Biologics and Targeted Small Molecules

1.1 Shared decision-making

When considering biologic or advanced therapy for HS, we recommend engaging in shared decision-making with patients, while taking into account disease severity, comorbidities, and potential drug interactions.

Context :

Initiating biologic or other advanced therapies in HS requires a patient-centered approach. Clinical decisions should be guided not only by objective disease severity but also by comorbidities, potential drug–drug interactions, and the patient’s values and preferences. Shared decision-making is essential to ensure treatment aligns with patient goals and optimizes adherence and outcomes.

1.2 Initiation criteria for biologic or advanced therapy

We recommend considering biologics or advanced therapies in patients with moderate to severe HS who have failed, or have contraindications to, an adequate trial of conventional systemic therapy, which usually consists of 3 months of systemic antibiotic therapy.

Context :

Escalation to biologic or advanced therapy should be considered for patients with moderate to severe HS who have not responded to, or cannot tolerate, conventional systemic treatments such as systemic antibiotics. In the pivotal randomized controlled trials of approved biologic therapies (PIONEER I & II for adalimumab [1], SUNSHINE and SUNRISE for secukinumab [2], and BE HEARD I & II for bimekizumab [3]), failure or contraindication to at least 3 months of systemic antibiotic therapy was an inclusion criterion, ensuring that enrolled patients had previously received standard systemic treatment. These findings reinforce that biologic or advanced therapies are appropriate for patients with persistent, recurrent, or severe disease despite adequate systemic antibiotic management. Early identification of such patients may improve disease control and quality of life while minimizing antibiotic overuse.

1.3 Local approval, access, and implementation considerations

When considering biologics or advanced therapy for HS, we suggest taking into account local practice factors, including regulatory approval, reimbursement, and access.

Context :

Access to biologic and advanced therapies for HS varies widely between regions and healthcare systems. Local regulatory approvals, reimbursement criteria, formulary restrictions, and healthcare infrastructure all influence treatment availability. These practical considerations are important determinants of whether patients can initiate or continue advanced therapies, regardless of clinical eligibility.

1.4 First-line biologic options

When considering biologics or advanced therapy for adult HS patients, we recommend using the approved TNF inhibitor adalimumab and the approved IL-17 inhibitors secukinumab and bimekizumab as first-line therapy.

Context :

Among advanced therapies for HS, TNF-α inhibition (adalimumab) and IL-17 pathway inhibition (secukinumab, bimekizumab) have the most robust evidence and regulatory approvals across multiple jurisdictions. Adalimumab is approved for HS in people aged 12 years and older (adolescents + adults), whereas secukinumab and bimekizumab are approved for adults with moderate-to-severe HS. Pivotal RCTs (PIONEER I & II for adalimumab, SUNSHINE and SUNRISE for secukinumab, BE HEARD I & II for bimekizumab) demonstrated clinically meaningful improvements versus placebo and acceptable safety profiles. No study has directly compared the efficacy of these biologics, and a network meta-analysis found no evidence of superiority of one agent over another. Together, these findings support their placement as first-line biologic options for eligible patients with moderate-to-severe HS.

2.1 First-line anti-TNF therapy

We recommend using adalimumab as the first-line anti-TNF therapy in adolescent and adult patients with moderate-to-severe HS.

Context :

Adalimumab is the only TNF inhibitor approved for HS and has demonstrated efficacy and safety in both adolescent and adult populations. Its approval was based on the pivotal PIONEER I and PIONEER II phase 3 trials, which enrolled patients with moderate-to-severe HS and showed significantly higher HiSCR response rates compared with placebo. These trials established adalimumab as the reference anti-TNF therapy in HS and the standard comparator for subsequent biologic studies.

2.2 Infliximab as a second-line anti-TNF agent after failure or inability to use approved biologics

In patients with moderate-to-severe HS who have failed or cannot use approved biologics for HS, and in whom anti-TNF therapy is desired, we suggest using off-label infliximab as a second-line anti-TNF agent.

Context :

Infliximab has shown clinically meaningful improvement in HS disease activity in a randomized, double-blind, placebo-controlled crossover trial and multiple supportive case series. Responses include reductions in abscess and inflammatory nodule counts and improvements in quality of life. Evidence indicates that higher dosing regimens, typically 7.5 to 10 mg/kg administered every 4-6 weeks, are often required to achieve and maintain optimal clinical response. While infliximab remains off-label for HS, its consistent benefit across studies supports its role as a second-line anti-TNF therapy when adalimumab is ineffective or not tolerated.

2.3 Therapeutic drug monitoring for anti-TNF therapy

In HS patients with suboptimal response to TNF inhibitors, we suggest therapeutic drug monitoring (TDM), when available, to help guide management decisions.

Context :

In HS patients receiving TNF inhibitors who demonstrate a suboptimal or loss of response, TDM may inform next steps in care. HS-specific studies support the clinical utility of assessing serum drug levels and anti-drug antibodies to distinguish pharmacokinetic failure (low levels/antibodies) from mechanistic failure (adequate levels without response). This distinction can guide dose optimization, within-class switching, or transition to another mechanism of action. Given variability in availability and cost, TDM should be individualized and considered a supportive tool rather than mandatory.

2.4 Off-label dose escalation of anti-TNF therapy

In HS patients with suboptimal response to TNF inhibitors, we suggest considering dose escalation (e.g., increased frequency or higher dose), based on clinical judgment and patient-specific factors.

Context :

In HS, some patients treated with TNF inhibitors may not achieve or maintain adequate disease control at standard doses. Evidence supports the role of adalimumab dose escalation (e.g., increasing to 80 mg weekly) in improving outcomes. Therapeutic drug monitoring may further guide this approach in identifying patients who are likely to benefit. For infliximab, intensification strategies such as increasing to 10 mg/kg every 8 weeks or shortening the interval to every 4 weeks have been shown to improve control in patients with inadequate response.

2.5 Certolizumab as an alternative anti-TNF option after approved biologics

In patients with moderate-to-severe HS who have failed or are unable to use approved biologics for HS, and in whom anti-TNF therapy is desired, we suggest considering off-label certolizumab pegol, particularly in pregnancy.

Context :

The evidence for certolizumab pegol in HS consists of small case series, retrospective cohorts, and individual case reports. These studies indicate that certolizumab may reduce inflammatory lesion counts and improve symptoms in a subset of patients with refractory HS. Given its minimal placental transfer and accumulated clinical experience supporting its safety in pregnancy, certolizumab may be particularly appropriate for pregnant patients or those planning pregnancy. Use should be individualized, taking into account prior biologic failures, comorbidities, and patient preference.

2.6 Etanercept should not be used for HS

In patients with HS who require advanced therapies, we recommend against the use of etanercept.

Context :

Etanercept has been studied in HS in limited prospective trials and case reports, with no evidence of significant clinical benefit. In a small randomized controlled trial (n≈20), etanercept 50 mg twice weekly for 12 weeks did not achieve improvement in disease severity, pain, or quality of life compared to placebo. Other small uncontrolled studies similarly reported minimal or no sustained improvement. In contrast, monoclonal anti-TNF antibodies such as adalimumab and infliximab demonstrate clear efficacy in HS. Based on this consistent lack of benefit, etanercept should not be used for HS management.

2.7 Perioperative use of biologic therapy in HS surgery

We suggest continuing biologic therapy during the perioperative period for HS surgery, with the best available evidence supporting continuation of adalimumab.

Context :

Perioperative management of biologics in HS should balance the risk of postoperative complications with the risk of disease flare if treatment is interrupted. The SHARPS randomized controlled trial demonstrated that continuing adalimumab through the pre-, intra-, and postoperative periods of wide-local excision did not increase surgical complications and was associated with improved global disease control and patient outcomes. Additional real-world evidence supports the safety and practicality of maintaining biologic therapy during HS surgery. Based on current evidence, adalimumab may be continued without interruption in the perioperative period, while data for other biologics remain limited. Clinical judgment should guide decisions for newer agents, considering wound extent, infection risk, and disease activity.

3.1 Secukinumab and bimekizumab as first-line IL-17i therapies

In adult patients with moderate-to-severe HS, we recommend using secukinumab or bimekizumab as the first-line IL-17i therapy.

Context :

Pivotal RCTs (SUNSHINE and SUNRISE for secukinumab, BE HEARD I & II for bimekizumab) demonstrated clinically meaningful improvements versus placebo and acceptable safety profiles.

3.2 Off-label IL-17 inhibitors after failure of approved biologics

In patients with moderate-to-severe HS who have failed or cannot use approved biologics for HS, and in whom IL-17 inhibitor therapy is desired, we suggest using off-label IL-17 inhibitors.

Context :

IL-17 inhibitors play an important role in HS, with secukinumab and bimekizumab approved for HS in many jurisdictions. Off-label IL-17 inhibitors may offer benefit in selected patients with refractory HS after failure of approved IL-17 inhibitors or other advanced therapies. Evidence is limited to uncontrolled studies and small case series. Brodalumab, an IL-17 receptor A antagonist, has the most supportive data among off-label IL-17 inhibitors, with retrospective studies demonstrating improvements in inflammatory lesion burden and patient-reported outcomes in patients who had previously failed multiple biologic therapies. A broader review of off-label biologic use in HS reinforces the potential role of IL-17 pathway blockade as a salvage strategy in highly refractory disease. Given the limited evidence, treatment should be individualized, considering prior biologic history, comorbidities, and safety considerations.

4.1 Ustekinumab as an alternative treatment for selected patients with HS

In patients with moderate-to-severe HS who have failed or are unable to use approved biologics for HS, and in whom IL-12/23 blockade is desired, we suggest that off-label ustekinumab may provide benefit particularly in patients with concurrent inflammatory bowel disease.

Context :

The evidence for ustekinumab comes from 1 prospective single arm trial of 17 patients and multiple case series of a total of 71 patients. In the prospective trial, 47% of patients achieved HiSCR at 40 weeks. Across the case series, there was a large range of response rates and doses of ustekinumab, with different assessments of efficacy reported at different time points, with an overall poor quality of evidence. Ustekinumab is also approved for treatment of Crohn’s and ulcerative colitis in many jurisdictions. Patients with inflammatory bowel disease were included in many case series of patients with HS treated with ustekinumab, but specific success rates in these patients is not extractable. There are also reports of patients with HS and TNF-induced psoriasis, with or without inflammatory bowel disease, who achieve response with ustekinumab.

4.2 IL-23 inhibitors as a 2nd line alternative treatment in the IL12/23 pathways for selected patients with HS

We suggest reserving off-label use of IL-23 inhibitors for patients with HS who have failed to respond to other advanced therapies, particularly when comorbid conditions that may benefit from IL-23 blockade are present.

Context :

There are 3 IL-23 inhibitors available for non-HS indications which have been used in patients with HS (tildrakizumab, guselkumab and risankizumab).

The evidence for tildrakizumab comes from 2 case series and 2 case reports describing 18 patients. Overall, these case reports and series demonstrated a reduction in the abscess and inflammatory nodule after beginning tildrakizumab. Most adverse effects were minor and did not result in discontinuation. The average pretreatment nodule count was 13.75, and last recorded value was 6.31 (16/17 reported values), representing a delta of −7.44.

For guselkumab, 3 studies (1 RCT, 1 retrospective cohort, and 1 case report) reported on 135 patients. In a phase 2 RCT, guselkumab SC (n=59) and IV (n=60) resulted in numerically but not statistically higher HiSCR versus placebo at Week 16 (50.8%, 45.0%, 38.7%). In a retrospective cohort study, when guselkumab was used for a minimum of 90 days (N=15), it was associated with a median drug survival of 18.9 weeks, and 75% discontinued because of lack of efficacy. Finally, In a case report , a patient who failed a TNF-inhibitor was treated with guselkumab and achieved HiSCR at week 16 and week 52.

For rizankizumab, a phase 2 multicenter placebo-controlled RCT evaluated 2 doses (n=80+81) compared to placebo (n=82). Risankizumab was associated with a numerically but not statistically significant higher HiSCR at 16 weeks vs placebo (46.8% vs 43.4% vs 41.5%). Reductions in AN count, abscesses, draining fistulas, and inflammatory nodules were also similar across treatment groups.

5.1 Anakinra as an IL-1 inhibitor option, after use of approved biologics

In patients with moderate-to-severe HS who have failed or cannot use approved biologics for HS, and in whom IL-1 inhibitor therapy is desired, we suggest considering off-label anakinra, particularly in patients with auto-inflammatory features.

Context :

This recommendation is primarily supported by a single, double-blind, randomized, placebo-controlled trial that provides moderate-certainty evidence of a net benefit. The trial demonstrated a statistically significant and clinically meaningful improvement, with 78% of patients receiving anakinra achieving a Hidradenitis Suppurativa Clinical Response (HiSCR) at 12 weeks compared to 30% of those receiving placebo. Despite the robustness of the study design, which confers a high initial quality of evidence, the certainty was downgraded to moderate due to serious imprecision stemming from the very small sample size (N=20).

Case reports and small observational studies document the use of anakinra in patients with PASH (pyoderma gangrenosum, acne, suppurative hidradenitis) and PAPASH (pyogenic arthritis, pyoderma gangrenosum, acne, suppurative hidradenitis) syndromes. These syndromes are rare autoinflammatory disorders linked to IL-1 pathway dysregulation.

6.1 Upadacitinib as an alternative treatment for selected patients with HS

We suggest that off-label upadacitinib may provide benefit in adults with moderate-to-severe HS who have a contraindication to or have failed approved therapies for HS or have comorbidities for which upadacitinib is approved.

Context :

The evidence for upadacitinib comes from 1 small placebo controlled RCT (N=47), a retrospective cohort study (N=20) and 2 case reports. In the RCT, 38.4% of patients achieved HiSCR50 at week 12 compared to 25% in the placebo arm. In the cohort study, 100% achieved HiSCR50 at week 12, which was maintained at week 52. The 2 patients in the case reports had concurrent ulcerative colitis for which upadacitinib is approved. Both responded well, with one also initially receiving concurrent adalimumab.