Kate Johnson

June 10, 2012

June 10, 2012 (Berlin, Germany) — Baricitinib, an investigational once-daily pill for the treatment of rheumatoid arthritis (RA) showed significantly better efficacy than placebo in a phase 2b trial presented at the European League Against Rheumatism (EULAR) Congress 2012.

The medication, being investigated by Eli Lilly & Co and Incyte Corp, is the second JAK1/JAK2 inhibitor under development for RA after Pfizer's twice-daily pill, tofacitinib, received preliminary approval last month from a US Food and Drug Administration advisory panel.

"This is really a paradigm shift if it works because…people have always wanted that holy grail of getting [once-daily] oral medicines," commented Christopher Buckley, MD, PhD, professor of rheumatology at the University of Birmingham, United Kingdom, and chairperson of the EULAR abstract selection committee. He was not involved with the study.

"It will also come down to cost," he continued in an interview with Medscape Medical News. "It is much cheaper to manufacture a small chemical entity like this than it is a biologic. The question will be where will it be positioned — whether you would go straight from methotrexate to these inhibitors and bypass the biologics — this is why it's going to be paradigm shifting."

The study, presented by lead author Edward Keystone, MD, from the University of Toronto, Canada, included 301 patients, mean age 51 years, with active RA on stable doses of methotrexate, who were randomly assigned to receive placebo or 1 of 4 doses of baricitinib (1 mg, 2 mg, 4 mg, or 8 mg) once daily.

A total of 76% of patients in the combined 4-mg and 8-mg baricitinib groups reached the primary outcome, the American College of Rheumatology 20 (ACR20, or a 20% improvement in tender/swollen joints) response at 12 weeks, compared with 41% of patients in the placebo group (P < .001).

"There were significant differences from placebo as early as 2 weeks," said Dr. Keystone during a press conference.

Similar statistically significant differences were seen for the secondary endpoints of ACR50 and ACR70.

Specifically, 35% of patients taking 4 mg and 40% of those taking 8 mg achieved an ACR50 response, compared with 10% of the placebo group; 23% of the 4 mg group and 20% of the 8 mg group achieved an ACR70 response, compared with 2% of the placebo group.

The rate of treatment-emergent adverse events was similar in the groups, with infections being the most common (12% in the placebo group vs 14% in the baricitinib group).

Seven serious adverse events were reported in 6 patients (2 events in the placebo group, 4 in the 2-mg group, and 1 in the 8-mg group). No deaths or opportunistic infections occurred in the active treatment groups.

"There is still a large proportion of patients that have inadequate responses to currently approved treatments for RA and baricitinib could represent a new, viable treatment option for this group of patients," said Dr. Keystone in a press release. "The JAK1/JAK2 signaling pathway has been shown to be important in the pathobiology of RA, and no other JAK1/JAK2 inhibitor treatments have been approved for the treatment of RA."

Asked how baricitinib compares with Pfizer's tofacitinib, Dr. Keystone hedged. "You can't directly compare. The efficacy and side-effects are within the same magnitude of what you see with tofacitinib."

Dr. Keystone receives grant and research support from Abbott Laboratories, Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, Centocor Inc, F. Hoffman-La Roche Inc, Genzyme Inc, Merck, Novartis Pharmaceuticals, Pfizer Pharmaceuticals , and UCB. He is a consultant for Abbott Laboratories, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Co, Centocor Inc, F.Hoffman-La Roche Inc, Genentech Inc, Merck, Nycomed, Pfizer Pharmaceuticals, and UCB. He is on the Speakers Bureau for Abbott Laboratories, Bristol-Myers Squibb, F.Hoffman-La Roche Inc, Merck, Pfizer Pharmaceuticals Inc, UCB, Amgen, and Janssen. Several of Dr. Keystone's coauthors are employees of Lilly and are sharefholders in the company. Dr. Buckley has disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2012. Abstract #LB0005. Presented June 8, 2012.

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