medwireNews: Findings from the phase 3 ASAP-III trial indicate that abatacept does not significantly improve disease activity relative to placebo among patients with primary Sjögren’s syndrome.
Hendrika Bootsma (University Medical Center Groningen, the Netherlands) and co-investigators report that average improvements in EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score over 24 weeks were not significantly different among the 40 participants who were randomly assigned to receive once-weekly subcutaneous abatacept 125 mg compared with the 39 patients who were instead given placebo.
Specifically, the median ESSDAI score decreased from 14 points at baseline to approximately 8 points at week 24 in the abatacept group, and from 13 to approximately 8 points in the placebo arm, with a nonsignificant between-group difference of 1.3 points after adjustment for baseline values and previous DMARD use.
“On the basis of our results, and considering the high cost of abatacept, we cannot recommend the use of abatacept as standard of care to alleviate systemic disease activity in patients with primary Sjögren’s syndrome,” write Bootsma and team in The Lancet Rheumatology.
Nonetheless, the ASAP-III (Abatacept Sjögren Active Patients phase III) investigators did observe some advantages with abatacept. For example, the Female Sexual Function Index score at week 24 was significantly better among women given abatacept versus placebo (adjusted mean difference=3.8 points), which they say “might be important, considering the negative effect of primary Sjögren’s syndrome on sexual function.”
Median ESSDAI scores at week 12 were also significantly lower in the abatacept versus placebo arm (adjusted difference=2.4 points), but Bootsma and team note that there was no significant between-group difference in the proportion of patients reaching the minimal clinically important improvement of at least 3 points.
They report that abatacept was well tolerated, with no deaths or unexpected serious adverse events (AEs) occurring in either group. A total of 95% of patients in each arm experienced AEs of any severity, while moderate AEs occurred in 8% of the abatacept group and 18% of the placebo group, and severe AEs were reported in 3% and 8%, respectively.
Discussing the ASAP-III results in an accompanying comment, Benjamin Fisher (University of Birmingham, UK) says that histologic data from the trial are “eagerly awaited,” but in light of previous open-label study results showing “no change in any histological parameters” with abatacept, he says that “abatacept might simply lack efficacy in Sjögren’s syndrome.”
He writes: “Unless future analyses reveal clear histological improvement or subgroups enriched for abatacept response, it is hard to see a way forward for abatacept in Sjögren’s syndrome.”
However, the commentator notes that abatacept, a T-cell co-stimulation inhibitor, “targets only one of many immune co-stimulation pathways,” and “[g]iven the importance of T-cell activation and B-cell-to-T-cell interactions in Sjögren’s syndrome, these alternative pathways should be actively explored” in future studies.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature group
Lancet Rheumatol 2020; doi:10.1016/S2665-9913(19)30160-2
Lancet Rheumatol 2020; doi:10.1016/S2665-9913(20)30002-3