Abstract
Introduction
Hidradenitis suppurativa (HS) is a chronic inflammatory follicular disorder commonly managed with antibiotics, despite increasing antimicrobial resistance (AMR).
Methods
This single-center retrospective study evaluated the efficacy and safety of 40 mg modified-release doxycycline (MR-DC) in 66 adults with HS treated for 28 days.
Results
Response to treatment was assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the International Hidradenitis Suppurativa Severity Score System (IHS4) scales. Specifically, at 12 weeks, HiSCR50 and IHS4-55 responses were achieved in 75.8% and 87.9% of patients, respectively. Relapse occurred in 33% at 6 months. Lower baseline IHS4, shorter disease duration, lower BMI, higher total inflammatory nodule and abscess count, absence of involvement of the pubis and genital area, and use of concomitant treatment were associated with better outcomes; only shorter disease duration remained significant on multivariate analysis (P < 0.022). Compared to results from other studies using standard regimens of regular-release doxycycline (RR-DC), MR-DC appears to have similar efficacy and more favorable safety profile.
Conclusions
Low-dose MR-DC may be an effective short-term treatment or adjunctive therapeutic option for HS flares, with a reduced risk of AMR and adverse events.
Keywords: Antimicrobial resistance, Doxycycline, Hidradenitis suppurativa, Modified-release doxycycline treatment outcomes
Key Summary Points
| Why carry out this study? |
| HS is a chronic inflammatory skin disease that causes painful nodules, abscesses, and tunnels, substantially impairing patients' quality of life. Although HS is not primarily an infectious disease, antibiotics are commonly used for its management. |
| Standard-dose doxycycline may contribute to AMR and adverse events. Low-dose MR-DC retains anti-inflammatory effects while remaining below the antimicrobial threshold, but evidence supporting its use in HS remains limited. |
| The aim of this study was to evaluate whether low-dose (40 mg) MR-DC is an effective and safe treatment for HS in routine clinical practice. |
| What was learned from the study? |
| Low-dose MR-DC may represent a safe and effective antibiotic resistance-sparing option for the short-term management of HS flares, particularly in patients with a shorter disease duration. |
| These real-world findings provide a rationale for larger prospective studies to confirm efficacy, establish the optimal treatment duration, and identify the patients most likely to benefit from this approach. |
Introduction
Hidradenitis suppurativa (HS) is a chronic skin condition of the hair follicle characterized by nodules, abscesses, tunnels, suppuration, scarring, and pain significantly affecting patients’ quality of life [1]. Although not being primarily an infectious disease, European guidelines recommend antibiotics for its management, including topical clindamycin, oral tetracyclines, and the combination of clindamycin and rifampicin [1, 2].
Doxycycline is a wide-spectrum tetracycline with favorable safety profile that exhibits immunomodulatory and anti-inflammatory properties by influencing specific molecules and biological pathways significant in the pathogenesis of HS (Fig. 1) [2, 3]. However, standard antibiotic doses (100 mg every 12 h) can induce microflora alterations, diarrhea, increase antimicrobial resistance (AMR), and heighten susceptibility to severe infections [3]. Moreover, high resistance to tetracyclines (84.7%) has already been identified in cultures from HS lesions [4].
Fig. 1.
Doxycycline inhibits matrix metalloproteinases (MMP) 2, 3, 8, 9, and 13 and the monocyte chemotactic protein, reducing interleukin-8 (IL-8) and impacting leukocyte chemotaxis and inflammatory cytokines. Doxycycline also hinders the nuclear factor kappa B (NF-κB) pathway and tumor necrosis factor (TNF)-converting enzyme, decreasing the levels of TNF, IL-1, IL-6, and IL-8. It prevents the activation of protease-activated receptor 2, which would stimulate the synthesis of TNF and IL-1β. Additionally, it inhibits phospholipase A2 (a significant molecule in inflammatory processes), protein kinase C (crucial in granuloma formation), and nitric oxide synthase (promoting molecular degradation). K keratinocytes, B B lymphocytes, M1 macrophage, TLR4 Toll-like receptor 4, STAT-1 signal transducer and activator of transcription 1, VEGF vascular endothelial growth factor, CD4 T CD4 T lymphocytes. Created in BioRender.(2026) https://BioRender.com/ralkw6u
Increasing AMR represents a global public health threat arising from the improper use of antibiotics, with approximately 50% of outpatient prescriptions being inappropriate [5]. Although antibiotic prescriptions by dermatologists have recently decreased by 36.6%, there is still room for improvement [5].
The 40 mg modified release doxycycline (MR-DC) dosage (approved by the European Medicines Agency for the treatment of papulopustular rosacea) preserves anti-inflammatory properties below the antimicrobial threshold [6], showing comparable efficacy and superior safety compared to the 100 mg RR-DC for the management of moderate to severe inflammatory acne [7].
Given the limited evidence available on the use of MR-DC in routine clinical practice for the treatment not only of inflammatory dermatological diseases but specifically in HS, the aim of this study was to evaluate the effectiveness and safety of 40 mg MR-DC in patients with HS under real-world conditions.
Methods
We conducted a single-center retrospective observational study of adult patients with HS followed in an HS monographic unit of a tertiary hospital in Barcelona. The main objective was to evaluate the efficacy and safety of 40 mg MR-DC for 28 days for the management of HS under real-life conditions. The primary efficacy endpoint was achievement of HiSCR50 at week 12. Secondary endpoints included achievement of IHS4-55 and the reporting of treatment-associated adverse events at week 12, as assessed during routine clinical practice.
No formal sample size calculation was performed; all eligible patients considered candidates for doxycycline according to European guidelines and treated with MR-DC in the HS clinic during the study period were included. Patients who had undergone any modification in their HS treatment within the previous 6 months were excluded.
This study was approved by the Hospital Ethics Committee (protocol code IIBSP-DOX-2024-9), which waived the requirement for informed consent to conduct the study because of the retrospective nature of data collection from routine practice records. This investigation complied with Good Clinical Practice standards and the International Council for Harmonization directives, as well as the ethical principles outlined in the Declaration of Helsinki. All data were anonymized prior to analysis.
Statistical analyses were conducted with using SPSS v26.0; p < 0.05 was considered significant.
Results
A total of 66 adult candidates to initiate treatment with doxycycline (according to European guidelines) received 40 mg MR-DC for 28 days, between April 2022 and June 2023. The participants’ demographics, baseline clinical characteristics, and concomitant treatments are detailed in Table 1.
Table 1.
Characteristics of patients with hidradenitis suppurativa treated with 40 mg MR-DC daily for 4 weeks
| Total patients, n (%) | 66 (100) |
| Women | 34 (52) |
| Men | 32 (48) |
| Days of follow-up, mean (SD) | 184.61 (81.98) |
| Age, mean (SD) | 35.86 (12.26) |
| Age at onset, mean (SD) | 21.68 (10.56) |
| Disease duration (years), mean (SD) | 15.5 (11.81) |
| BMI, mean (SD) | 27.1 (5.50) |
| Overweight (BMI 25–30), n (%) | 25 (37.88) |
| Obesity (BMI > 30), n (%) | 13 (19.69) |
| Smoking, n (%) | 41 (62) |
| Affected areas, n (%) | |
| Armpit | 38 (57.58) |
| Groin | 49 (74.24) |
| Pubis/scrotum | 36 (54.55) |
| Gluteal | 37 (56.06) |
| Submammary/breast | 15 (22.73) |
| Other locations | 6 (9.09) |
| Baseline lesion count, mean (SD) | |
| Inflammatory nodules | 6.14 (5.2) |
| Abscesses | 1.80 (2.72) |
| N + A | 7.97 (6.46) |
| Draining tunnels | 1.49 (2.24) |
| Baseline Hurley Severity Index, n (%) | |
| Hurley 1 | 14 (21.21) |
| Hurley 2 | 45 (68.18) |
| Hurley 3 | 7 (10.61) |
| Baseline IHS4, mean (SD) | 15.16 (12.23) |
| Adherence to treatment, n (%) | |
| Total | 51 (77.27) |
| Partial | 8 (12.12) |
| Concomitant therapies,a n (%) | 28 (42) |
| Biological treatment | 6 (9.09) |
| High-potency topical CS | 19 (28.79) |
| CS local infiltrations | 3 (4.55) |
| Topical antibiotics | 5 (8) |
| Metformin | 3 (4.55) |
| HiSCR50 week 12, n (%) | 50 (75.76) |
| IHS4-55 week 12, n (%) | 58 (87.88) |
| Adverse events, n (%) | 3 (4.55) |
SD standard deviation, BMI body mass index, N + A inflammatory nodules and abscesses, CS corticosteroids, MR-DC modified release doxycycline, HiSCR Hidradenitis Suppurativa Clinical Response, IHS4 International Hidradenitis Suppurativa Severity Score System
aConcurrent therapies, for at least 6 months at stable doses
HiSCR50 was achieved in 50 (75.8%) patients and IHS4-55 in 58 (87.9%), at 12 weeks of follow-up. In total, 28 (42%) patients utilized adjunctive therapies at stable doses for at least 6 months. Twenty-two patients (33%) reported relapse of preexisting or new inflammatory lesions at 6 months of treatment completion.
A statistically significant probability of reaching HiSCR50 was associated with lower baseline IHS4 (P = 0.007, OR 1.3173, 95% CI 1.077–1.611), shorter disease duration (P = 0.035, OR 0.902, 95% CI 0.820–0.993), lower body mass index (P = 0.002, OR 0.852 95% CI 0.719–0.911), higher total inflammatory nodule (mean 0.73 vs. 7.76, P < 0.001) and abscess count (mean 0.40 vs. 2.22, P < 0.001), absence of involvement of the pubis and genital area (P = 0.032), and use of concomitant treatment (P = 0.041), as shown in Table 2. Nonetheless, no statistically significant likelihood was found with the basal draining tunnel count (P = 0.92) or other affected areas (P > 0.05). On multivariate analysis, only shorter disease duration remained independently associated with achieving HiSCR50 (OR 0.885, 95% CI 0.798–0.983; P = 0.022).
Table 2.
Factors associated with achieving HiSCR50
| Variable evaluated | Univariate analysis (unadjusted OR [95% CI]) | Univariate analysis (P value) | Multivariate analysis (adjusted OR [95% CI]) | Multivariate P value |
|---|---|---|---|---|
| Disease duration | 0.902 (0.820–0.993) | 0.035 | 0.885 (0.798–0.983) | 0.022 |
| BMI | 0.852 (0.719–0.911) | 0.002 | 0.849 (0.690–1.044) | 0.120 |
| Baseline IHS4 | 1.317 (1.077–1.611) | 0.007 | 1.208 (0.988–1.476) | 0.065 |
| Concomitant treatment | 1.102 (1.088–1.116) | 0.041 | Not significant | 0.846 |
OR odds ratio, BMI body mass index, IHS4 International Hidradenitis Suppurativa Severity Score System
Treatment was well tolerated, with only three adverse events (AE) reported including recurrent mild upper respiratory tract viral infections in a patient with a history of prior recurrent infections, and two with gastrointestinal discomfort, although none required drug withdrawal.
Discussion
In the only single-center and open-label study comparing 40 mg MR-DC once daily versus 100 mg of RR-DC twice daily for 12 weeks, conducted in 49 patients with HS, MR-DC showed a significant reduction of IHS4 and DLQI, fewer AEs, and comparable effectiveness to the higher doses, with 16 of 25 (64%) patients receiving 40 mg MR-DC achieving an HiSCR50 [6]. Previous reports and case series with RR-DC observed that between 40% and 60% of patients achieved HiSCR50 after 12 weeks of treatment, although around 16% presented gastrointestinal EA and 10.7% of patients discontinued treatment [8].
Clinical response was assessed at 12 weeks to evaluate not only the immediate effect of treatment but also the persistence of its anti-inflammatory benefit after discontinuation, which is clinically relevant when considering intermittent or adjunctive therapeutic strategies in HS. Furthermore, as the study was conducted under real-world practice conditions, interim visits during treatment or immediately at completion were not systematically scheduled, reflecting routine clinical care where follow-up commonly occurs several weeks after treatment initiation. Finally, a 12-week time point aligns with outcome reporting in many HS studies, facilitating comparison with existing literature. We would also like to note that the 28-day regimen is intentionally selected to reflect the use of tetracyclines for acute flares or as short-term/bridging therapy (e.g., prior to surgery or while awaiting laboratory workup for long-term treatments), thereby avoiding inappropriate prolonged antibiotic use, which does not confer sustained benefit after discontinuation, does not modify disease course, and could contribute to AMR.
Our outcomes outperform those reported in the literature for RR-DC, possibly owing to the milder baseline severity of our cohort, with 14 (21.21%) classified as mild, 45 (68.18%) as moderate, and 7 (10.61%) as severe as per Hurley staging. According to the IHS4 classification, 5 (7.6%) of our patients had mild disease, 13 (19.7%) moderate disease, and 48 (72.7%) severe disease, although the mean (standard deviation [SD]) baseline draining tunnel count was relatively low at 1.49 (2.24). Nevertheless, a significant percentage of patients had recurrence of lesions after 6 months of follow-up.
Given the scarce evidence on the use of MR-DC for the management of HS, and as, to the best of our knowledge, no previous studies have assessed its use in real-world clinical practice, this study was conceived as an exploratory real-world analysis, aiming to provide clinical insights that may help clinical management and to generate hypotheses and support the need for larger studies in future research.
The study limitations include its retrospective and single-center design, the relatively small sample size, the open-label nature of the study, the lack of a placebo arm or washout periods, the short follow-up, and the use of concomitant therapies in some patients, which may have influenced the observed outcomes. Nevertheless, the concomitant treatment regimens were stable for at least 6 months prior to the introduction of MR-DC, reducing the likelihood that observed changes were driven by recent adjustments in background therapy. Many of these limitations are inherent to the real-world clinical practice setting in which the study was conducted.
Conclusion
Despite the limitations of our study, our findings support the short-term use of 40 mg MR-DC as an effective option on an ad hoc basis or managing inflammatory flares in patients with HS, either alone or in combination, under real-life conditions, with a favorable safety profile and providing a lower risk of AE and bacterial resistance. Further studies are warranted to assess its effectiveness, define optimal duration, and identify patients most likely to benefit.
Acknowledgements
We thank the participants of the study. At the time of the study Gemma Camiña-Conforto was affiliated with Hospital de la Santa Creu i Sant Pau. Gemma Camiña-Conforto is no longer affiliated with Hospital de la Santa Creu i Sant Pau and is now affiliated with Complex Universitari Hospitalari Moisès Broggi, Consorci Sanitari Integral, Sant Joan Despí, Barcelona, Spain.
Medical Writing/Editorial Assistance
During the writing of this manuscript, the authors used ChatGPT to check for grammatical mistakes. No funding was received for this assistance. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the publication’s content.
Author Contributions
Gemma Camiña-Conforto contributed to the conception and design of the work; acquisition, analysis, and interpretation of data; drafting of the manuscript; and approved the final version. Luis Puig contributed to the conception and design of the work; analysis and interpretation of data; critical revision of the manuscript; and approved the final version. Eva Vilarrasa contributed to the conception and design of the work; acquisition, analysis and interpretation of data; critical revision of the manuscript; and approved the final version. All authors agree to be accountable for all aspects of the work and ensure its integrity and accuracy.
Funding
No funding or sponsorship was received for this study or publication of this article.
Data Availability
All data generated or analyzed during this study are included in this published article.
Declarations
Conflict of Interest
Gemma Camiña-Conforto has received honoraria as a speaker for Sun Pharma, UCB and LEO Pharma. Luis Puig has perceived consultancy/speaker’s honoraria from and/or participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius Kabi, Galderma, Horizon Therapeutics, Johnson & Johnson, Leo-Pharma, Lilly, Novartis, Pfizer, Samsung Bioepis, Sandoz, Sanofi, STADA, Sun Pharma, and UCB. Eva Vilarrasa has received honoraria as a speaker, consultancies, research support and in participation as an investigator in clinical trials for Abbvie, Aceleryn, Almirall, Amgen, Bayer, Biofrontera, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Citryll, Galderma, Gebro, Incyte, Isdin, Johnson & Johnson, Leo-Pharma, Lilly, Merck-Serono, MSD, Moonlake Inmunotherapeutics, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB. Eva Vilarrasa and Luis Puig are Editorial Board members of Dermatology and Therapy. Eva Vilarrasa and Luis Puig were not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.
Ethical Approval
This study was approved by the Hospital Ethics Committee (protocol code IIBSP-DOX-2024-9), which waived the requirement for informed consent to conduct the study because of the retrospective nature of data collection from routine practice records. This investigation complied with Good Clinical Practice standards and the International Council for Harmonization directives, as well as the ethical principles outlined in the Declaration of Helsinki. All data were anonymized prior to analysis.
Footnotes
Prior Presentation: Preliminary results of this study, including a smaller patient cohort, were previously presented as a poster (P-122) at the European Hidradenitis Suppurativa Foundation (EHSF) Congress 2023 in Florence, Italy, February 8–10, 2023 and as an oral presentation at the 50th National Congress of Dermatology held in Santiago de Compostela, Spain, May 10–13, 2023.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Zouboulis CC, Desai N, Emtestam L, et al. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol Venereol. 2015;29(4):619–44. 10.1111/jdv.12966. [DOI] [PubMed] [Google Scholar]
- 2.Zouboulis CC, Bechara FG, Benhadou F, et al. European S2k guidelines for hidradenitis suppurativa/acne inversa part 2: treatment. J Eur Acad Dermatol Venereol. 2025;39(5):899–941. 10.1111/jdv.20472. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Navarro-Triviño FJ, Pérez-López I, Ruiz-Villaverde R. Doxycycline, an antibiotic or an anti-inflammatory agent? The most common uses in dermatology. Actas Dermosifiliogr. 2020;111(7):561–6. 10.1016/J.AD.2019.12.006. [DOI] [PubMed] [Google Scholar]
- 4.Bettoli V, Manfredini M, Massoli L, et al. Rates of antibiotic resistance/sensitivity in bacterial cultures of hidradenitis suppurativa patients. J Eur Acad Dermatol Venereol. 2019;33(5):930–6. 10.1111/jdv.15332. [DOI] [PubMed] [Google Scholar]
- 5.George S, Muhaj FF, Nguyen CD, Tyring SK. Part I antimicrobial resistance: bacterial pathogens of dermatologic significance and implications of rising resistance. J Am Acad Dermatol. 2022;86(6):1189–204. 10.1016/J.JAAD.2021.11.066. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Kontochristopoulos G, Tsiogka A, Agiasofitou E, et al. Efficacy of subantimicrobial, modified-release doxycycline compared to regular-release doxycycline for the treatment of hidradenitis suppurativa. Skin Appendage Disord. 2022;8(6):476–81. 10.1159/000524762. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Moore A, Ling M, Bucko A, et al. Efficacy and safety of subantimicrobial dose, modified-release doxycycline 40 mg versus doxycycline100 mg versus placebo for the treatment of inflammatory lesions in moderate and severe acne: a randomized, double-blinded, controlled study. J Drugs Dermatol. 2015;14(6):581–6. [PubMed] [Google Scholar]
- 8.van Straalen KR, Tzellos T, Guillem P, et al. The efficacy and tolerability of tetracyclines and clindamycin plus rifampicin for the treatment of hidradenitis suppurativa: results of a prospective European cohort study. J Am Acad Dermatol. 2021;85(2):369–78. 10.1016/j.jaad.2020.12.089. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data generated or analyzed during this study are included in this published article.