PACUPod is your trusted source for evidence-based insights tailored to advanced clinical pharmacists and physicians. Each episode dives into the latest primary literature, covering medication-focused studies across specialty pharmacy, and many more. We break down study designs, highlight key findings, and objectively discuss clinical implications—without the hype—so you stay informed and ready to apply new evidence in practice. Whether you’re preparing for board certification or striving for excellence in patient care, PACUPod helps you make sense of the data, one study at a time.
Britany: Welcome back to PACULit. Today, we are discussing the long-term efficacy and safety of secukinumab in moderate-to-severe hidradenitis suppurativa, focusing on the week one hundred four results from the SUNSHINE and SUNRISE extension trial. Seth, could you start by outlining the clinical problem this study addresses?
Seth: Certainly, Britany. Hidradenitis suppurativa, or HS, is a chronic inflammatory skin disease characterized by painful nodules, abscesses, and sinus tracts, primarily affecting intertriginous areas such as the axillae and groin. It affects approximately one percent of the population but is often underdiagnosed. The disease predominantly impacts young adults and females. HS causes significant pain, scarring, and recurrent flares, all of which substantially impair quality of life.
Britany: Treatment options for HS remain limited. Currently, adalimumab, a tumor necrosis factor alpha inhibitor, is the only approved biologic therapy, but its long-term efficacy varies among patients. The interleukin seventeen pathway plays a key role in HS pathogenesis, making secukinumab, an anti-interleukin seventeen A monoclonal antibody, a promising therapeutic candidate. Early phase three trials demonstrated positive results through fifty-two weeks.
Seth: The critical question has been the durability of secukinumab’s efficacy beyond one year and its safety profile during extended therapy. Additionally, optimal treatment duration and strategies for managing relapse after treatment withdrawal remain unclear. This extension trial was designed to evaluate secukinumab’s sustained efficacy and safety through one hundred four weeks in patients who initially responded.
Britany: To provide some context, the phase three randomized withdrawal extension enrolled adults with moderate-to-severe HS who had responded at week fifty-two in the SUNSHINE and SUNRISE parent studies. These responders were re-randomized in a one-to-one-to-one ratio to receive secukinumab three hundred milligrams every two weeks, every four weeks, or placebo.
Seth: The extension phase lasted until week one hundred four, providing two years of treatment exposure. The primary outcome was time to loss of response, defined as failure to maintain the Hidradenitis Suppurativa Clinical Response, or HiSCR. Secondary outcomes included the proportion of patients maintaining HiSCR and comprehensive safety assessments.
Britany: The investigators utilized Kaplan-Meier estimates to analyze time to loss of response and calculated hazard ratios comparing secukinumab dosing regimens to placebo. Subgroup analyses considered dosing frequency, prior biologic exposure, and baseline disease severity. The study maintained a double-blind design during the extension, with adherence monitored through clinic visits and patient diaries.
Seth: The patient population consisted of adults with moderate-to-severe HS who had demonstrated response at week fifty-two. Baseline characteristics were well balanced across groups, predominantly females in their early thirties, reflecting typical HS demographics.
Britany: Notably, many participants had prior biologic exposure, which is important since secukinumab’s efficacy appeared consistent regardless of previous treatments. Disease severity was moderate to severe, with extensive involvement of intertriginous areas and significant pain reported.
Seth: Pain reduction was sustained with secukinumab treatment, which is a meaningful benefit given the debilitating nature of HS-associated pain.
Britany: Turning to the key findings, the primary endpoint of time to loss of response was not met with statistical significance. However, there was a thirteen percent risk reduction for the every-two-week dosing and a thirty percent risk reduction for the every-four-week dosing compared to placebo.
Seth: Median time to loss of response was longer with secukinumab—two hundred eighty-three days for the every-two-week group and three hundred sixty-five days for the every-four-week group—versus two hundred thirty-nine and one hundred seventy-one days in the placebo groups, respectively. Continuing secukinumab therapy maintained clinical response for a longer duration.
Britany: Additionally, between thirty-four and fifty-eight percent of patients maintained HiSCR at the time of loss of response assessment. Patients switched to placebo experienced faster relapse, underscoring the importance of continuous treatment for many individuals.
Seth: Safety findings were consistent with prior data on secukinumab. No new safety concerns emerged during the extension. Adverse events were similar across treatment groups, and serious adverse events were rare, supporting the drug’s tolerability over the long term.
Britany: Clinically, secukinumab offers sustained benefits and a consistent safety profile in moderate-to-severe HS. Continuous therapy appears to reduce relapse risk, although some patients maintain response even after treatment withdrawal.
Seth: This variability reflects the heterogeneity of HS and highlights the need for personalized monitoring. Some patients may tolerate treatment interruptions, while others require ongoing therapy to maintain disease control.
Britany: The study’s strengths include its randomized withdrawal design and high retention rates, which lend credibility to the findings. Limitations include the primary endpoint not reaching statistical significance and the relatively short extension period for a chronic disease like HS.
Seth: The re-randomization to placebo complicates interpretation of durability. Additionally, the novel definition of loss of response may have reduced statistical power. Nevertheless, the use of clinically relevant HiSCR endpoints and thorough safety assessments are notable positives.
Britany: Related research includes the bimekizumab fifty-two-week trial, which targets both interleukin seventeen A and interleukin seventeen F, further reinforcing the role of the interleukin seventeen pathway in HS. The adalimumab open-label extension demonstrated durable response over one hundred sixty-eight weeks, providing a useful benchmark.
Seth: A recent meta-analysis confirmed secukinumab’s efficacy and tolerability through fifty-two weeks, emphasizing the need for longer-term data such as that provided by this trial. Collectively, these studies support interleukin seventeen inhibition as a viable long-term treatment strategy for HS.
Britany: From a clinical perspective, it is important to consider potential drug interactions. Secukinumab is generally well tolerated, but concomitant use of immunosuppressants may increase infection risk. Monitoring for infections is essential, especially in patients with comorbidities.
Seth: Special populations, including those with prior biologic exposure or different HS phenotypes, may respond variably to secukinumab. An exploratory analysis identified distinct phenotypes with differential responses, suggesting that disease characteristics influence treatment efficacy.
Britany: This insight could guide personalized treatment approaches. Patient-reported outcomes, such as pain reduction and quality of life improvements, should inform clinical decisions alongside objective lesion counts.
Seth: Given treatment variability, clinicians should tailor therapy duration and monitoring to individual patient needs, balancing efficacy, safety, and patient preferences.
Britany: Future research should aim to define optimal treatment duration and establish standardized criteria for loss of response. Identifying predictors of sustained response versus relapse would further optimize personalized HS therapy.
Seth: Comparative effectiveness studies between secukinumab and other biologics, such as adalimumab or bimekizumab, over longer periods would also aid clinical decision-making.
Britany: Before we conclude, Seth, what are your thoughts on how these findings might influence real-world clinical practice for hidradenitis suppurativa?
Seth: That is an excellent question, Britany. In real-world settings, clinicians often face challenges with patient adherence and managing expectations. The data from this extension trial suggest that maintaining secukinumab therapy beyond one year can provide sustained benefits and reduce relapse risk. This supports encouraging patients to continue treatment if it is tolerated and effective. However, given the heterogeneity of HS, some patients may do well with treatment pauses, so shared decision-making is crucial.
Britany: Absolutely. It also highlights the importance of regular monitoring, not only of skin lesions but also of patient-reported outcomes such as pain and quality of life. These factors can guide adjustments in therapy intensity or dosing intervals.
Seth: Yes, and considering the safety profile, clinicians should remain vigilant for infections, especially in patients with comorbidities such as diabetes or obesity, which are common in HS populations. Educating patients on infection signs and encouraging timely reporting is essential.
Britany: Another practical consideration is the dosing schedule. The trial compared every two-week and every four-week dosing. While both showed benefits, the every four-week dosing had a slightly longer median time to loss of response. This could influence convenience and adherence.
Seth: Indeed, and cost considerations may also play a role in dosing decisions. Longer dosing intervals might reduce treatment burden and expenses, but individual patient response should guide this choice.
Britany: Looking ahead, integrating biomarkers or imaging techniques to predict which patients will sustain response or relapse could further personalize therapy.
Seth: That would be ideal. Additionally, combining secukinumab with other modalities, such as surgical interventions or lifestyle modifications like weight management and smoking cessation, may optimize outcomes.
Britany: Great points, Seth. Overall, this extension trial adds valuable evidence supporting secukinumab’s role in the long-term management of moderate-to-severe hidradenitis suppurativa, while reminding us of the need for individualized care.
Seth: Exactly. Thank you again for the insightful discussion, Britany.
Britany: Thank you, Seth. And thanks to our listeners for joining us on PACULit. Stay informed and keep striving for excellence in patient care. Until next time.
Seth: Thanks, Britany. Looking forward to our next update. Take care, everyone.