Dazodalibep safety
“Dazodalibep therapy was generally safe and well tolerated,” Dr. Baldini said in her presentation. Adverse events that were reported for both investigations were generally mild and occurred with similar frequency between the treatment groups. The most commonly reported adverse events, each occurring in more than 5% of patients who received dazodalibep, were COVID-19, diarrhea, anemia, dizziness, ligament sprain, upper respiratory tract infection, and nasopharyngitis. The incidence of COVID-19 and nasopharyngitis was comparable between the treatment and placebo arms.
However, in the patient group with moderate to high systemic disease activity, one patient who was treated with dazodalibep experienced two serious adverse events: a grade 3 SARS-CoV-2 infection, and subsequent death from an unknown cause, which occurred 46 days after the last administration of dazodalibep (12 days after COVID-19 diagnosis). Additionally, there was one case of herpes zoster in a patient treated with dazodalibep. In the group with limited systemic organ involvement, three serious adverse events were reported in the dazodalibep group (pneumonia influenza, postacute COVID-19 syndrome [long COVID], and gammopathy); one serious adverse event (neutropenia) was reported in the placebo group. One patient in the dazodalibep group discontinued participation in the study because of an adverse event, compared with two in the placebo group. Investigators determined that, thus far, all serious adverse events in both populations have been unrelated to the medication.
Throughout the trial, eligible participants in both populations were randomly assigned in a 1:1 ratio to receive either intravenous dazodalibep 1,500 mg or placebo every 2 weeks for three doses, followed by every 4 weeks for an additional four doses, up to day 169. The majority of participants in all populations and treatment arms were women (> 90%). Key inclusion criteria were being aged 18 years or older, meeting the 2016 American College of Rheumatology–EULAR classification criteria for Sjögren’s syndrome, and testing positive for anti-SSA and/or rheumatoid factors. Exclusion criteria were having a medical history of thrombosis or anticoagulant use, as well as prior treatment with B cell–depleting therapies. The proportions of patients who received glucocorticoids, antimalarials, or disease-modifying antirheumatic drugs were consistent between both arms of each population.
“Larger clinical trials are necessary to validate the clinical effectiveness and safety of dazodalibep therapy in this specific subgroup of patients,” Dr. Baldini concluded. Currently, dazodalibep is being studied for the treatment of rheumatoid arthritis and renal transplant rejection, and Horizon Therapeutics has plans to explore its use in focal segmental glomerulosclerosis.
Dr. Ng has served as a consultant to Novartis, GlaxoSmithKline, AbbVie, Bristol-Myers Squibb, Sanofi, MedImmune, Resolves Therapeutics, Janssen, and UCB. Dr. Baldini has served as a consultant to GlaxoSmithKline and Sanofi.
A version of this article first appeared on Medscape.com.