Toreforant, A Histamine H4 Receptor Antagonist, in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: Results of 2 Phase II Studies

J Rheumatol. 2016 Sep;43(9):1637-42. doi: 10.3899/jrheum.160164. Epub 2016 Jul 15.

Abstract

Objective: To assess toreforant (selective histamine H4 receptor antagonist) in active rheumatoid arthritis (RA).

Methods: In a phase IIa, double-blind, placebo-controlled test, 86 patients were randomized (2:1) to once-daily toreforant 100 mg or placebo for 12 weeks. In phase IIb, double-blind, placebo-controlled, dose-range-finding evaluations, 272 patients were randomized (1:1:1:1) to once-daily placebo or toreforant 3/10/30 mg. Primary efficacy endpoints for both studies were Week 12 changes in 28-joint Disease Activity Score-C-reactive protein (DAS28-CRP).

Results: Phase IIa testing was terminated prematurely (patient fatality; secondary hemophagocytic lymphohistiocytosis). Posthoc analyses indicated toreforant 100 mg/day reduced RA signs/symptoms through Week 12. Phase IIb testing, however, showed no significant Week 12 improvement in DAS28-CRP with toreforant.

Conclusion: Toreforant was not effective in phase IIb testing.

Keywords: CLINICAL TRIAL; HISTAMINE H4 RECEPTOR ANTAGONIST; METHOTREXATE; RHEUMATOID ARTHRITIS.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Histamine Antagonists / administration & dosage
  • Histamine Antagonists / adverse effects
  • Histamine Antagonists / therapeutic use*
  • Humans
  • Lymphohistiocytosis, Hemophagocytic / chemically induced
  • Methotrexate / therapeutic use
  • Receptors, Histamine H4 / antagonists & inhibitors*
  • Treatment Failure
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Histamine Antagonists
  • Receptors, Histamine H4
  • Methotrexate