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Efficacy and safety of tregalizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase IIb, randomised, placebo-controlled trial

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van Vollenhoven RF1, Keystone EC2, Strand V3, Pacheco-Tena C4, Vencovský J5, Behrens F6, Racewicz A7, Zipp D8, Rharbaoui F8, Wolter R8, Knierim L8, Schmeidl R8, Zhou X8, Aigner S8, Dälken B8, Wartenberg-Demand A8; TREAT2b study team. Collaborators (99) Aelion J, Arreola JA, Arias MA, Back J, Baranauskaite A, Behrens F, Bennett R, Bookman A, Brzezicki J, Butrimiene I, Churchill M, Djacenko S, Dokoupilova E, Drescher E, Dudek A, Edwards W, Eliseeva L, Ershova O, Fortin I, Galatikova D, De la Torre IG, Garmish O, Gasanov Y, Gnylorybov A, Goldberg M, Golovchenko O, Gordeev I, Hiepe F, Sil GH, Husarova V, Iaremenko O, Jeka S, Kamburova D, Kavanaugh A, Keszthelyi P, Keystone E, Knyazeva L, Krechikova D, Kuzmanova S, Lapcikova A, Levinson D, Lopez Garcia JA, Lymar I, Marinova N, Moiseev S, Musilova L, Nagy M, Najam S, Nedovic J, Nemeth E, Novosad L, Ochoa-Ortega L, Oparanov B, Tena CP, Penev D, Pesant Y, Podrazilova L, Pulka G, Racewicz A, Raskina T, Rekalov D, Reshetko O, Riega Torres JC, Rubbert-Roth A, Rychlewska-Hanczewska A, Savina L, Schulze-Koops H, Bukilica MS, Shevchuk S, Simoncsics E, Simova L, Sitek-Ziolkowska K, Skublova A, Sliwowska B, Smakotina S, Spieler W, Stanislavchuk M, Stefanovic D, Stejfova Z, Stoilov R, Strapkova M, Stryuk R, Sulyok G, Sylwestrzak A, Szombati I, Theander J, Tomkova S, Trapp R, Tseluyko V, Tälli J, Vencovsky J, Vitek P, Vladeva S, Vo J, Vollenhoven RV, Vujasinovic-Stupar N, Wassenberg S, Wollenhaupt J, Zielinska A. Ann Rheum Dis. 2018 Jan 17. pii: annrheumdis-2017-212478. doi: 10.1136/annrheumdis-2017-212478. [Epub ahead of print]

Abstract

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1 Department of Rheumatology, Amsterdam Rheumatology and Immunology Center ARC, Amsterdam, The Netherlands.

2 The Rebecca MacDonald Centre For Arthritis, Mount Sinai Hospital, Toronto, Ontario, Canada.

3 Division of Immunology/Rheumatology, Stanford University School of Medicine, Palo Alto, California, USA.

4 Investigacion y Biomedicina de Chihuahua, Chihuahua, Mexico.

5 Institute of Rheumatology, Prague, Czech Republic.

6 Center for Innovative Diagnostics and Therapy in Rheumatology/Immunology (CIRI), Goethe University Frankfurt, Frankfurt, Germany.

7 ZDROWIE Osteo-Medic, Bialystok, Poland.

8 Biotest AG, Dreieich, Germany.

Abstract

OBJECTIVE: To evaluate the efficacy, biological activity and safety of tregalizumab in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX).

METHODS: 321 patients were randomised (1:1:1:1) to placebo or tregalizumab 25, 100 or 200 mg once-weekly subcutaneously in addition to MTX treatment. Responders at week 12 continued the same treatment, and non-responders at week 12 were escalated to the next higher tregalizumab dose level or re-randomised from placebo to active treatment. After 24 weeks, patients could continue treatment with tregalizumab for 24 weeks (extension phase). The primary endpoint was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. Safety and biological activity were monitored through week 48.

RESULTS: At week 12, ACR20 response rates were not statistically significantly different between placebo and any of the tregalizumab doses. Tregalizumab injections were well tolerated; most adverse events were mild to moderate and comparable among treatment and placebo groups. Biological activity was shown by dose-dependent CD4 downmodulation.

CONCLUSION: Treatment with tregalizumab did not show significant clinical efficacy in patients with active RA compared with placebo but resulted in the expected biological effect on CD4 modulation. Tregalizumab was generally well tolerated, and no new safety findings were identified.

TRIAL REGISTRATION NUMBER: NCT01999192; Results.