PMID- 28118538 OWN - NLM STAT- MEDLINE DCOM- 20170814 LR - 20180119 IS - 2326-5205 (Electronic) IS - 2326-5191 (Linking) VI - 69 IP - 5 DP - 2017 May TI - Peficitinib, a JAK Inhibitor, in Combination With Limited Conventional Synthetic Disease-Modifying Antirheumatic Drugs in the Treatment of Moderate-to-Severe Rheumatoid Arthritis. PG - 932-942 LID - 10.1002/art.40054 [doi] AB - OBJECTIVE: To evaluate the efficacy and safety of orally administered once-daily peficitinib in combination with limited conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with moderate-to-severe rheumatoid arthritis (RA). METHODS: In this randomized, double-blind, phase IIb trial, patients with RA (n = 289) were treated with peficitinib 25 mg, 50 mg, 100 mg, or 150 mg or matching placebo once daily for 12 weeks. The primary end point was the percentage of patients who met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 12. RESULTS: ACR20 response rates at week 12 were 22.0%, 36.8%, 48.3% (P < 0.05), 56.3% (P < 0.01), and 29.4% in the peficitinib 25 mg, 50 mg, 100 mg, 150 mg, and placebo groups, respectively. Patients in the peficitinib 100 mg and 150 mg groups achieved a rapid and statistically significant ACR20 response compared with those in the placebo group (P < 0.05), reaching statistical significance by week 2. Overall, the incidence of adverse events (AEs) was similar between patients receiving peficitinib and those receiving placebo. The most common AEs were upper respiratory tract infection (5% [n = 15]), nausea (4% [n = 12]), and urinary tract infection (4% [n = 10]). There was 1 case of herpes zoster in the placebo group, and 1 serious infection (limb abscess) in the peficitinib 25 mg group. There were no incidences of grade 2 or higher neutropenia or lymphopenia. CONCLUSION: In patients with moderate-to-severe RA, orally administered once-daily peficitinib in combination with limited csDMARDs resulted in a dose-dependent ACR20 response rate over 12 weeks with satisfactory tolerability. CI - (c) 2017, American College of Rheumatology. FAU - Genovese, Mark C AU - Genovese MC AD - Stanford University, Palo Alto, California. FAU - Greenwald, Maria AU - Greenwald M AD - Desert Medical Advances, Palm Desert, California. FAU - Codding, Christine AU - Codding C AD - Health Research of Oklahoma, Oklahoma City. FAU - Zubrzycka-Sienkiewicz, Anna AU - Zubrzycka-Sienkiewicz A AD - ARS Rheumatica, Warsaw, Poland. FAU - Kivitz, Alan J AU - Kivitz AJ AD - Altoona Center for Clinical Research, Duncansville, Pennsylvania. FAU - Wang, Annie AU - Wang A AD - Astellas Pharma Global Development, Northbrook, Illinois. FAU - Shay, Kathyjo AU - Shay K AD - Astellas Pharma Global Development, Northbrook, Illinois. FAU - Wang, Xuegong AU - Wang X AD - Astellas Pharma Global Development, Northbrook, Illinois. FAU - Garg, Jay P AU - Garg JP AD - Astellas Pharma Global Development, Northbrook, Illinois. FAU - Cardiel, Mario H AU - Cardiel MH AD - Centro de Investigacion Clinica de Morelia SC, Morelia, Mexico. LA - eng SI - ClinicalTrials.gov/NCT01565655 PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Arthritis Rheumatol JT - Arthritis & rheumatology (Hoboken, N.J.) JID - 101623795 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Antirheumatic Agents) RN - 0 (Glucocorticoids) RN - 25X51I8RD4 (Niacinamide) RN - 3XC8GUZ6CB (Sulfasalazine) RN - 4QWG6N8QKH (Hydroxychloroquine) RN - 886U3H6UFF (Chloroquine) RN - EC 2.7.10.2 (Janus Kinase 3) RN - HPH1166CKX (peficitinib) RN - PJY633525U (Adamantane) SB - IM MH - Adamantane/administration & dosage/*analogs & derivatives/therapeutic use MH - Adult MH - Aged MH - Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use MH - Antirheumatic Agents/*administration & dosage/therapeutic use MH - Arthritis, Rheumatoid/*drug therapy MH - Chloroquine/therapeutic use MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - Glucocorticoids/*therapeutic use MH - Humans MH - Hydroxychloroquine/therapeutic use MH - Janus Kinase 3/*antagonists & inhibitors MH - Male MH - Middle Aged MH - Niacinamide/administration & dosage/*analogs & derivatives/therapeutic use MH - Severity of Illness Index MH - Sulfasalazine/therapeutic use MH - Treatment Outcome EDAT- 2017/01/25 06:00 MHDA- 2017/08/15 06:00 CRDT- 2017/01/25 06:00 PHST- 2016/04/15 00:00 [received] PHST- 2017/01/17 00:00 [accepted] PHST- 2017/01/25 06:00 [pubmed] PHST- 2017/08/15 06:00 [medline] PHST- 2017/01/25 06:00 [entrez] AID - 10.1002/art.40054 [doi] PST - ppublish SO - Arthritis Rheumatol. 2017 May;69(5):932-942. doi: 10.1002/art.40054.