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

Article Figures & Data

Download figure
Open in new tab
Download powerpoint
Figure 1.
Mean changes from baseline in DAS28-CRP over time in the phase IIa (A) and phase IIb (B) studies, and the proportions of patients achieving ACR20 response over time in the phase IIa (C) and phase IIb (D) studies. Phase IIa analyses used observed cases on treatment with LOCF of last visit before treatment failure, and phase IIb analyses used the mITT study population. ACR20: American College of Rheumatology ≥ 20% improvement; DAS28-CRP: 28-joint Disease Activity Score using C-reactive protein; LOCF: last observation carried forward; mITT: modified intent-to-treat.
Download figure
Open in new tab
Download powerpoint
Figure 2.
Treatment group differences in changes in DAS28-CRP from baseline to Week 12 by geographic region in the phase IIb study. DAS28-CRP: 28-joint Disease Activity Score using C-reactive protein; LS mean: least square mean.

Table 1.

Summary of adverse events for the phase IIa and phase IIb trials. Data are n (%) unless otherwise indicated.

	Phase IIa		Phase IIb		Phase IIb Toreforant
	Placebo	Toreforant, 100 mg	Placebo	3 mg	10 mg	30 mg	Combined, 30 mg^*
Safety population, n	28	58	68	67	68	68	87
Patients with AE	14 (50)	34 (59)	45 (66.2)	39 (58.2)	42 (61.8)	40 (58.8)	46 (52.9)
Common AE (≥ 5% of patients)
Nasopharyngitis	1 (4)	3 (5)	7 (10.3)	2 (3.0)	5 (7.4)	8 (11.8)	8 (9.2)
Urinary tract infection	—	—	2 (2.9)	4 (6.0)	4 (5.9)	5 (7.4)	5 (5.7)
Bronchitis	—	—	2 (2.9)	4 (6.0)	3 (4.4)	4 (5.9)	4 (4.6)
Diarrhea	—	—	1 (1.5)	2 (3.0)	1 (1.5)	8 (11.8)	8 (9.2)
Arthralgia	1 (4)	6 (10)	—	—	—	—	—
Back pain	0	4 (7)	—	—	—	—	—
RA, possible flare/worsening	1 (4)	3 (5)	—	—	—	—	—
Nausea	0	3 (5)	—	—	—	—	—
Patients who died	0	1 (2)	0	0	0	0	0
Patients with SAE	1 (4)	6 (10)	5 (7.4)	3 (4.5)	5 (7.4)	2 (2.9)	2 (2.3)
SAE occurring in > 1 patient	1 (4)	2 (3)	—	—	—	—	—
AE affecting dosing in phase IIa^**/leading to study agent discontinuation in phase IIb	4 (14)	6 (10)	5 (7.4)	6 (9.0)	3 (4.4)	3 (4.4)	3 (3.4)
AE occurring in ≥ 1 patient	—	—	1 (1.5)	2 (3.0)	1 (1.5)	0	0

↵* Includes 19 patients who early escaped from placebo, 3 mg, or 10 mg to receive 30 mg at Week 16.
↵** All AE affecting dosing in the phase IIa study each occurred in 1 single patient only. AE: adverse event; SAE: serious AE; RA: rheumatoid arthritis.