVie/Abbott, Bristol-Myers Squibb(BMS), Celltrion, Galapagos, Gilead, Janssen, Eli Lilly, Merck/MSD, Novartis, Pfizer, Roche; T. Schaeverbeke, None; A. Saraux, None; M. Dougados, Novartis, AbbVie, Eli Lilly, Merck, Pfizer, UCB Pharma; M. Rossini, Theramex, UCB, Amgen, AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Novartis, Pfizer Inc, Sandoz; M. Govoni, None; L. Sinigaglia, None; A. Cantagrel, AbbVie/Abbott, Amgen, Biogen, Bristol-Myers Squibb(BMS), Janssen, Eli Lilly, Médac, Merck/MSD, Novartis, Pfizer; C. Allaart, None; C. Barnabe, Janssen, Fresenius Kabi, Celltrion Healthcare, Pfizer; C. Bingham III, AbbVie, Janssen, Pfizer, Sanofi, Bristol Myers Squibb, Eli Lilly; D. van Schaardenburg, None; H. Hammer, None; R. Dadashova, None; E. Hutchings, None; J. Paschke, None; W. Maksymowych, AbbVie, Boehringer-Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB, CARE Arthritis Limited.