Despite rapid reductions in C-reactive protein (CRP) levels after ustekinumab therapy in psoriatic arthritis (PsA), baseline T-helper (Th)17-associated cytokine levels and CRP were not predictive of patients’ therapeutic response to ustekinumab, according to research results published in Arthritis and Rheumatology.
Researchers used data from 927 participants across 2 phase 3 clinical trials (PSUMMIT 1 [ClinicalTrials.gov identifier NCT01009086] and PSUMMIT 2 [ClinicalTrials.gov identifier NCT01077362]) to evaluate the association between CRP and circulating Th17-associated cytokines with PsA disease activity and patient response to ustekinumab therapy.
Both PSUMMIT studies included patients with active PsA who received 45 mg or 90 mg ustekinumab or placebo at baseline, week 4, and every 12 weeks until the conclusion of the study. The primary endpoint for both studies was the proportion of patients with 20% improvement in American College of Rheumatology response criteria (ACR20) at 24 weeks.
In the current study, researchers measured concentrations of interleukin (IL)-17A, IL-17F, IL-23, and CRP in samples collected during the PSUMMIT studies. Post hoc analyses measured the relationships of IL-17A, IL-17F, and CRP at baseline, week 4, and week 24 and measured IL-23 at baseline only.
Researchers found that baseline serum levels of IL-17A and IL-17F were positively correlated with clinical skin disease scores, measured via body surface area and psoriasis area severity index (PASI); correlations ranged from r = 0.39 to r = 0.62. Similar correlations of IL-23 with body surface area and PASI were also noted but to a lesser degree (r = 0.31 and r = 0.26, respectively).
Serum CRP levels were not significantly correlated with either joint (r = 0.04) or skin disease (r = 0.19) activity at baseline, and no significant correlations were noted between cytokines and baseline joint disease activity, measured via swollen (r = −0.04) and tender joint (r = 0.18) counts.
Similar analyses were made to examine the association of baseline serum levels for all markers with clinical response at 24 weeks. No significant associations were found with baseline levels of IL-17A, IL-17F, CRP, or IL-23, regardless of how the response was measured (skin improvement via percentage of patients who have achieved a ≥50% [PASI50] or ≥75% [PASI75] reduction in their PASI score from baseline or joint symptom improvement via ACR20 responders vs nonresponders). This finding was noted in both the ustekinumab and placebo arms.
In both PSUMMIT trials, patients who received ustekinumab therapy showed a statistically significant reduction in baseline levels of IL-17A, IL-17F, and CRP at week 4 (P <.05); geometric mean decreases ranged from 24% to 44% in IL-17A, 27% to 38% in IL-17F, and 18% to 35% in CRP.
In addition, decreases in CRP were noted at week 24 in both trials: a significant difference from changes noted in the placebo arm (P <.05).
Finally, investigators found that among all patients treated with ustekinumab, CRP decreased from baseline levels in both patients who achieved PASI75 and nonresponders (defined as persons who did not achieve PASI50); however, the reduction was significantly greater in the PASI75 group (geometric mean decreases, 58% vs 33% in PSUMMIT 1 and 51% vs 32% in PSUMMIT 2; P <.05).
Similarly, among patients treated with ustekinumab who achieved ACR20 response, significantly greater reductions in CRP were noted compared with ACR20 nonresponders.
One study limitation noted was the lack of data from additional therapeutics, which would indicate if these results are specific to ustekinumab therapy, or “more generic to IL-23 inhibition.”
“It will be interesting to observe changes in IL-23/[IL]-17 pathway cytokines in response to agents targeting this pathway via different routes… and how these correlate with clinical outcomes,” the researchers concluded.
Disclosures: This study was funded by Janssen Research and Development. Researchers who are current or former employees of Janssen Research and Development were involved in the study design, as well as data collection, analysis, and interpretation.
Siebert S, Sweet K, Dasgupta B, Campbell K, McInnes IB, Loza MJ. Serum CRP, IL-17A, and IL-17F levels are responsive to ustekinumab in psoriatic arthritis: lessons from the PSUMMIT study programme [published online May 9, 2019]. Arthritis Rheumatol. doi:10.1002/art.40921