Novel composite endpoint – Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS) – is feasible and well-balanced in assessing treatment efficacy in patients with Sjögren syndrome, according to study results published in The Lancet Rheumatology.
Previous studies conducted to assess the efficacy of potential treatment options for Sjögren syndrome have used the European Alliance of Associations for Rheumatology (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI). Although ESSDAI is a validated instrument, it measures only systemic disease activity. Several randomized controlled trials to assess the efficacy of various drugs in primary Sjögren syndrome, including rituximab, abatacept, and tocilizumab, have not met their primary endpoints (most often ESSDAI).
The objective of the current study was to develop a composite outcome measure for assessing treatment efficacy in patients with primary Sjögren syndrome. The CRESS is a comprehensive tool that includes a combination of disease activity and functional and serologic parameters.
A multidisciplinary team of researchers selected clinically relevant items to include in a composite endpoint. For each measurement, cutoff points for response to treatment were chosen based on expert opinion, previously published data on minimal clinically important improvements, and trial data.
Data from 3 multicenter, placebo-controlled trials of rituximab (Trial of Anti-B Cell Therapy in Patients With Primary Sjögren’s Syndrome [TRACTISS]), abatacept (multinational abatacept), and tocilizumab (Efficacy of Tocilizumab in Primary Sjögren’s Syndrome) were used to externally validate CRESS. The number and percentage of responders for separate CRESS items and total CRESS were calculated at week 48 for TRACTISS and at week 24 for the other 2 trials.
The CRESS consisted of 5 complementary, clinically relevant items, including systemic disease activity by Clinical ESSDAI; patient-reported symptoms by EULAR Sjögren’s Syndrome Patient Reported Index; tear gland item by Schirmer’s test and ocular staining score; salivary gland item assessed by unstimulated whole saliva and salivary gland ultrasonography; and serology assessed by rheumatoid factor and immunoglobulin G (IgG). Responses on at least 3 of 5 items provided the best distinction between treatment groups and was selected as the definition of total CRESS response.
Post hoc analysis of the trial data using the CRESS resulted in higher response rates among patients treated with abatacept and rituximab than in those treated with placebo. Total CRESS response rates among participants in the ASAP-III trial (ClinicalTrial.gov Identifier: NCT02067910) were 60% (n=24/40) for abatacept-treated patients and 18% (n=7/37) for placebo-treated patients (P <.0001). In the TRACTISS trial, total CRESS response rates were 49% (n=33/67) for rituximab vs 30% (n=20/66) for placebo (P =.026). Response rates were 45% (n=41/92) for abatacept vs 32% (n=30/95) for placebo (P =.067) in the multinational abatacept trial, and 18% (10 of 55) for tocilizumab vs 24% (n=13/55) for placebo (P =.48) in the Efficacy of Tocilizumab in Primary Sjogren’s syndrome trial.
The study had several limitations. The data were not available on sensitivity to change of the CRESS in patients with long-standing disease because they were not included in randomized controlled trials.
“This study is an important advance in the search for valid composite endpoints for use in future clinical trials of primary [Sjögren] syndrome,” the researchers wrote.
Arends S, de Wolff L, van Nimwegen JF, et al. Composite of relevant endpoints for Sjögren’s syndrome (CRESS): development and validation of a novel outcome measure. Lancet Rheumatol. Published online May 26, 2021. doi:10.1016/S2665-9913(21)00122-3