Biomarker May Flag Humira Responders in Hidradenitis Suppurativa

Serum level of inflammatory marker C-reactive protein (CRP) predicted response to adalimumab (Humira) treatment for patients with hidradenitis suppurativa, post hoc analysis of the PIONEER I and II trials found.

At 12 weeks of follow-up, adults with elevated CRP (defined as >0.30 mg/dL) at baseline — whose disease was also more severe — had lower odds of clinical response (OR 0.53, 95% CI 0.34-0.83), according to Alexa B. Kimball, MD, MPH, of the Beth Israel Deaconess Medical Center in Boston, and colleagues.

“Our findings suggest that adalimumab may be less effective in patients with the most severe inflammatory load,” the authors concluded in their research letter in JAMA Dermatology.

The drug still worked in patients with elevated baseline CRP, with 3.18-fold higher odds of response that was similar to the 2.25-fold increased odds seen in those with normal CRP as compared with placebo. However, among those with elevated CRP at baseline, the likelihood of clinical response decreased with each unit increase in CRP (OR 0.99, 95% CI 0.97-1.00). Assuming linearity, clinical response was 30% less likely for those with levels in the top quartile (≥2.81 mg/dL) than at the threshold for elevated CRP.

Noting that “rates of biologic failure remain substantial,” researchers suggested that “identifying biomarkers may help clinicians decide on an initial biologic or when to escalate therapy.”

Although nonspecific, serum 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 Kimball and co-authors.

The findings align with clinical experience, suggested Danilo C. Del Campo, MD, of the Chicago Skin Clinic, who was not involved in the study. The condition “often correlates with systemic inflammation and obesity, making CRP a logical marker for predicting treatment response,” he said.

“However, while CRP can reflect disease severity and systemic inflammation, I have not routinely used it as a decisive factor for initial dosing in practice. My standard approach is to initiate adalimumab at the FDA-approved dose regardless of baseline CRP or BMI and reassess based on clinical response after 12 weeks,” Del Campo told MedPage Today.

Steve Daveluy, MD, of Wayne State University in Detroit, agreed that there is no standard practice yet for response prediction.

“Predicting response to any treatment for [hidradenitis suppurativa] is nearly impossible, and I usually let patients know that response is unpredictable,” Daveluy told MedPage Today. “Another study showed that higher levels of monocytes in the blood correlated with a decreased likelihood of responding to adalimumab. These early studies help point us in the direction to learn more, but the data aren’t quite ready for us to put into practice.”

In terms of what to do when patients don’t respond to adalimumab, the researchers noted, “clinicians may consider weight-based dosing of adalimumab, checking drug levels, or trialing alternative biologics.”

Daveluy said he often combines biologics with spironolactone (in females), finasteride, metformin, zinc gluconate, or vitamin D, and also uses antibiotics for flares or sometimes long-term subantimicrobial dosing.

“Since CRP is associated with higher BMI, it may be interesting to see if these patients [with high CRP] are better candidates for metformin or maybe even GLP-1 agonists,” he noted. However, “CRP may be a predictor of more resistant disease that is unlikely to respond to other treatments as well.”

The study included 588 patients with moderate to severe hidradenitis suppurativa (65% women, mean age 36) who completed the PIONEER studies. Patients had been randomly assigned to receive adalimumab at 40 mg/week or placebo for 12 weeks. While the authors noted that hidradenitis suppurativa disproportionately affects Black patients, the analysis comprised just 13% of Black patients.

At baseline, 79% of participants had elevated CRP (average 1.23 mg/dL), and 21% had normal CRP. Mean BMI in those respective groups was 34.1 versus 28.6 (P

Study limitations included that the post hoc analysis was not part of the original study design. Further prospective research is needed to identify the point at which patients are unlikely to benefit from adalimumab therapy, researchers said.

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