Real-World Data Highlight Adalimumab Biosimilar Options for Hidradenitis Suppurativa

People living with hidradenitis suppurativa (HS) often rely on long-term biologic therapy to manage painful and recurring inflammatory symptoms, but access to treatment can be shaped by cost, formulary design, and pharmacy-level decisions.¹ As biosimilars increasingly become the default option in many health systems, new real-world data provide important insight into how these products may perform in a chronic condition where treatment stability is a core goal.

New research reveals that switching from originator to biosimilar adalimumab for hidradenitis suppurativa may lead to reduced treatment effectiveness and stability. | Image credit: Orawan - stock.adobe.com

The multicenter analysis, published in JAAD International, evaluated clinical outcomes among adults with HS who initiated either originator or biosimilar adalimumab between April 2021 and December 2024. It also examined outcomes for individuals who initially responded to originator adalimumab but were later transitioned to a biosimilar due to nonmedical formulary changes—an increasingly common scenario as payers shift toward lower-cost products.

HS is a chronic, painful inflammatory skin disease characterized by nodules, abscesses, and tunnels that often require durable immunomodulation. While biosimilars are designed to replicate the safety and efficacy of the reference biologic, small manufacturing variations can influence immunogenicity or drug persistence, prompting ongoing debate about whether the 2 product types perform equivalently in certain conditions. Because adalimumab remains 1 of the few available biologic options for HS, questions about switching and long-term control are particularly relevant for both clinicians and managed care organizations.

Study Cohorts and Clinical Measures

The analysis included 313 treatment-naïve individuals with dermatologist-confirmed HS. Those who initiated the originator product (n = 186) and those who started a biosimilar (n = 127) demonstrated similar baseline demographics, including median age (31 vs 30 years), sex distribution, body mass index (BMI), smoking status, and Hurley stage. All individuals followed the same dosing regimen recommended by major regulatory agencies.

A second matched cohort assessed the effects of nonmedical switching. Seventy-one individuals who achieved clinical response (HiSCR-50) on originator adalimumab at week 16 and were subsequently switched to a biosimilar were compared with 71 matched individuals who remained on the originator product. Matching ensured comparability across age, sex, BMI, smoking status, and Hurley stage.

Clinical outcomes were measured using established HS tools: HiSCR-50, HiSCR-75, and the International Hidradenitis Suppurativa Severity Scoring System (IHS4-55). Time-to-event analysis evaluated loss of response, defined as loss of HiSCR-50.

Differences in Response and Durability Emerge Over Time

Early outcomes at week 16 showed similar proportions achieving HiSCR-50 across treatment-naïve groups (P = .27), but the originator group demonstrated a significantly higher rate of HiSCR-75 (33% vs 30%; P = .008). By week 52, differences across all measures widened, with originator-treated individuals more likely to achieve:

• HiSCR-50: 51% vs 24% (P = .0001)
• HiSCR-75: 24% vs 14% (P = .0076)
• IHS4-55: 45% vs 22% (P = .0001)

Durability of response followed a similar pattern. Median time to loss of HiSCR-50 was 100 weeks for originator-treated individuals compared with 52 weeks for biosimilar-treated individuals, with a hazard ratio of 2.73 for loss of response among biosimilar users (P < .0001). In adjusted regression analysis, biosimilar initiation was associated with a 77% increased odds of losing clinical response (odds ratio = 1.767; P = .03).

For those who switched after early response, the median time to loss of HiSCR-50 was 50 weeks compared with 87 weeks among individuals who remained on the originator (hazard ratio, 2.42; P = .0003). Switching was associated with nearly a threefold increase in the odds of losing clinical response (odds ratio = 2.807; P = .0024) after adjustment for body mass index and Hurley stage.

Context and Limitations

Investigators noted that the retrospective design and variability in biosimilar formulations across sites were key limitations. Despite this, the sample size exceeded that of prior HS-focused biosimilar assessments, and matching in the switching cohort strengthened the interpretability of those comparisons.

The findings aligned with earlier reports suggesting that some individuals with HS may experience loss of response or reduced tolerability following nonmedical switching. Previous reports have also documented injection-site reactions and reduced effectiveness after transitions from the originator product, though evidence has varied depending on condition and population.

Potential Impact of the Nocebo Effect

Beyond pharmacologic and immunogenic factors, the nocebo effect may play a meaningful role in real-world outcomes when individuals with HS are switched from originator biologics to biosimilars. The nocebo effect occurs when negative expectations or beliefs about a treatment contribute to perceived or actual worsening of symptoms, reduced adherence, or discontinuation, even when the therapy is pharmacologically equivalent. In chronic conditions like HS, where treatment stability is essential for maintaining disease control and preventing painful flares, the psychological impact of nonmedical switching may amplify the risk of symptom recurrence or perceived loss of efficacy.

Evidence from the study highlights that individuals who were stable on originator adalimumab but transitioned to a biosimilar experienced a median time to loss of clinical response that was nearly halved compared with those who remained on the originator. While manufacturing differences and immunogenicity could partially explain these findings, prior research in other inflammatory diseases suggests that patient expectations and concerns about efficacy and tolerability can contribute significantly to reduced response following nonmedical switching. Injection-site reactions, fatigue, or other subjective experiences may be interpreted as treatment failure, leading to decreased adherence or premature discontinuation.

Acknowledging the potential role of the nocebo effect has important implications for clinical practice and managed care strategies. Clinicians and pharmacy teams can mitigate its impact through proactive education, transparent communication about biosimilar equivalence, and shared decision-making that addresses patient concerns. Ensuring that patients understand the rationale for switching, the regulatory rigor behind biosimilar approval, and strategies for monitoring disease control may help preserve confidence in therapy and maintain long-term outcomes.

In the context of expanding biosimilar adoption for HS, integrating strategies to minimize the nocebo effect alongside careful monitoring of clinical response will be key to optimizing both patient experience and therapeutic durability.

Implications for Clinical and Managed Care Decision-Making

As biosimilar use expands, formulary changes often occur independently of clinical concerns, placing individuals with stable disease at potential risk of unintended therapeutic disruption. For a chronic inflammatory condition marked by recurrent flares and limited biologic alternatives, treatment consistency remains a meaningful consideration for long-term disease control.

The authors emphasized the need for HS-specific equivalence studies, as biosimilar approvals for adalimumab do not require clinical trials in HS and instead rely on extrapolation from psoriasis and other conditions. As biosimilar markets grow to include agents targeting interleukin-12/23 and interleukin-17 pathways, understanding how these products perform specifically in HS will be essential for optimizing care and informing future formulary policy.

Reference

1. Aghajani M, Pham J, Sholji T, Burrell K, Kok C, Frew JW. Originator versus biosimilar adalimumab in hidradenitis suppurativa: A multicenter real-world analysis of clinical response, maintenance of response, and switching. JAAD Int. 2025:24:9-15. doi:10.1016/j.jdin.2025.05.023