Background Certolizumab pegol (CZP) significantly improved signs and symptoms of RA in a diverse group of patients, including 37.6% who previously used a TNF inhibitor.1
Objectives To evaluate short-term non-contrast low-field MRI for predicting long-term efficacy of CZP in patients with moderate to severe active RA who failed at least one non-biologic or biologic DMARD.
Methods In this 2-center open-label study, 20 adult RA pts with DAS > 4.4, on stable dose of MTX, received CZP 400 mg at week (wk) 0, 2 and 4, followed by 200 mg every two wks for 52 wks. All patients had unilateral hand and wrist non-contrast MRI using 0.2 T extremity unit at baseline, 6wk, 16wk and 52wk. The images were scored according to the RAMRIS system and 9-point cartilage loss (CL) scale by a radiologist blinded to visit order.
Results Baseline patients’ characteristics were as follows: Mean (SD) age 52.2 (16.9) years old, 70% female, Mean (SD) disease duration 7.3 (5.6) years, 50 % of pts were RF+, 60% anti-CCP+. Mean (SD) MTX dose was 17.25 (3.0) mg/week, Prednisone 2.5 (5.0) mg, 85% of pts were previously on a biologic. Tender/Swollen Joint Count (out of 68/66) was 34/16. Mean (SD) HAQ 4.38 (1.68), DAS28 6.60 (1.06), DAS28CRP 5.74 (0.66). 16/20 pts completed 52 wks.
No serious adverse events were reported in this patient population. DAS28 and RAPID scores were significantly reduced at wks: 6, 12, 16, 24, 40, 48 and 52 compared with baseline (Wilcoxon; p<0.001). ACR20/50/70 response rates at 16 & 52 wks (with non-completers considered as non-responders) were 60/30/15 & 45/30/20 %, respectively. At wk 12, 80% and at wk 52, 69% of pts achieved moderate or good EULAR response. Only two pts achieved low disease activity (DAS<3.2) at wk 52. 80% of patients had a DAS28 improvement of ≥ 1.2 by week 12. Of these, 25% did not achieve EULAR response at wk 52. None of the remaining 20% of pts with DAS28 improvement < 1.2 by wk 12, had a EULAR response at wk 52.
52-wk EULAR responders had significantly higher improvement in the OST scores at 16 wks, as compared to non-responders (p= 0.043). Changes in SYN, ERO or CL scores did not differ substantially between the two groups (Figure 1). All pts who improved their OST scores by wk 16, were clinical responders at wks 12 and 52.
12-wk clinical responders had 73% probability of EULAR response at wk 52, but if they also had 16-wk OST improvement, the probability was 100% (PPV=1.0). Conversely, if OST worsened, the probability of achieving EULAR response at 52 wks was only 33% (NPV = 0.66).
Conclusions In this preliminary study of an active RA population who failed at least one DMARD and included 85% of pts who previously used a biologic, improvement of osteitis on MRI predicted long-term clinical response to CZP. This finding may be particularly significant in determining therapeutic choices in patients with RA who have previously used a biologic. Our observations were based on a small patient population and suggest a trend without statistical relevance. Larger studies should be done to confirm these findings.
Weinblatt ME, et al. Rheumatol. 2012;
Østergaard M, et al. J Rheumatol. 2003;
Peterfy C, et al. Arthritis Res Ther. 2012
Disclosure of Interest E. Olech Grant/research support from: Abbvie, Genentech, Pfizer, UCB, Vertex, Consultant for: Abbvie, Janssen, Pfizer, UCB, Speakers bureau: Abbvie, UCB, C. Peterfy Shareholder of: Spire Sciences, LLC, Grant/research support from: Amgen, Centocor / Janssen, Pfizer / Wyeth, Abbott, Roche, Genentech, Bayer, Consultant for: Abbott, Articulinx, Merck/ Schering-Plough, Roche, UCB, Pfizer / Wyeth, AstraZeneca, Bristol Myers-Squibb, BioClinica, Celgene, Genentech, Icon Medical Imaging, Lilly, Medimmune, Moximed, Novartis, Perceptive Informatics, VirtualScopics, Jannsen, Genzyme/Sanofi, Biogen-Idec, Employee of: Spire Sciences, LLC, J. DiCarlo Consultant for: Abbott, Amgen, AstraZeneca, BioClinica, Biogen-Idec, Bristol-Myers Squibb, Celgene, Centocor, Core Lab Partners, Crescendo, Eli Lilly, Genentech, Genzyme, Icon Medical Imaging, Johnson & Johnson, Merck, Novartis, Perceptive Informatics, Pfizer, Rigel, Roche, Sanofi, Samsung, UCB, VirtualScopics, Wyeth, Employee of: Spire Sciences, LLC, J. Sagliani: None Declared, A. Genovese: None Declared, N. Gaylis Grant/research support from: Genentech Roche, BMS, UCB, Consultant for: UCB, Speakers bureau: Janssen, UCB