PARIS — For inflammatory dermatological diseases, the phenomenon of a “super response” to a biologic, meaning a rapid and near complete relief of symptoms and disease activity, predicts a higher likelihood of a sustained benefit, according to a growing body of long-term follow-up data.

Two new post hoc analyses of phase 3 trial studies — one with the interleukin (IL)-13 inhibitor tralokinumab in patients with atopic dermatitis and another with the IL-23 inhibitor guselkumab in patients with psoriasis — provide recent examples. But super responses have been reported for multiple treatments and multiple inflammatory diseases, not only those that affect the skin.

In a presentation devoted to super responses in patients with atopic dermatitis at European Academy of Dermatology and Venereology (EADV) 2025 Congress, Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, Oregon, listed an array of targeted therapies known to induce a super response, including inhibitors of IL-13 and IL-17.

No Single Super Response Definition Employed

It appears unlikely that a single definition of super response to biologics will be applicable across different mechanisms of action and different inflammatory diseases, but Simpson said this phenomenon has become an active area of research. Reliable predictors of a super response, better information about the prognostic impact of a super response, and strategies to elicit a super response are among goals of this research.

Examples were provided by several post hoc analyses at the EADV Congress. These involved super responders who emerged in the phase 3b GUIDE trial with guselkumab in patients with moderate-to-severe psoriasis and the phase 3 ECZTRA atopic dermatitis trial.

From the placebo-controlled GUIDE 3b trial, which generated several publications, including an evaluation of the impact of early intervention at week 28, two post hoc analyses of the 303 (34.4%) super responders were presented from the 880-patient trial. In one, the authors, led by Andreas Pinter, MD, PhD, University Hospital Frankfurt, Frankfurt am Main, Germany, compared outcomes at 68 weeks among those who started guselkumab after a short duration of disease (SDD), defined as < 24 months from symptom onset, with those who started therapy after a longer disease duration (LDD).

Super responders, defined as having achieved a Psoriasis Activity and Area Severity Index (PASI) score of 0 by week 20 were more common in the SDD group (43.7% vs 28.1%), suggesting this is a predictor of a super response. But the analysis further showed that the proportion of patients achieving PASI score ≤ 1 at 68 weeks was greater among SDD patients relative to LDD patients independent of a super response (85.1% vs 68.8%; P < .0001).

“Even within the super responder population, SDD patients showed greater clearance than LDD patients at week 68,” reported Pinter. These rates were 83.6% vs 75.7% for super responders and 43.6% vs 40.2% for nonsuper responders when SDD and LDD were compared.

“The advantage of treating psoriasis early is evidence in that both super responder and nonsuper responder populations benefited for receiving guselkumab within 2 years of symptom onset,” Pinter said.

In a second post hoc analysis, the impact of guselkumab withdrawal was explored in 273 super responders who remained clear (PASI score < 3) after 68 weeks (final dose was administered at 52 weeks). The duration of disease control was compared among those with an ultra-short SDD before initiating therapy (< 15 months), those with an intermediate duration (15-24 months), and those with LDD. Retreatment was permitted if disease recurred (PASI score > 5).

Psoriasis Cleared Off Therapy for Up to 3 Years

“Overall, 13 super responders remained treatment-free for more than 3 years following guselkumab withdrawal,” reported Knut Schäkel, MD, PhD, of the Department of Dermatology, Heidelberg University Hospital, Heidelberg, Germany.

Of these, 11 were in the ultra-short SDD group, one was in the intermediate group, and one was in the LDD group. This extended response off therapy suggests “guselkumab may have disease-modifying properties in a subset of patients, particularly those initiating treatment early in the disease course,” Schäkel reported.

Atopic Dermatitis Super Responder Data Reported

This same type of extended duration of benefit was also found to be more common among patients with atopic dermatitis who had a super response to tralokinumab in the ECZTEND open label extension trial. In this case, super response was defined as 90% clearance on the Eczema Area and Severity Index (EASI 90) by week 16.

At week 16, 33% of patients treated with tralokinumab achieved the study definition of a super response. In addition,15% achieved both an EASI 90 score and Dermatology Life Quality Index (DLQI) score of 0/1.

In this case, patients remained on therapy for long-term follow-up extending out to 120 weeks at which time 58.8% of the super responders maintained a stable response of EASI 90 score and DLQI score of 0/ 1, according to Andrew Blauvelt, MD, who left his previous academic position to conduct research as the principal of The Blauvelt Consulting firm, Annapolis, Maryland. He added that the rate was slightly higher for those with the greatest response, such as EASI score < 2, at week 16.

“These results may help clinicians predict long-term treatment success based on response after 16 weeks of tralokinumab treatment,” Blauvelt reported.

The potential for a super response to be a meaningful predictor of disease control and prognosis was a major point made by Simpson in his overview. He noted that super response data has so far largely been generated by post hoc analyses and case studies, but there are implications for understanding response to biologics at the individual level.

So far, it is difficult to draw broad conclusions about the clinical relevance of a super response beyond individual biologics for which these have been explored, but there appears to be a strong potential for this level of response to modify the course in the case of at least some biologics and in at least some inflammatory dermatologic diseases, according to Simpson. He indicated this is a hot area of ongoing research.

Simpson reported financial relationships with more than 35 pharmaceutical companies, several of which make biologics. Blauvelt reported financial relationships with more than 40 pharmaceutical companies, including Leo Pharma which provided funding for ECZTEND and his analysis. Pinter has financial relationships more than 30 pharmaceutical companies including Janssen-Cilag, which provided fundings for the GUIDE trial analysis. Schäkel reported no potential conflicts of interest.