Treat-to Target for Early RA Patients in Usual Clinical Practice, a Randomized Study with a Favorable Effect of a Second Oral Pulse of Prednisolone. the Amsterdam COBRA Treat-to-target Study

Linda Hartman¹, Linda Rasch², Samina Turk³, Marieke ter Wee¹, Pit Kerstens⁴, Conny van der Laken⁵, Mike Nurmohamed⁶, Dirkjan van Schaardenburg⁷, Lilian van Tuyl⁸, Alexandre Voskuyl¹, Maarten Boers⁷ and Willem Lems¹, ¹Amsterdam Rheumatology and Immunology Center, location Amsterdam UMC, VUmc, Amsterdam, Netherlands, ²Amsterdam Rheumatology and Immunology Center, location Amsterdam UMC, VUmc, Amsterdam, ³Amsterdam Rheumatology and Immunology Center, location Reade, Amsterdam, Netherlands, ⁴Westfriesgasthuis, Hoorn, Netherlands, ⁵Amsterdam Rheumatology and immunology Center, location Amsterdam UMC, VU medical center, Amsterdam, Netherlands, ⁶Amsterdam Rheumatology and immunology Center, location Reade and Amsterdam UMC, VU medical center, Amsterdam, Netherlands, ⁷Amsterdam Rheumatology and immunology Center | Reade and Amsterdam UMC, Amsterdam, Netherlands, ⁸Nivel, Utrecht, Netherlands

Meeting: ACR Convergence 2020

Keywords: Randomized Trial, rheumatoid arthritis

Session Information

Date: Monday, November 9, 2020

Title: RA – Treatments IV: New Therapies & Strategies (2008–2012)

Session Type: Abstract Session

Session Time: 5:00PM-5:50PM

Background/Purpose: EULAR guidelines advise to start with methotrexate (MTX) for early rheumatoid arthritis (RA), either alone or combined with prednisolone. Since this strategy is not effective in all patients after 13 weeks, we performed a randomized controlled trial to compare the effect of the addition of a second oral pulse of prednisolone versus continuation of MTX and prednisolone.

Methods: Newly diagnosed RA patients with symptom duration < 2 years were classified into a low- and high-risk group. High-risk patients either had DAS44 >3.7, or presented with at least 2 out of 3 unfavorable prognostic factors: CRP >10 mg/l; IgM RF or antiCCP with high titer; at least 1 erosion. The remaining patients were classified as low-risk. The treatment target was response (DAS44 < 1.6) or EULAR good response. Nonresponders at 13 weeks were randomized to treatment intensification or continuation, and the primary endpoint was % responders at 26 weeks.

Results: In total 189 patients were included. High-risk patients (n=150; mean age 51 years, 63% female, baseline DAS44 3.50, RF+ 75%, antiCCP+ 77%) were treated with COBRA-light (1, 2) (30 mg/day oral prednisolone, tapered in 8 weeks to 7.5 mg/day, and MTX increasing to 25 mg/week): 112 (75%) patients reached the treatment target at 13 weeks and 2 patients dropped out. On continued treatment, 92% of the responders retained the target. The 36 incomplete responders were randomized to treatment intensification with 60 mg/day prednisolone, tapered in 6 weeks to 7.5 mg/day, and addition of sulfasalazine 2000 mg/day and hydroxychloroquine 400 mg/day (COBRA-plus, n=17) or continuation (n=19). After 26 weeks the treatment target was met in 14 patients (82%) of the intensified group vs 9 (47%) of the control group (difference: 35%, [95%CI 6;64]; p=0.01).

The low-risk group (n=39; mean age 56 years, 59% female, baseline DAS44 2.66, RF+ 21%, antiCCP+ 26%) was treated with MTX monotherapy increasing to 25 mg/week: only 19 (49%) reached the target at week 13 and 4 patients dropped out. On continued treatment, 95% of the responders retained the target after 26 weeks. The 16 incomplete responders were randomized to treatment intensification with a COBRA-light oral pulse of prednisolone (n=9) or continuation (n=7). After 26 weeks the treatment target was met in 5 patients (56%) of the intensified group vs 3 (43%) in the control group (difference: 13%, [95%CI –36;62]; p=0.28).

1 den Uyl D, et al. Ann Rheum Dis 2014; 1071-8.
2 ter Wee M, et al. Ann Rheum Dis 2015; 1233-40.

Conclusion: With the COBRA-light strategy, 75% of RA patients with moderate to high disease activity or poor prognostic factors met the treatment target after 13 weeks. Remarkably, intensification at week 13 with added DMARDs and a second oral pulse of prednisolone even further improved the initial high response rate suggesting that patients not reaching the target at 13 weeks benefit from COBRA-plus. In the small low-risk group, only 49% met the treatment target after 13 weeks. Here, no effect of treatment intensification was found, possibly related to the small number of individuals. More treat-to-target trials are needed, particularly in patients with mild RA.

Disclosure: L. Hartman, None; L. Rasch, None; S. Turk, None; M. ter Wee, None; P. Kerstens, None; C. van der Laken, None; M. Nurmohamed, None; D. van Schaardenburg, None; L. van Tuyl, None; A. Voskuyl, None; M. Boers, None; W. Lems, None.

To cite this abstract in AMA style:

Hartman L, Rasch L, Turk S, ter Wee M, Kerstens P, van der Laken C, Nurmohamed M, van Schaardenburg D, van Tuyl L, Voskuyl A, Boers M, Lems W. Treat-to Target for Early RA Patients in Usual Clinical Practice, a Randomized Study with a Favorable Effect of a Second Oral Pulse of Prednisolone. the Amsterdam COBRA Treat-to-target Study [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/treat-to-target-for-early-ra-patients-in-usual-clinical-practice-a-randomized-study-with-a-favorable-effect-of-a-second-oral-pulse-of-prednisolone-the-amsterdam-cobra-treat-to-target-study/. Accessed .

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