FormalPara Key Summary Points

Why carry out this study?

For patients with hidradenitis suppurativa (HS), biologics are often reserved for severe disease after irreversible damage has occurred.

There is a need to understand how consistent treatment (12 weeks or more) with biologics affects the requirement for medical and surgical interventions.

What was learned from the study?

Using data from UNITE, a 4-year, global HS disease registry, this study showed that fewer patients required procedural interventions (steroid injections, drainage of boils, surgery), emergency department visits, hospital admissions, and visits to healthcare providers for HS following consistent treatment with biologics.

In UNITE, a reduced need for certain procedures and healthcare requirements was observed in patients initiating consistent treatment with biologics, suggesting that biologics should be started earlier. Additional research is warranted to confirm these findings.

Introduction

Hidradenitis suppurativa (HS) is a painful, chronic, inflammatory skin disease characterized by recurrent nodules, abscesses, cutaneous tunnels, and scarring [1]. HS carries a high comorbidity burden and has debilitating effects on patient quality of life and work productivity [2, 3]. The estimated prevalence of HS is 0.1–1% of the general population, and HS disproportionately affects women versus men and black versus white individuals [1, 4, 5].

Management of HS often requires a combined medical and surgical approach. Generally, topical or systemic antibiotics are first-line therapies, although evidence for efficacy is limited [6,7,8]. Biologics (e.g., tumor necrosis factor [TNF] inhibitors) are often reserved for patients with severe disease who have experienced irreversible tissue damage [6, 8]. Some biologics not approved for the treatment of HS may also be safe and effective [9]. Intralesional corticosteroid injections and incision and drainage (I&D) are used to manage acutely painful lesions but are associated with high recurrence rates [6, 8]. Surgical procedures (e.g., deroofing, excision) are often required to remove tunnels and scar tissue; however, extensive surgery can be associated with postoperative morbidity (infection, bleeding, and contracture) [6, 8, 10]. Although biologics have been shown to be safe and effective alone and in combination with surgery [11,12,13,14], a recent cross-sectional analysis revealed low utilization of TNF inhibitors for the treatment of HS [15]. Furthermore, information on how consistent treatment with biologics affects medical and procedural interventions is limited.

UNITE is a 4-year, global, prospective, observational, HS disease registry documenting the natural history, diagnostic and treatment patterns, and clinical outcomes of patients with HS [16]. A recent analysis of UNITE demonstrated that HS is a highly progressive disease; the majority of the 574 enrolled patients experienced lesion or scar spread or Hurley stage progression over a 4-year period [17]. Disease progression occurred most frequently in patients with more severe, long-standing disease, highlighting the importance of early management to minimize the debilitating consequences of disease progression [17].

The objective of this analysis of the UNITE registry was to evaluate the association between consistent biologic use and the need for procedural interventions, systemic medications, and healthcare utilization.

Methods

UNITE enrolled patients (aged 12 years or more) with active HS (defined by the presence of inflammatory HS lesions) and no previous or current participation in an adalimumab clinical study or registry [16]. Patients were enrolled between October 2013 and December 2015 from 73 sites across 12 countries in North America, Europe, and Australia and received treatment per routine clinical practice [16]. Patients were evaluated every 6 months for up to 48 months (data cutoff December 2019).

This analysis included patients who reported newly initiated biologic use for HS with 12 weeks or more of use (i.e., consistent use) in the past 6 months. All patients or their legal guardians signed an informed consent form that was approved by an institutional review board or ethics committee according to local law. A list of all study sites and information on ethics committees who approved this study is provided in Supplemental Table 1.

Endpoints

Data were compared between three 6-month periods: the period before initiation of consistent use of biologics (period 1), period during which the consistent use of biologics was initiated (period 2), and period after the initiation of consistent biologics use (period 3; Fig. 1).

Fig. 1
figure 1

UNITE visits and assessment periods. The proportions of patients requiring procedures, systemic medications, and healthcare utilization for hidradenitis suppurativa were assessed during three 6-month periods between UNITE visits: period 1, before initiation of consistent biologics use; period 2, during initiation of consistent biologics use; and period 3, after initiation of consistent biologics use

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The assessed endpoints included the proportions of patients requiring surgical/procedural interventions (including intralesional corticosteroid injections, I&D by physician, I&D by patient, excision, deroofing, laser therapy, and photodynamic therapy), proportions of patients with systemic medication use (antibiotics, immunosuppressants, pain medications, hormonal agents, and retinoids), and the proportions of patients requiring any hospital bed use, hospital admission, emergency department (ED) visit, or visits to dermatologists, any healthcare providers (HCPs), primary care physicians (PCPs), or surgeons for HS.

Statistical Analysis

All baseline demographics and disease characteristics were summarized by descriptive statistics. Mean (SD) was reported for continuous variables and number and proportion for categorical variables.

Results

Of the 594 patients with HS enrolled in UNITE who provided baseline data [16], postbaseline data were available for 574 patients, including 62 adolescents. Of these, 57 reported 63 instances of initiation of consistent biologic use. Their mean age was 40 years, 58% were female, and 53% and 47% had Hurley stage II and III disease, respectively (Table 1). Biologic initiations were adalimumab (51 [81%]), infliximab (10 [16%]), and ustekinumab (2 [3%]).

Table 1 Baseline patienta characteristics and demographics
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Fewer patients required surgical/procedural interventions during periods 2 and 3 versus period 1, including for intralesional corticosteroid injections, I&D by physician, I&D by patient, deroofing, and excision (Fig. 2). This trend was more pronounced for procedures tied to acute disease flares, including intralesional corticosteroids and I&D procedures, compared with those more likely to be planned for chronic disease, such as deroofing and excision. No difference was observed for photodynamic therapy between the periods, whereas laser treatments increased from period 1 (none) to periods 2 and 3 (5% each).

Fig. 2
figure 2

Proportions of patients requiring procedural/surgical interventions, systemic medications, and healthcare utilization before, during, and after initiation of consistent use of biologics. Data are based on 63 initiations of biologics. ED emergency department, HCP healthcare provider, IMM immunosuppressants, PCP primary care physician

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Similarly, the number of any hospital admissions, ED visits, or any HCP, dermatologist, or PCP visits for HS was lower during period 2 versus period 1, with continued declines or maintenance noted during period 3 (Fig. 2). In contrast, hospital bed use or surgeon visits increased from period 1 to period 3.

The use of systemic antibiotics and immunosuppressants declined during periods 2 and 3 compared with period 1 (Fig. 2). However, the use of pain medications and hormonal agents increased from period 1 to period 3.

Overall, the results were generally similar when assessing only adalimumab initiations (Fig. 3).

Fig. 3
figure 3

Proportions of patients requiring procedural/surgical interventions, systemic medications, and healthcare utilization before, during, and after initiation of consistent use of adalimumab. Data are based on 51 initiations of adalimumab. ED emergency department, HCP healthcare provider, IMM immunosuppressants, PCP primary care physician

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Discussion

In UNITE, after initiation of biologics for 12 weeks or more in patients with active HS, fewer acute procedures, systemic medications, hospitalizations, ED visits, or HCP visits were required during the 6 months in which the biologic was initiated and the 6 months following initiation compared with the 6 months before initiation. Notably, ED visits halved from period 1 to period 2 and 3. An analysis including only adalimumab initiations yielded similar results. These findings suggest that consistent biologic use reduces the need for acute episodic interventions and invasive surgeries, supporting the importance of early initiation.

Although HS is a chronic disease with a remitting-relapsing course and frequent painful flares [1], for many patients it is managed reactively, with acute procedural/surgical interventions without medications that address the underlying disease. Poorly controlled disease results in accumulation of tissue damage, often requiring costly and invasive procedures. As demonstrated previously in UNITE, the majority of patients experienced disease progression over 4 years despite routine clinical care [17].

Our findings also suggest that sustained biologic treatment helps address the underlying disease process and therefore reduces the need for acute interventions. Furthermore, biologics may be useful in reducing disease progression when used appropriately as part of a comprehensive management plan [11,12,13]. Currently, only one biologic, the TNFα inhibitor adalimumab, is approved by the US Food and Drug Administration and European Medicines Agency for the treatment of moderate to severe HS. Several other biologics have shown beneficial effects in exploratory studies of limited duration and small sample sizes [7]. Although most concomitant medication use decreased during the 6-month period of biologic initiation and following the initiation, the use of pain and hormonal medications increased from period 1 to period 3. The reasons for the increases are unknown, but they may be related to use of these medications as an adjunctive therapy in combination with biologics and, in the case of pain medications, for the treatment of unpredictable pain during HS flares, which is a common feature of the disease. Hospital bed use and surgeon visits increased from period 1 to period 3; however, these visits could reflect preplanned surgeries for long-standing disease or suggest the need of surgery in patients with advanced end-stage disease for whom the use of biologics might have limited success.

This analysis included patients who were treated in routine clinical practice with no specific restrictions. Because of this, concomitant therapies could have confounded the results; however, this patient population also gives a better representation of real-world clinical practice. Main limitations of this analysis included a lack of statistical testing and comparisons between the groups. Other limitations included small sample size, possible biases in patient selection, recall of information, inconsistent reporting, and measurement errors. Additionally, if a patient discontinued a biologic after 12 weeks of use, they were still included in the analysis because consistent use of biologics was defined as 12 weeks or more of use. Furthermore, patients who stay in registries may be self-selecting for favorable effectiveness. Additional studies are needed to confirm the findings of our analysis.

The main strengths of this study included that UNITE was the first and, at the time of completion, largest global real-world HS registry, making the results generalizable to clinical practice. In addition, patients were compared before and after biologic initiation, controlling for confounding that could result from comparing separate cohorts with individual differences.

Conclusions

Overall, these results demonstrate that initiation and consistent use of biologics could result in fewer procedures, reduced systemic medication use, and reduced utilization of healthcare resources compared with before initiation. Early initiation of biologics may be beneficial to improve the disease trajectory in patients with moderate to severe HS.