Early Intensification of Treatment Induces Superior Outcomes in Two Randomized Trials According to Predicted Vs. Observed Radiographic Progression in Rheumatoid Arthritis

Adrian Levitsky¹, Marius C. Wick², Timo Möttönen³, Marjatta Leirisalo-Repo⁴, Leena Laasonen⁵, Hannu Kautiainen^6,7, Markku Korpela⁸, Ronald F. van Vollenhoven¹ and Vappu Rantalaiho⁸, ¹Department of Medicine, Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID), The Karolinska Institute, Stockholm, Sweden, ²Radiology, Karolinska University Hospital, Stockholm, Sweden, ³Internal Medicine, Division of Rheumatology, Turku University Central Hospital, Turku, Finland, ⁴Rheumatology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland, ⁵Helsinki Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland, ⁶Unit of Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland, ⁷Unit of Primary Health Care, Kuopio University Hospital, Kuopio, Finland, ⁸Department of Internal Medicine, Center for Rheumatic Diseases, Tampere University Hospital, Tampere, Finland

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: anti-TNF therapy, DMARDs, Early Rheumatoid Arthritis, prognostic factors and radiography

Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Predicted vs. Observed Radiographic Progression in early Rheumatoid Arthritis (POPeRA) is a method that has previously confirmed the relative radiographic efficacy of synthetic disease-modifying antirheumatic drugs (DMARDs) and anti-TNF treatment (1, 2). Here, we applied the POPeRA technique to the randomized Finnish Rheumatoid Arthritis Combination trial (3) (FIN-RACo, combination vs. single) as well as the NEO-RACo trial (4) (combination+anti-TNF vs. combination+placebo) in order to demonstrate how various treatment modalities affect radiographic progression.

Methods:

POPeRA utilizes the baseline radiographic score divided by the patient-reported symptom duration in months before baseline to predict radiographic outcomes over time, and simulates how patients would progress as if not on treatment. It was applied to 144 and 90 patients with eRA from the FIN-RACo and NEO-RACo trials, respectively. The Larsen score (FIN-RACo) and Sharp-van der Heijde score (SHS) (NEO-RACo) was available at baseline, 2, and 5 years. For FIN-RACo, patients were randomized either to a single DMARD (all starting with sulfasalazine; 60% had prednisolone in accordance to the physician’s judgment) or to more intensive DMARD combination therapy (all starting with triple therapy: methotrexate+sulfasalazine+hydroxychloroquine with prednisolone). In NEO-RACo, all patients were assigned to FIN-RACo combination protocol plus a randomized 6-month induction of either placebo or anti-TNF treatment (infliximab). For both trials, treatment became unrestricted after 2 years.

Results:

In FIN-RACo, combination vs. single therapy 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, n=72, respectively). Patients positive for rheumatoid factor (RF) (n=102) had significantly worse changes from predicted at 2 and 5 years than RF-negative patients (n=42) (-13.6 vs. 38.1, p=0.035; -6.7 vs. 44.3, p=0.002, respectively). Superiority for combination vs. single therapy was observed in both RF-positive and RF-negative patients.

In NEO-RACo, combination+6-month anti-TNF therapy (n=44) led to significantly greater reductions from predicted progression than combination+placebo (n=46) 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). However, anti-TNF add-on treatment was superior only among RF-positive patients (n=67).

Conclusion:

These results confirm that conventional combination therapy in eRA has a

long-term radiographic benefit versus monotherapy. Using the POPeRA method, the addition of anti-TNF induction therapy for 6 months was shown to further increase the long-term radiographic benefit in RF-positive patients.

References:

1. Wick MC, et al. Ann Rheum Dis. 2005;64:134–7.

2. Levitsky A, et al. Scand J Rheumatol. 2015 May 20:1-6. [Epub ahead of print].

3. Möttönen T, et al. Lancet. 1999 May 8;353(9164):1568-73.

4. Leirisalo-Repo M, et al. Ann Rheum Dis. 2013 Jun;72(6):851-7.

Disclosure: A. Levitsky, None; M. C. Wick, None; T. Möttönen, Abbvie, Amgen, BMS, Eli Lilly, MSD, Pfizer, Roche, 5; M. Leirisalo-Repo, Abbvie, Boehringer Ingelheim, BMS, MSD, Pfizer, Regeneron, Roche, 5; L. Laasonen, Abbvie, Pfizer, MSD, VTT (Technical Research Centre of Finland Ltd.), 5; H. Kautiainen, None; M. Korpela, None; R. F. van Vollenhoven, AbbVie, BMS, GSK, Pfizer, Roche, UCB, 2,AbbVie, Biotest, BMS, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, Vertex, 5; V. Rantalaiho, Orion-Farmos Research Foundation, 2,Abbvie, BMS, GSK, Pfizer, MSD, Roche, UCB Pharma, 5.

To cite this abstract in AMA style:

Levitsky A, Wick MC, Möttönen T, Leirisalo-Repo M, Laasonen L, Kautiainen H, Korpela M, van Vollenhoven RF, Rantalaiho V. Early Intensification of Treatment Induces Superior Outcomes in Two Randomized Trials According to Predicted Vs. Observed Radiographic Progression in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/early-intensification-of-treatment-induces-superior-outcomes-in-two-randomized-trials-according-to-predicted-vs-observed-radiographic-progression-in-rheumatoid-arthritis/. Accessed .

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