These phenotypes were employed to individualize therapy with the currently available targeted bDMARDs. Patients with a Th1-predominant phenotype received ustekinumab (Stelara), which blocks the p40 subunit of interleukin (IL)-12 and IL-23. Patients with a Th17-predominant phenotype received secukinumab (Cosentyx), which targets IL-17. Patients with the Th1/Th17-high phenotype received either secukinumab or a tumor necrosis factor inhibitor. Patients with the Th1/Th17-low phenotype received a TNF inhibitor.
The 26 patients whose bDMARD therapy was individualized were compared with 38 PsA patients who received bDMARDs selected according to EULAR recommendations. The groups were similar for baseline characteristics.
In both groups, there were significant decreases from baseline in essentially all clinical measures, including the Simplified Disease Activity Index, the Psoriasis Area and Severity Index, and the Patient Global Health Assessment. However, several disease markers suggested greater disease control in those receiving individualized therapy. For example, the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) at 6 months was 0.76 in the Th17-predominant group versus 1.32 in those on an unselected bDMARD therapy (P = .008).
As a proportion of lymphocytes, Th1-predominant cells greater than 1.2% and Th17-predominant cells greater than 1.5% appeared to be sensitive cutoffs for predicting response to ustekinumab and secukinumab, respectively, according to data presented by Dr. Miyagawa. Although the results in this small series of patients are considered preliminary, Dr. Miyagawa said, “We think that this research is the first step toward the future use of precision medicine in PsA.”
Larger studies are needed to verify that lymphocyte phenotyping is an effective and reproducible strategy for individualizing selection of bDMARDs, but Dr. Miyagawa acknowledged other practical barriers to routine clinical application of this strategy. In particular, he called flow cytometry, which was employed in this study to phenotype lymphocyte expression, “complicated” for routine clinical use. However, this study strongly suggests that lymphocyte expression is a predictor of response to the different bDMARDs now available for treatment of PsA.
“The bDMARDs effective in PsA have different targets and may not offer the same degree of efficacy in all patients. Our study suggests an approach to optimal drug selection,” he said.
The study was not industry funded. Dr. Miyagawa reported no relevant financial disclosures.
