Background:. Females and minorities have been underrepresented in clinical research despite legislative efforts, including in hidradenitis suppurativa (HS) and psoriasis (PsO) clinical trials. Objective:. To identify differences in demographic breakdowns of HS and PsO patients between health care settings to uncover any causative health disparities. Methods:. This study reports racial, ethnic, and sex of HS and PsO patient populations across the emergency department (ED), inpatient, clinical trial, and registry settings. In addition, 95% confidence intervals are used as proxies of statistical significance to compare demographics between settings. Results:. Female, Hispanic, and Black patients were underrepresented in HS clinical trials compared to their population prevalence (female: 63.7% vs 73.5%; Hispanic: 3.8% vs 12.0%; Black: 9.1% vs 20.3%). Female and Black patients were underrepresented in PsO trials compared to their population prevalence (female: 33.0% vs 54.8%; Black: 2.2% vs 5.7%). Black patients were overrepresented in the inpatient and ED settings in HS (inpatient vs ED vs population prevalence: 49.9% vs 49.9% vs 20.3%) and in the inpatient setting in PsO (inpatient vs population prevalence: 19.8% vs 5.7%). Limitations:. The main limitation is the reliability and generalizability of the published studies used to compare demographics across settings. Conclusion:. Underrepresentation of females and minorities in HS and PsO clinical trials is consistent with published literature. Overrepresentation of Black patients in acute care settings is likely multifactorial.

Background: In some hidradenitis suppurativa (HS) clinical trial study arms, there is an unexpected decline in efficacy between the penultimate visit and the prespecified primary endpoint week, which we have termed a “wobble.” Objective: We aimed to establish how often study arms in HS programs wobble. Methods: In a retrospective review, we identified HS clinical trials listed on ClinicalTrials.gov testing systemic, nonantibiotic medications that utilized Hidradenitis Suppurativa Clinical Response (HiSCR) as an outcome measure. We identified study arms demonstrating greater improvement in a visit prior to the primary endpoint week. Baseline subject characteristics were compared between studies with HiSCR wobble and no HiSCR wobble. Results: A total of 21 studies (randomized control trial [RCT], n = 14; open-label, n = 7) with 35 study drug arms (RCT, n = 27; open-label, n = 8) and 14 placebo arms were identified. HiSCR wobble occurred significantly more often in RCT compared to open-label study drug arms (11/27 [40.7%] vs 0/8 [0%]). In RCT study arms with HiSCR wobble, baseline draining fistula counts were significantly lower (2.3 vs 3.2), and numerically fewer Hurley stage 3 patients (33.2% vs 42.5%), lower weighted total abscess and nodule counts (12.1 vs 12.6), lower weighted dermatology life quality index scores (12.5 vs 14.5), and a higher proportion of female patients (63.9% vs 58.3%) were observed. Limitations: Include low number of HS clinical trials and insufficient data reported in many studies to assess for wobble, degree of wobble, and to compare all baseline characteristics. Conclusion: Nonlinear improvement in study arm response occurs in some HS RCTs. Potential contributing factors include a higher proportion of less severe patients at baseline and more female patients.

International Journal of DermatologyEarly View Correspondence Treatment of necrobiosis lipoidica with secukinumab (Cosentyx): a case series Ruby S. Gibson MD, Ruby S. Gibson MD Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USASearch for more papers by this authorPrerna Salian MPH, Prerna Salian MPH Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USASearch for more papers by this authorAshley Beckles BS, Ashley Beckles BS Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USASearch for more papers by this authorRobert Stavert MD, MBA, Robert Stavert MD, MBA Science 37, Durham, NC, USASearch for more papers by this authorSteven Tahan MD, Steven Tahan MD Harvard Medical School, Boston, MA, USA Division of Anatomic Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USASearch for more papers by this authorAlexa B. Kimball MD, MPH, Alexa B. Kimball MD, MPH Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School, Boston, MA, USASearch for more papers by this authorMartina L. Porter MD, Corresponding Author Martina L. Porter MD [email protected] Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School, Boston, MA, USASearch for more papers by this author Ruby S. Gibson MD, Ruby S. Gibson MD Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USASearch for more papers by this authorPrerna Salian MPH, Prerna Salian MPH Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USASearch for more papers by this authorAshley Beckles BS, Ashley Beckles BS Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USASearch for more papers by this authorRobert Stavert MD, MBA, Robert Stavert MD, MBA Science 37, Durham, NC, USASearch for more papers by this authorSteven Tahan MD, Steven Tahan MD Harvard Medical School, Boston, MA, USA Division of Anatomic Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USASearch for more papers by this authorAlexa B. Kimball MD, MPH, Alexa B. Kimball MD, MPH Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School, Boston, MA, USASearch for more papers by this authorMartina L. Porter MD, Corresponding Author Martina L. Porter MD [email protected] Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA Harvard Medical School, Boston, MA, USASearch for more papers by this author First published: 01 July 2023 https://doi.org/10.1111/ijd.16780 Conflict of interest: Dr. Kimball is a consultant and investigator for Abbvie, AnaptysBio, Bristol Meyers Squibb, ChemoCentryx, Janssen, Eli Lilly, Moonlake, Novartis, Pfizer, and UCB, Incyte; consultant for Regeneron, Alumis, Amgen, Priovant, Sanofi, Sonoma, Ventyx, and Bayer, receives fellowship funding from Janssen and Abbvie; and Board of Directors for Almirall. Dr. Porter is a consultant and/or investigator for Abbvie, Bristol Meyers Squibb, Janssen, Eli Lilly, Moonlake, Novartis, Pfizer, Trifecta Clinical (on behalf of acelyrin), UCB, Aristea, Regeneron, Innovoderm, Bayer, and Incyte. Dr. Gibson's fellowship was funded through the National Psoriasis Foundation. Dr. Gibson is an investigator for Abbvie, Janssen, Regeneron, Eli Lilly, Novartis, UCB, Aristea, Incyte, Innovoderm, Bayer, and Moonlake. Drs. Tahan and Stavert, Ms. Salian, and Ms. Beckles have no financial relationships or conflicts of interest relevant to this article to disclose. Funding source: The study was funded by Novartis, and medication was provided at no cost for this study. They approved the manuscript and the decision to submit for publication. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Open Research Data availability statement The data that support the findings of this study are available from the corresponding author, MP, upon reasonable request. References 1Wakusawa C, Fujimura T, Kambayashi Y, Furudate S, Hashimoto A, Aiba S. Pigmented necrobiosis lipoidica accompanied by insulin-dependent diabetes mellitus induces CD163+ proinflammatory macrophages and interleukin-17-producing cells. Acta Derm Venereol. 2013; 93(4): 475–6. https://doi.org/10.2340/00015555-1502 2Foss C, Clark A, Inabinet R, Camacho F, Jorizzo J. An open-label pilot study of alefacept for the treatment of pyoderma gangrenosum. J Eur Acad Dermatol Venereol. 2008; 22(8): 943–9. https://doi.org/10.1111/J.1468-3083.2008.02680.X 3Wilson D, Hockenberry MJ, Wong DL. Wong's clinical manual of pediatric nursing. 7th ed. St. Louis, Mo: Mosby Elsevier; 2008. 4Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)—a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994; 19(3): 210–6. https://doi.org/10.1111/J.1365-2230.1994.TB01167.X 5Gottlieb AB, Wu JJ, Griffiths CEM, Marfo K, Muscianisi E, Meng X, et al. Clinical efficacy and safety of secukinumab in patients with psoriasis and comorbidities: pooled analysis of 4 phase 3 clinical trials. J Dermatol Treat. 2020; 33(3): 1482–90. https://doi.org/10.1080/09546634.2020.1832187 Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

The IL-17 pathways are involved in the pathophysiology of many inflammatory skin conditions, including hidradenitis suppurativa. Secukinumab, an IL-17A inhibitor, has been used for years in inflammatory skin disorders such as psoriasis. To date, the only US FDA-approved medication for hidradenitis suppurativa is adalimumab, a TNF-α inhibitor. Recently, secukinumab has demonstrated promising results in the treatment of hidradenitis suppurativa in the phase III SUNSHINE and SUNRISE clinical trials. This article reviews the mechanism of action of secukinumab and summarizes the available clinical efficacy and safety data regarding secukinumab in the management of hidradenitis suppurativa.

The inflammatory pathophysiology of hidradenitis suppurativa (HS) is not yet clearly defined. Despite the lack of disease specificity, inflammatory markers such as Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are used to detect acute and monitor chronic inflammatory conditions.1Lapić I. Padoan A. Bozzato D. Plebani M. Erythrocyte sedimentation rate and C-reactive protein in acute inflammation.Am J Clin Pathol. 2020; 153: 14-29https://doi.org/10.1093/ajcp/aqz142Crossref PubMed Scopus (37) Google Scholar Although CRP has historically been used as an inflammatory marker for HS, ESR may be a more reliableindicator of HS disease severity. Rouleaux formation occurs when many positively charged plasma proteins neutralize negatively charged RBCs and allow for faster erythrocyte aggregation, which further leads to ESR elevations.1Lapić I. Padoan A. Bozzato D. Plebani M. Erythrocyte sedimentation rate and C-reactive protein in acute inflammation.Am J Clin Pathol. 2020; 153: 14-29https://doi.org/10.1093/ajcp/aqz142Crossref PubMed Scopus (37) Google Scholar ESR is affected by physiologic conditions that alter the size or shape or number of red blood cells, fibrinogen concentration, or acute and nonacute phase reaction protein (immunoglobulins) concentrations.1Lapić I. Padoan A. Bozzato D. Plebani M. Erythrocyte sedimentation rate and C-reactive protein in acute inflammation.Am J Clin Pathol. 2020; 153: 14-29https://doi.org/10.1093/ajcp/aqz142Crossref PubMed Scopus (37) Google Scholar ESR can remain elevated for days to weeks after an acute insult.1Lapić I. Padoan A. Bozzato D. Plebani M. Erythrocyte sedimentation rate and C-reactive protein in acute inflammation.Am J Clin Pathol. 2020; 153: 14-29https://doi.org/10.1093/ajcp/aqz142Crossref PubMed Scopus (37) Google Scholar In contrast, CRP is synthesized in response to cytokines, has a short half-life, and normalizes within days after an insult; therefore, it is frequently used to determine any reinfection. Further, the elevated CRP levels have been associated with tissue damage, malignancy, trauma, autoimmune diseases, and burns.1Lapić I. Padoan A. Bozzato D. Plebani M. Erythrocyte sedimentation rate and C-reactive protein in acute inflammation.Am J Clin Pathol. 2020; 153: 14-29https://doi.org/10.1093/ajcp/aqz142Crossref PubMed Scopus (37) Google Scholar ESR and CRP both correlate to HS disease activity and predict treatment response.2Jiménez-Gallo D. De La Varga-Martínez R. Ossorio-Garciá L. Albarrán-Planelles C. Rodríguez C. Linares-Barrios M. The clinical significance of increased serum proinflammatory cytokines, C-reactive protein, and erythrocyte sedimentation rate in patients with hidradenitis suppurativa.Mediators Inflamm. 2017; 2017: 2450401https://doi.org/10.1155/2017/2450401Crossref PubMed Scopus (51) Google Scholar,3Cao Y. Hong F. Conlon D.M. et al.Potential predictive biomarkers of adalimumab response in patients with hidradenitis suppurativa.Br J Dermatol. 2021; 185: 804-814https://doi.org/10.1111/BJD.20097Crossref PubMed Google Scholar It is not surprising that the high burden of inflammation in HS causes a release of positively charged interleukins and other acute reactive proteins that promote erythrocyte aggregation, thus increasing the ESR. In addition, HS is sometimes complicated by anemia of chronic disease, which independently can increase ESR, as decreased red blood cells affect the laboratory measurements. Leukocytosis and thrombocytosis have also been associated with HS, and thrombocytosis is independently associated with elevated ESR.4Kanya P. Rattarittamrong E. Wongtakan O. et al.Platelet function tests and inflammatory markers for the differentiation of primary thrombocytosis and secondary thrombocytosis.Asian Pac J Cancer Prev. 2019; 20: 2079-2085https://doi.org/10.31557/APJCP.2019.20.7.2079Crossref PubMed Scopus (4) Google Scholar CRP is elevated in response to only cytokines in an inflammatory state, whereas ESR can be increased in response to multiple factors related to HS including anemia, leukocytosis, and inflammation. This supports the theory that ESR would be more reflective of HS inflammatory state. Consistent with this hypothesis, Jiménez-Gallo et al2Jiménez-Gallo D. De La Varga-Martínez R. Ossorio-Garciá L. Albarrán-Planelles C. Rodríguez C. Linares-Barrios M. The clinical significance of increased serum proinflammatory cytokines, C-reactive protein, and erythrocyte sedimentation rate in patients with hidradenitis suppurativa.Mediators Inflamm. 2017; 2017: 2450401https://doi.org/10.1155/2017/2450401Crossref PubMed Scopus (51) Google Scholar compared CRP levels and ESR in patients with HS and found ESR elevation at earlier or lower inflammatory states, whereas CRP required a higher inflammatory state. ESRs was significantly elevated in both the moderate (Hidradenitis Suppurativa Physician's Global Assessment scale [HS-PGA 3]) and high (HS-PGA 4 and 5) inflammatory activity categories compared with non-HS controls. In contrast, the CRP levels were only significantly elevated in high inflammatory activity (HS-PGA 4 and 5) compared with non-HS controls. Lastly, the rheumatology and gastroenterology literature has shown that baseline CRP levels can be affected by CRP autoantibodies or CRP genetic polymorphisms.5Enocsson H. Gullstrand B. Eloranta M.L. et al.C-reactive protein levels in systemic lupus erythematosus are modulated by the interferon gene signature and CRP gene polymorphism rs1205.Front Immunol. 2021; 11: 622326https://doi.org/10.3389/fimmu.2020.622326Crossref PubMed Scopus (13) Google Scholar These factors do not affect ESR and may affect the reliability of elevated CRP as a biomarker of disease activity. In conclusion, the frequently concomitant hematologic abnormalities that also independently elevate ESR and the demonstrated ability of ESR to detect mild HS disease suggest that ESR may be a superior marker of HS disease activity. Further research is needed to investigate and compare the inflammatory markers in HS. Dr Kimball is a consultant and investigator for Abbvie, Bristol Meyers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Incyte; consultant for Regeneron and Bayer, receives fellowship funding from Janssen and Abbvie; and a member of the board of directors for Almirall. Dr Porter is a consultant and/or investigator for Abbvie, Bristol Meyers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Incyte. Dr Gibson's fellowship was funded through the National Psoriasis Foundation. The authors have no other financial relationships or conflicts of interest relevant to this article to disclose.

Introduction Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disorder characterized by painful nodules, abscesses, fistulae, and scarring with a predilection for flexural regions. Several biologics and small molecule inhibitors are being evaluated in clinical trials for treatment. Areas covered The authors discuss the data available from clinical trials and smaller, high-quality studies for existing and emerging biologic and small molecule inhibitor therapies for treatment of HS. Biologics discussed include TNF alpha, IL-17, IL-23, IL-12/23, and IL-1 inhibitors. Small molecule inhibitors discussed include PDE4, JAK, TYK, IFX-1, and complement cascade inhibitors. Pharmacokinetics and pharmacodynamics for these drugs are also described. Expert opinion Trial data and our own experience have shown that about half of HS patients experience improvement with adalimumab. However, there is a significant need for pharmacotherapies with higher efficacy goals as in those used for psoriasis. Many biologics and small molecule inhibitors are being tested in clinical trials. The landscape of upcoming therapies for hidradenitis suppurativa appears promising.

Hidradenitis suppurativa (HS) is a severe and painful chronic dermatologic condition affecting hair follicles with a significant negative impact on patient quality of life. Effective treatment of HS has proven challenging and often involves multiple modalities. These include topical treatments, systemic antibiotics, retinoids, hormonal therapies, biologic and nonbiologic immunosuppressants, small molecule inhibitors, surgery, and photodynamic/radiation therapy. This review outlines the nonbiologic systemic therapies for HS and describes the latest research on these therapies. Therapies covered in this review include systemic antibiotics, retinoids, hormonal therapies, nonbiologic immunosuppressants, and small molecule inhibitors.

In the SOLACE study, Gulliver et al.1 evaluate the real-world effectiveness of adalimumab, the first, and, to date, only medication approved for treatment of hidradenitis suppurativa (HS), a debilitating condition characterized by recurrent inflammatory nodules, abscesses, and fistulas. In this large open-label cohort of 138 patients treated with adalimumab, 68.9% achieved HiSCR (a 50% reduction in inflammatory lesion counts) at week 24, higher than the results seen in the PIONEER studies at week 12. Patients with medium to high inflammatory lesion counts (abscesses and inflammatory nodules AN) counts experienced the best response. During the pivotal adalimumab clinical trials, primary endpoints were based on the HiSCR,2 a measure that was analytically derived from the convergence of clinical and patient-reported data in an adalimumab trial. HiSCR does not incorporate improvements in fistulae. Since then, additional tools have emerged including the International HS Severity Score System (IHS4)3 which designates higher weights to draining fistulas and abscesses and, therefore, measures something different than HiSCR. As there is an overlap in the measures, it is not surprising that Gulliver et al. demonstrated that HiSCR responders also had a decrease in IHS4 scores. The best IHS4 responders were those with high AN counts, which seem most responsive to adalimumab. This finding is consistent with work by Frew et al.,4 who did not demonstrate a significant change in the IHS4 category when retrospectively applying the IHS4 to the PIONEER 1 data. Fistulas are an extremely important part of HS, and better treatment options as well as ways to measurement the impact of improvement may still emerge. In the meantime, it seems reasonable to use both scores. It is hard to get HS under control. The first studies with adalimumab showed successful treatment required relatively high doses. Taking into account the open-label design and some population differences, this study confirms that a long duration of treatment may be important to achieve desired clinical effect: the proportion of patients who achieved HiSCR increased from 69% at week 24 to 82% and 75% at week 52 for patients.2 It is difficult to maintain placebo groups past a few months in placebo controlled studies. Given the advances in the field, now is the time to move into an era with more head-to-head comparisons, which will also allow the use of longer primary endpoints. In the meantime, the guidance that it takes time to attain desired effects with adalimumab and other treatments is important for patients and physicians. HS is still hard to treat, but we are continuing to improve both our approach and our results. Dr. Kimball is a consultant and investigator for Abbvie, Bristol Meyers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Incyte; consultant for Regeneron and Bayer, receives fellowship funding from Janssen and Abbvie; and is on the Board of Directors of Almirall. None.