Early treatment intensification induces favourable radiographic outcomes according to predicted versus observed radiographic progression in early rheumatoid arthritis: a subanalysis of the randomised FIN-RACo and NEO-RACo trials.
OBJECTIVE
Predicted versus observed radiographic progression in early rheumatoid arthritis (POPeRA) was applied to demonstrate how various treatment modalities affect and potentially minimise radiographic progression over time.


METHODS
The POPeRA method utilises the baseline radiographic score and patient-reported symptom duration to predict radiographic outcomes. It was applied at baseline, 2, and 5 years to patients with eRA from the randomised Finnish RA Combination trial (FIN-RACo) (n=144) and New Finnish RA Combination Therapy (NEO-RACo) (n=90) trials. For FIN-RACo, patients were randomised either to a single DMARD (sulfasalazine, with or without prednisolone) or to combination therapy (methotrexate+sulfasalazine+hydroxychloroquine, i.e. triple therapy, with prednisolone). In NEO-RACo, all patients were assigned intensified combination therapy (including 7.5 mg prednisolone/day) plus a randomised 6-month induction of either placebo or anti-TNF treatment (infliximab).


RESULTS
In FIN-RACo, combination versus monotherapy resulted in superior outcomes in the change from predicted progression over 2 and 5 years (mean 35.7% reduction vs. -32.9%, a worsening from predicted, p=0.001; 34.2% vs. -17.8%, p=0.003, respectively). In NEO-RACo, combination+anti-TNF induction led to significantly greater reductions from predicted progression than combination+placebo, both at 2 and 5 years of follow-up (98.5% vs. 83.4%, p=0.005; 92.4% vs. 82.5%, p=0.027, respectively). Importantly, anti-TNF add-on led to superior reductions from predicted among RF-positive patients (2 years: 97.4% vs. 80.4%, p=0.009; 5 years: 90.2% vs. 80.1%, p=0.030), but not among RF-negative patients.


CONCLUSIONS
These results confirm that conventional combination therapy in eRA has a long-term radiographic benefit versus monotherapy. Through POPeRA, it was made evident that anti-TNF induction therapy for 6 months further increases the long-term radiographic benefit of combination therapy in RF-positive patients.
Department of Medicine, Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID), Karolinska Institutet, Stockholm, Sweden.
Adrian
A
Levitsky
Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
Marius C
MC
Wick
Division of Rheumatology, University of Turku and Turku University Central Hospital, Finland.
Timo
T
Möttönen
Department of Medicine, Division of Rheumatology, University of Helsinki and Helsinki University Hospital, Finland.
Marjatta
M
Leirisalo-Repo
Helsinki Medical Imaging Center, University of Helsinki, Finland.
Leena
L
Laasonen
Department of Internal Medicine, Centre for Rheumatic Diseases, Tampere University Hospital, Finland.
Markku
M
Korpela
Department of Medicine, Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID), Karolinska Institutet, Stockholm, Sweden; and Amsterdam Rheumatology and Immunology Centre ARC, the Netherlands.
Ronald F
RF
van Vollenhoven
Department of Internal Medicine, Centre for Rheumatic Diseases, Tampere University Hospital; and School of Medicine, University of Tampere, Finland.
Vappu
V
Rantalaiho
D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D012074:Remission Induction; D012460:Sulfasalazine / Q000627:therapeutic use; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D011239:Prednisolone; D008727:Methotrexate