medwireNews: Belimumab, a B-lymphocyte stimulator specific inhibitor used for the treatment of systemic lupus erythematosus (SLE), has a stable safety profile over 8 years of follow-up, with no new safety signals observed, report researchers.
Outlining the rationale for the study, Ronald van Vollenhoven (Amsterdam Rheumatology and Immunology Center, the Netherlands) commented that “some medications have increasing toxicities with time,” but “what you would like to see with a drug is at least a flat line in terms of adverse events and that is actually what is happening here.”
He added that in fact there is a slight decrease, but acknowledged that this “is probably due to a certain selection of patients,” whereby patients with side effects stop taking treatment and are no longer followed up.
The efficacy of belimumab (10 mg/kg intravenously or 200 mg subcutaneously) was demonstrated for the treatment of SLE in two phase III studies in 2011, comparing it with standard of care. Participants in these two studies – BLISS-52 and BLISS-76 – were then able to continue open-label treatment with the drug.
A total of 733 patients from these studies plus five from a phase II study comparing intravenous belimumab 1 mg/kg against placebo participated in this extension study and all received intravenous belimumab 10 mg/kg.
The modified intention-to-treat group included 735 patients who were treated for over 8 years, amassing 3352 patient–years of data. Van Vollenhoven did point out, however, that 41.1% of this group initially received placebo in the parent BLISS studies.
As reported at the 2018 EULAR meeting in Amsterdam, there was no increase in adverse events, serious adverse events, or events resulting in discontinuation.
Headache was the most common adverse events, affecting 27.9% of patients, and among the 18.8% of patients with a grade 3 or 4 event, thrombocytopenia (1.1%) and lupus nephritis (1.0%) were the most common.
Serious infections remained low and stable, at 14.6%, and the death rate was “very, very low,” said van Vollenhoven, at 1.5%, with just one of the 11 deaths (cardiogenic shock) thought to be possibly related to belimumab treatment.
Van Vollenhoven focused on some adverse events of particular interest. Infusion reactions occurred sometimes, but he said that the rate “is fortunately very low,” at 16.6% “and certainly decreases quite strongly with time.” Infection rates were also stable or improving.
He highlighted a consistent decrease in the incidence of psychiatric events, with a low rate of serious depression, occurring in four (0.5%) patients. And there were just 0.4% of cases of attempted suicide or self-harm and no completed suicides, which van Vollenhoven said provided some reassurance that the concern raised in the initial studies that long-term belimumab may be associated with suicidality, “does not play out over time.”
The incidence of malignancies remained very low, occurring in just eight (1.1%) patients and with no increase over the 8 years of follow-up.
Organ damage progression was minimal, with only 4.9% of patients after 1 year experiencing a 1-point increase on the SLICC Damage Index (SDI) and just 0.6% more than 2 points.
“With time […], the proportion of patients who did not have any additional damage accruing was very high and remained almost 90% over the entire follow-up,” reported van Vollenhoven.
He added that this was also true for patients with low complement levels or those who tested positive for double stranded DNA antibodies and may therefore have been at greater risk for damage.
Similarly, according to baseline disease activity on the Safety of Estrogens in Lupus Erythematosus National Assessment–SLE Disease Activity Index (SELENA–SLEDAI), patients with high activity, scoring at least 10 points, had a little bit more damage than those with low activity (score of 9 or below), but the “vast majority” did not have an increase in points on the SDI.
Van Vollenhoven concluded that the findings provide “some important information.”
By Lucy Piper
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