C-Reactive Protein Effective as Biomarker for HS Treated with Adalimumab

Alexa B. Kimball, MD, MPH

Credit: Beth Israel Deaconess Medical Center

Individuals with hidradenitis suppurativa (HS) and elevated serum C-reactive protein (CRP) will have a higher body mass index (BMI) and more severe disease, new findings suggest, and the efficacy of adalimumab may decrease among those with the most severe inflammatory load.¹

These findings were the conclusion of a recent post-hoc analysis of 2 clinical trials looking at CRP as a biomarker of systemic inflammation and of HS severity. The data was authored by Alexa B. Kimball, MD, MPH, from the Clinical Laboratory for Epidemiology and Applied Research in Skin at Beth Israel Deaconess Medical Center.

Kimball and her team of investigators noted that while family history and dermal tunnels may be supplemental content linked to timing and duration of patients’ adalimumab therapy responses, the identifying of biomarkers may help physicians determine treatment adjustments.²

“Although nonspecific, serum C-reactive protein (CRP) is an accessible marker of systemic inflammation that correlates with body mass index (BMI) (via the expression of interleukin 6 in adipose tissue) and Hurley stage,” wrote. “We tested whether CRP was associated with response to adalimumab in patients with HS.”¹

Background and Design

The data featured in this post-hoc analysis was the result of findings from a set of phase 3 randomized clinical studies known as PIONEER I and PIONEER II. In these analyses, investigators had assessed the individuals aged 18 - 69 years treated with adalimumab for their moderate to severe HS, examining the drug’s efficacy for HS.

From November 2011 - January 2014, the first study took place. From December 2011 - April 2014, the second trial had been conducted. Trial participants were randomized by the research teams of each study to be treated either with 40 mg of adalimumab each week or treated with a placebo, all of which occurred over a 12-week timeframe.

The PIONEER study team had evaluated any observable clinical improvement through the use of the HS clinical response at the conclusion of their research. In the latest post-hoc assessment of these findings, Kimball and colleagues included only the trial subjects who finished out the study and also had available laboratory data at both the point of baseline and at the 12-week mark.

The research team in the newest analysis defined CRP for patients involved in this research as levels exceeding 0.30 mg/dL, given the available trial protocol. The utilized statistical analyses that employed χ² tests for categorical variables, some of which included sex and race.

They also implemented Welch two-sample t-tests and Wilcoxon rank-sum tests. The investigators looked at the potential association between levels of CRP in patients and responses to adalimumab therapy using multivariable logistic regression, as well as a 2-sided P-value < .05 suggesting statistical significance.

Notable Findings

The post-hoc analysis concluded their recruitment with 588 participants of the prior trials having met their criteria for inclusion in the research. Subjects were noted as having a mean age 36.4 years and 65.5% were reported to be female.

The research team found that there were increased levels of CRP among 78.9% of the participants and normal levels among 21.1%. In their evaluation of patients with elevated levels of CRP, Kimball and colleagues concluded that the median level had been 1.23 mg/dL (interquartile range [IQR], 0.65–2.81 mg/dL).

By the post-hoc analysis’ conclusion, it was reported that those showing elevated CRP were found to have a higher mean BMI as opposed to subjects that were shown not to have increased levels of CRP (mean 34.1, SD 7.9 versus mean 28.6, SD 6.0; P < .001). The former group also were notably reported to have presented with more severe disease.

The investigators determined that there was an association between baseline CRP elevation and diminished odds of a clinical response achievement (odds ratio [OR], 0.53; 95% CI, 0.34–0.83). They added that adalimumab therapy was linked to greater odds of such a response in both those showing elevated levels of CRP (OR, 3.18; 95% CI, 2.13–4.81) and those reporting normal levels of CRP (OR, 2.25; 95% CI, 1.06–4.88).

Despite these data, Kimball’s team highlighted that among those with increased baseline CRP being treated with the medication, it was found that each unit rise in patients’ level of CRP corresponded to slightly diminished odds of clinical response (OR, 0.99; 95% CI, 0.97–1.00).

If one assumes a linear relationship, the researchers determined that subjects showing a baseline CRP of 2.81 mg/dL had 30% decrease in odds of a response versus subjects with a baseline CRP level of 0.30 mg/dL (OR, 0.70; 95% CI, 0.49–0.97).

“Our findings suggest that adalimumab may be less effective in patients with the most severe inflammatory load,” they wrote. “When treating nonresponders, clinicians may consider weight-based dosing of adalimumab, checking drug levels, or trialing alternative biologics.”¹

References

1. ^{Gunter SJ, Porter ML, Kimball AB. C-Reactive Protein and Response to Adalimumab in Patients With Hidradenitis Suppurativa: A Post Hoc Analysis of 2 Randomized Clinical Trials. JAMA Dermatol. Published online January 08, 2025. doi:10.1001/jamadermatol.2024.5146.}
2. ^{Frew JW, Jiang CS, Singh N, et al. Dermal tunnels influence time to clinical response and family history influences time to loss of clinical response in patients with hidradenitis suppurativa treated with adalimumab. Clin Exp Dermatol. 2021;46(2):306-313.doi:10.1111/ced.14448.}