Pragmatic Multicenter Open-Label Randomized Controlled Trial of Stopping TNF-Inhibitors in Rheumatoid Arthritis Patients in Remission or Stable Low Disease Activity in the Netherlands

Marjan Ghiti Moghadam¹, Harald E. Vonkeman², Peter M. ten Klooster³, Janneke Tekstra⁴, Dirkjan van Schaardenburg⁵, Mirian Starmans-kool^6,7, Elisabeth Brouwer⁸, Reinhard Bos⁹, Willem F. Lems¹⁰, Edgar Colin¹¹, Cornelia F. Allaart¹², Inger L. Meek¹³, Robert B.M. Landewé¹⁴, Hein J. Bernelot Moens¹⁵, Piet van Riel¹³, Mart A.F.J. van de Laar¹⁶, Tim Jansen¹⁷ and on behalf of the Dutch National POET Collaboration., ¹rheumatology, Medisch Spectrum Twente - Arthritis Center Twente, Enschede, Netherlands, ²Ariensplein 1, Medisch Spectrum Twente - Arthritis Center Twente, Enschede, Netherlands, ³Pcgr, University of Twente, Enschede, Netherlands, ⁴Dept. Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands, ⁵Jan van Breemen Research Institute, Amsterdam, Netherlands, ⁶Rheumatology, Orbis Medical Center, Geleen-Sittard, Netherlands, ⁷Rheumatology, Atrium Medical center, Heerlen, Netherlands, ⁸Rheumatology, University Medical center Groningen, Groningen, Netherlands, ⁹Rheumatology, Medical Center Leeuwarden, Leeuwarden, Netherlands, ¹⁰Rheumatology, Amsterdam Rheumatology and immunology Center, VU University medical center, Amsterdam, Netherlands, ¹¹Rheumatology, Erasmus MC, Rotterdam, Netherlands, ¹²Department of Rheumatology, Leiden Universitary Medical Center, Leiden, Netherlands, ¹³Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, ¹⁴Department of Rheumatology, Amsterdam Rheumatology Center, Amsterdam, Netherlands, ¹⁵rheumatology, Ziekenhuisgroep Twente, Almelo, Netherlands, ¹⁶Rheumatology, Medisch Spectrum Twente - Arthritis Center Twente, Enschede, Netherlands, ¹⁷VieCuri Medical Center, Venlo, Netherlands

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: anti-TNF therapy, remission and rheumatoid arthritis (RA)

Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Clinical Aspects I - Treatment Advances and Strategies

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: TNF-inhibitors (TNFi) are effective treatments of rheumatoid arthritis (RA). It is not clear if patients in remission or stable low disease activity need to continue their TNFi. Issues of polypharmacy and the relatively high costs of TNFi make it important to examine whether patients in remission or stable low disease activity can stop their TNFi. If patients stop TNFi and consequently flare, it is unclear whether TNFi can be restarted effectively and safely.

Methods: Pragmatic multicenter open-label randomized controlled trial. Inclusion criteria: patients diagnosed with RA according to the ACR 1987 criteria, patients using a TNFi for at least 1 year with stable dose DMARDs over the last 6 months, DAS28 <3.2 over the last 6 months. Patients were randomized to either stop or continue their current TNFi in a 2:1 ratio. Flare was defined as DAS28 ≥3.2 with an increase ≥0.6 compared to the previous DAS28. In case of flare in the stop group, TNFi could be restarted at the discretion of the treating rheumatologist.

Results: In total 817 patients from 47 centers were included: 531 patients (65%) in the stop group and 286 patients (35%) in the continuation group. At 6 months, significantly more patients in the stop group (212/531 [31.5%]) had experienced a flare than in the continuation group (36/286 [9.8%], p<0.001). At 12 months these were 267/531 [50.3%] vs 52/286 [18.2%], respectively (p<0.001). The hazard ratio for flare after stopping TNFi was 3.41 (95% CI: 2.53–4.59). Mean DAS28 scores in the stop group were significantly increased throughout the follow-up period compared with the continuation group (p<0.001). Of the 195 patients that restarted TNFi within 26 weeks, 165 (84.6%) had regained low disease activity (DAS28 < 3.2) 6 months later and median time to regained low disease activity was 12 weeks (95% Cl: 10.8-13.2).

SAEs in stop vs. continuation groups: Deaths 0 vs. 1 (0.3%) and hospitalization due to infections 11 (2%) vs. 4 (1,4%), respectively. There were no allergic reactions among the patients in the stop group that restarted TNFi.

Conclusion: Stopping TNFi treatment in RA patients in remission or stable low disease activity results in substantially more flares than continuing.

Disclosure: M. Ghiti Moghadam, None; H. E. Vonkeman, None; P. M. ten Klooster, None; J. Tekstra, None; D. van Schaardenburg, None; M. Starmans-kool, None; E. Brouwer, None; R. Bos, Pfizer Inc, 2; W. F. Lems, None; E. Colin, None; C. F. Allaart, None; I. L. Meek, None; R. B. M. Landewé, None; H. J. Bernelot Moens, None; P. van Riel, None; M. A. F. J. van de Laar, None; T. Jansen, None.

To cite this abstract in AMA style:

Ghiti Moghadam M, Vonkeman HE, ten Klooster PM, Tekstra J, van Schaardenburg D, Starmans-kool M, Brouwer E, Bos R, Lems WF, Colin E, Allaart CF, Meek IL, Landewé RBM, Bernelot Moens HJ, van Riel P, van de Laar MAFJ, Jansen T. Pragmatic Multicenter Open-Label Randomized Controlled Trial of Stopping TNF-Inhibitors in Rheumatoid Arthritis Patients in Remission or Stable Low Disease Activity in the Netherlands [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/pragmatic-multicenter-open-label-randomized-controlled-trial-of-stopping-tnf-inhibitors-in-rheumatoid-arthritis-patients-in-remission-or-stable-low-disease-activity-in-the-netherlands/. Accessed .

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