Treatment of hidradenitis suppurativa with adalimumab in the PIONEER I and II randomized controlled trials reduced indices of systemic inflammation, recognized risk factors for cardiovascular disease.

Abstract

Background: Hidradenitis suppurativa (HS) is associated with increased cardiovascular disease (CVD) risk. Systemic immune inflammation index (SII), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are biomarkers of systemic inflammation and CVD. One small study identified a lower NLR and PLR in patients treated with adalimumab (ADA).

Objectives: To assess changes in SII, NLR, PLR and MLR in a larger cohort and to evaluate their association with disease severity and treatment response.

Methods: This was a post hoc analysis of PIONEER I (ClinicalTrials.gov ID: NCT01468207) and PIONEER II (ClinicalTrials.gov ID: NCT01468233), two phase III randomized placebo-controlled clinical trials of ADA for HS. SII, NLR, PLR and MLR were log10-transformed and a linear mixed model was used to estimate the treatment effect.

Results: SII, NLR, PLR and MLR decreased from baseline levels with ADA treatment by week 12, when the primary response endpoint was assessed. Significant changes first appeared at week 4 and were maintained to week 36. In contrast, no significant changes were observed in placebo-treated patients. In patients re-randomized at week 12 from placebo to ADA, SII, NLR, PLR and MLR also reduced within 4 weeks. In patients re-randomized from ADA to placebo, these biomarkers returned to baseline by week 36. In addition, SII, NLR and PLR correlated with draining fistula count (r = 0.26-0.43, P < 0.001). ADA nonresponders in PIONEER I had a higher SII, NLR and PLR at baseline and week 12, but this change did not achieve statistical significance when draining fistulae were adjusted for.

Conclusions: Treatment of patients with HS with ADA resulted in rapid sustained reduction in systemic inflammation, measured by the biomarkers SII, NLR, PLR and MLR, which correlate with CVD risk. SII, NLR and PLR may predict ADA response, although this may be dependent on their interaction with the number of draining fistulae.