(National Institutes of Health)
31 March 2016. A late-stage clinical trial shows a small-molecule drug reduces pain and inflammation in patients with rheumatoid arthritis, who stopped responding to earlier protein treatments. A report of the study testing the drug baricitinib, made by Eli Lilly & Company that sponsored the trial, appears in today’s issue of New England Journal of Medicine (paid subscription required).
Rheumatoid arthritis is an autoimmune disease, where the immune system is tricked into attacking healthy cells, that leads to inflammation of joints — wrists, fingers, feet, and ankles — and surrounding tissue, affecting some 1.3 million people in the U.S. making it the most prevalent autoimmune disease. About three-quarters of those with the disease are women. Since the late 1990s, injectable engineered protein therapies showed promise in relieving rheumatoid arthritis symptoms, but for as many as 20 percent of people taking those biologics, the treatments stop working or cause adverse side effects.
Baricitinib is among a class of small-molecule, or low molecular weight, drugs known as Janus kinase or JAK inhibitors that block the actions of enzymes interrupting the immune system. Limiting the pathway for signals from JAK enzymes helps treat autoimmune diseases like rheumatoid arthritis, by reducing the signals that encourage inflammation. The drug is designed to be taken as a once-a-day pill.
The clinical trial tested baricitinib in two dosages — 2 and 4 milligrams — as well as against a placebo given daily for 24 weeks, among 527 participants with moderate to severe rheumatoid arthritis, who experienced the disease for an average of 14 years. Participants in the study also had previously taken 1 or more biologic treatments that stopped working. The study took place at 178 sites in 24 countries, including Stanford University, where immunologist Mark Genovese was one of the senior authors.
The study team used a standard measure of pain, inflammation, and disability developed by American College of Rheumatology, or ACR, as the main indicator of effectiveness, with a minimum threshold of 20 percent improvement. The results show 55 percent of participants taking the 4 milligram dose achieved 20 percent or more improvement on the ACR scale after 12 weeks, as did 49 percent of those taking the 2 milligram dose, compared to 27 percent receiving the placebo. Larger numbers of participants taking baricitinib also showed improvements of 50 and 70 percent on the standard ACR scale, compared to those taking the placebo.
Genovese says in a university statement that baricitinib appears to work across the patient population, despite individual medical histories and prior drugs. “The drug worked well across all patient subgroups,”notes Genovese, “independently of what they’d been taking before or how long they’d had the disease.”
Adverse effects rates were somewhat higher among participants taking baricitinib (71% to 77%) than those receiving the placebo (64%). The most common adverse effects were common cold, headache, and upper respiratory infections. Serious adverse effects were reported in 10 percent of the higher dose baricitinib recipients, compared to 7 percent of those taking the placebo, and 4 percent of those receiving the lower baricitinib dose. One death, from a stroke, occurred among the higher dose baricitinib recipients.
Lilly is conducting four more late-stage trials of baricitinib, including a study in China. The drug is under regulatory review in both Europe and the U.S.
Read more:
- Trial Shows Immunotherapy Reduces Rheumatoid Arthritis
- Spin-Off Biotech Formed for Autoimmune Disorders
- Lilly Acquiring Treatment for Autoimmune Disorders
- Biosimilar Shown Effective for Rheumatoid Arthritis
- Autoimmune Therapy Developer Raises $23M in Early Funds
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