Clindamycin-Benzoyl Peroxide Gel Compared with Clindamycin Lotion for Hidradenitis Suppurativa: A Randomized Controlled Assessor-Blinded Intra-Patient Pilot Study

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent painful inflammatory nodules that can progress to abscesses, tunnels, and scars [1]. Although HS is not primarily an infectious disease, antibiotics are a mainstay in its treatment.

Treatment guidelines recommend topical clindamycin as monotherapy for the treatment of mild to moderate HS [2]. These recommendations are based on two clinical trials which showed favorable results for topical clindamycin compared with placebo and similar results when compared with oral tetracycline [3, 4]. Furthermore, a Hidradenitis Suppurativa Clinical Response (HiSCR) of 52% was shown after 12 weeks of treatment with topical clindamycin by Molinelli et al. [5] in a retrospective study of 72 HS patients.

However, the emergence of bacterial resistance in HS is a serious concern, and high levels of resistance for rifampicin, clindamycin, and tetracyclines have already been demonstrated [6, 7]. This problem urges for a restraint on the long-term use of antibiotics and a need for preparations that are less susceptible to the induction of bacterial resistance. The current treatment guidelines for acne vulgaris already discourage the use of clindamycin as monotherapy due to the risk of bacterial resistance and instead recommend formulations that combine topical antibiotics with other active ingredients, such as benzoyl peroxide and retinoids [8]. It seems logical that topical formulations can also be used in HS; nonetheless, scientific evidence is scarce. Therefore, we sought to explore the feasibility of a randomized, controlled, assessor-blinded, intra-patient pilot trial to investigate the efficacy of clindamycin-benzoyl peroxide gel compared with clindamycin lotion monotherapy for the treatment of mild to moderate HS.

This randomized, controlled, assessor-blinded, intra-patient pilot trial was conducted at the Department of Dermatology of the Erasmus University Medical Center, Rotterdam, The Netherlands, from November 2019 to March 2022. The aim of this trial was to compare the efficacy of clindamycin-benzoyl peroxide gel with clindamycin lotion and to evaluate the feasibility of an intra-patient study design. Contralateral body sites with comparable disease severity were randomized for treatment in blocks of two by an independent researcher in either clindamycin lotion 1% twice daily for 12 weeks or the formulation gel of clindamycin 1% with benzoyl peroxide 5% in a left-right fashion (axillary, inguinal, or gluteal) with a follow-up of 4 weeks to assess sustained efficacy. Visits were conducted by an unblinded physician assistant, and lesion count was performed by an HS investigator, blinded to treatment. Patients were asked to wear white clothes to all visits to prevent de-blinding by possible textile bleaching stains from the benzoyl peroxide. Furthermore, at each visit, the patients were asked for therapy adherence, and the remaining volume and weight of returned flasks were measured at the 12-week visit.

Adult patients with mild to moderate HS, according to the Hidradenitis Suppurativa Physician’s Global Assessment scale (HS‐PGA) [9], were eligible for inclusion. Other inclusion criteria were as follows: two inflammatory lesions in both, contralateral, body sites; a diagnosis of HS for more than 6 months; being able and willing to provide written consent. Exclusion criteria were as follows: a contraindication for clindamycin or benzoyl peroxide, superinfection of HS lesions, other skin condition, presence of uncontrolled disease, pregnant or lactating women, the use of systemic antibiotics 14 days prior to inclusion, and topical antibiotics or resorcinol in the eligible body sites 14 days prior to inclusion.

The primary outcome was the difference in International Hidradenitis Suppurativa Severity Score (IHS4) [10] between the two groups after 12 weeks. Secondary objectives were difference between the two groups in IHS4-55 [11], pain scores (NRS-pain), itch scores (NRS-itch), and satisfaction scores after 12 and 16 weeks. Additionally, within-group differences were tested for IHS4, pain scores, and itch scores between baseline and 12 and 16 weeks. Furthermore, lesional swaps were taken at baseline and after 12 weeks to assess bacterial resistance for clindamycin. Safety and tolerability were checked throughout the whole study.

Baseline characteristics are presented as median (IQR) or n (%). All continuous data were analyzed using the Wilcoxon matched-pair signed-rank test. For categorical variables, differences between groups were assessed using a χ² test or Fisher’s exact test. All comparisons were two sided, and p values ≤0.05 were considered statistically significant. Statistical analyses were performed in SPSS Statistics 28.0 (IBM Corporation, Armonk, NY, USA).

The protocol was reviewed and approved by the Local Medical Ethical Review Board (approval number: MEC-2018-1930), and the study was conducted in accordance with the provisions of the Declaration of Helsinki.

Ten patients were included with a total of twenty body sites. Most patients (80%) were female, median age was 28 [IQR: 22.5–36.3], median BMI was 32.4 [IQR: 27.1–35.6], and 4 patients (40%) were currently smoking. The axillary (40%) and inguinal (40%) body sites were most often treated, followed by the gluteal region (20%). Baseline severity, measured in Hurley staging, resulted in 90% mild patients and 10% moderate patients. However, when using the refined Hurley staging [12], 30% were considered mild (1A), 60% moderate (1B, 2B), and 1 patient was severe (1C) (Table 1).

The IHS4 at baseline was 2 [IQR: 1.8–2] for clindamycin lotion and 2 [IQR: 2–3] for clindamycin-benzoyl peroxide gel. Both therapies lead to an improvement in the IHS4, pain scores, and itch scores, with significant improvements for the IHS4 for both the clindamycin lotion and clindamycin-benzoyl peroxide gel after 16 weeks of treatment, with a median decrease in IHS4 of −1.5 [IQR: −2 to −1], p < 0.05 and −2 [IQR: −2 to −1], p < 0.01, respectively. Furthermore, pain scores were significantly reduced in both groups after 12 weeks, as median pain scores reduced from 7 [IQR: 3.5–7.3] to 2.5 [IQR: 0.8–5.3], p < 0.01 and from 6.5 [IQR: 4.8–8] to 3 [IQR: 0.8–6.5], p < 0.05, for clindamycin lotion and clindamycin-benzoyl peroxide gel, respectively. Although the itch score showed a decline in both groups, no significant differences were found. The dichotomous IHS4 (IHS4-55) showed the same results for both groups, with 50% responders after 12 weeks and 60% responders after 16 weeks. Between the two groups, no statistically significant differences were found. Furthermore, no differences were found for all outcome measures between the two groups.

The majority of patients were satisfied with both therapies (Table 2) and they were well tolerated with only 1 patient who reported mild itching from the treatment in both body sites. A small increase in clindamycin-resistant strains was observed for clindamycin lotion, whereas the clindamycin-resistant strains with clindamycin-benzoyl peroxide gel remained stable (Table 2).

This randomized, controlled, assessor-blinded, intra-patient pilot trial showed similar clinical results for the topical application of clindamycin lotion and clindamycin-benzoyl peroxide gel for patients with mild to moderate HS. Our results, which show a 50% efficacy in IHS4-55 for both groups after 12 weeks, are in line with previous clinical studies investigating the efficacy of topical clindamycin monotherapy in mild to moderate HS [3‒5]. The similar results that were found for clindamycin-benzoyl peroxide gel suggest that this formulation is equivalent to topical clindamycin monotherapy. A shift from clindamycin monotherapy to a combination formulation in mild to moderate patients could contribute to controlling the emergence of bacterial resistance in HS, as is also advised for the treatment of acne vulgaris [8]. This is supported by the increase in clindamycin-resistant strains in the clindamycin monotherapy group compared with a minor decrease in the combination group. However, due to the small sample size, which is a clear limitation of this study, results on efficacy and bacterial resistance should be interpreted with caution and need to be validated in a larger clinical trial.

Furthermore, the feasibility of the study design caused some complications. Although the intra-patient study design reduced the required sample size and could prevent interpatient bias, it complicated patient inclusion as patients rarely presented with similar mild to moderate disease severity in both contralateral body sites. In addition, a minimum required number of four inflammatory nodules in only the two body sites formed an obstacle for the inclusion since the presence of additional inflammatory lesions in other body parts increased overall severity, causing the patient to be no longer eligible for topical therapy alone. Therefore, we would advise against the intra-patient design or to decide for a severity score of the target area.

In this study, a topical formulation was used with clindamycin and benzoyl peroxide. However, it is also possible to combine clindamycin with other compounds, such as retinoids, especially in patients with an acneiform HS phenotype [13]. We would like to encourage the initiation of clinical studies with other topical formulations to expand our topical armamentarium and to reduce antibiotic resistance.

This pilot study showed favorable and similar clinical efficacy results for topical clindamycin-benzoyl peroxide gel and clindamycin lotion. However, we were confronted with the limitations of an intra-patient design for the mild to moderate HS patient population. Larger randomized controlled trials are needed to validate the efficacy of topical combination therapies and to assess their influence on the diversity and resistance patterns in the skin microbiome more extensively.

There is less antibiotic resistance and good clinical efficacy with clindamycin-benzoyl peroxide gel in HS.

This study protocol was reviewed and approved by the Local IRB of the Erasmus University Medical Center, approval MEC-2018-1930. This study was conducted in accordance with the provisions of the Declaration of Helsinki. Written informed consent was obtained from all participants.

The authors have no relevant conflicts of interest to declare.

No funding was received for this clinical trial.

Conceptualization and writing – review and editing: all authors; data curation: Joanne L. Reeves; formal analysis and writing – original draft: Pim Aarts; investigation: Pim Aarts, Joanne L. Reeves, and Christine B. Ardon; methodology: Christine B. Ardon; and supervision: Errol P. Prens and Hessel H. van der Zee.

Data are not publicly available due to ethical reasons. Further inquiries can be directed to the corresponding author.