Reasons for discontinuation
Overall, around a quarter of patients discontinued treatment with baricitinib, and “the reasons for this were lack of efficacy in approximately a quarter and adverse events in about two-thirds of the patients,” Dr. Edwards said.
Breaking down the types of adverse events was not part of this analysis, and that information is likely to come from the BSRBR-RA study team directly.
“We have some experience in our practice in Southampton,” Dr. Edwards observed. This experience was outlined in a separate abstract at the meeting and presented by Dr. May Nwe Lwin, a clinical research fellow within Dr. Edwards’ group.
Dr. Lwin presented data on 83 patients who had received baricitinib at University Hospital Southampton between October 2017 and July 2020, 55 (65.2%) of whom remain on treatment to date, with mean follow-up of 17 months. Of the 28 patients who stopped baricitinib, 21 stopped within 12 months.
“Patients who continued on baricitinib appeared more likely to be older and female,” Dr. Lwin said.
The mean age of patients who continued on treatment after 12 months was 61.5 years but was 49 years for those who stopped earlier. The percentage of women continuing treatment at 12 months versus those stopping earlier were a respective 82% and 67%. Both findings were significant (P < .001) but “could mean nothing, or could be very interesting data to explore more,” Dr. Lwin suggested.
“However, there was no significant difference in discontinuation rates for those using mono or combination therapy, and also no effect of disease duration or seropositivity,” Dr. Lwin said.
“Most people stopped baricitinib in the first 3 months of their treatment,” Dr. Lwin reported, noting that the most common reason was a lack of efficacy in 64% of patients, with 28.5% of patients discontinuing because of side effects.
“When you look at the adverse events, the reasons for discontinuation are quite variable,” Dr. Lwin said. These included infections (one urinary tract infection, two chest infections, and a urinary tract infection), and one case each of discitis, deranged liver function, lymphoma, and personality change.
Update on the long-term safety profile
Also at the BSR annual conference, an update on the long-term safety profile of baricitinib seen in clinical trials was presented, using data from the ‘All-BARI-RA’ dataset. This includes data from nine clinical trials and one long-term extension study.
“We recently published a long-term safety analysis of this molecule involving 3,700-plus patients with exposure up to 7 years,” said Kevin L. Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health Sciences University in Portland.
Dr. Winthrop provided an update on this, adding in another 13,148 patient-years of follow-up and giving data on the safety experience with baricitinib with up to 8.4 years of exposure for some patients.
“In short, not much has changed,” Dr. Winthrop said, noting that event rates have remained stable.
The overall major adverse cardiovascular event (MACE) and overall deep vein thrombosis/pulmonary embolism event rate were both 0.5 per 100 patient-years. Referring to the latter, Dr. Winthrop called them “rock solid stable” and “it’s been that way really all the way through the development program.”
Overall, event rates per 100 patient-years for serious infections, herpes zoster, and tuberculosis were a respective 2.7, 3.0, and 0.2. Serious infection rates over time have remained similar, but “clearly age is a risk factor for infection,” Dr. Winthrop said. “I would just say it’s similar to what we see with all biologics and small molecules in this setting.”
Malignancy and death rates were also higher in older patients, but after age adjustment, these had been stable across the different analysis points.
“Malignancy overall, excluding NMSC [nonmelanoma skin cancer], the event rate is 0.9 per 100 patient-years, very similar to what we’ve seen in the prior data cuts,” he said. “The same is true for lymphoma,” he added, with an overall event rate of 0.1 per 100 patient-years.
This updated analysis, Dr. Winthrop concluded, “suggests a safety profile really very similar to what was published recently.”Dr. Edwards has received research and educational grants and advisory panel and speaker fees from Eli Lilly and from multiple other pharmaceutical companies. The analysis of BSRBR-RA data he presented was sponsored by Eli Lilly and performed independently of the BSRBR-RA study team. Dr. Packham reported no conflicts of interest; he chaired the oral abstracts sessions in which Dr. Edwards presented his findings.
Dr. Lwin did not report having any disclosures.
Dr. Winthrop has acted as a consultant to Eli Lilly and several other pharmaceutical companies and had received research or grant support from Bristol-Myers Squibb and Pfizer. The work he presented was sponsored by Eli Lilly.