Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis-a randomized controlled trial (PSORRO).

Background: Roflumilast is a targeted inhibitor of phosphodiesterase (PDE)-4 and has been approved for treatment of severe chronic obstructive pulmonary disease for more than a decade. Generic versions are available in the United States. PDE-4 is involved in the psoriasis pathogenesis, but the efficacy and safety of oral roflumilast in patients with psoriasis have not previously been studied. Methods: A company-independent, multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.govNCT04549870). Patients were randomized 1:1 to receive monotherapy with oral roflumilast 500 µg once daily or placebo. At week 12, placebo patients were switched to open-label roflumilast through week 24. The primary endpoint was a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI75) at week 12. Findings: In all, 46 patients were randomized (roflumilast, n = 23; placebo, n = 23). At week 12, significantly more patients in the active arm achieved PASI75 (8 of 23 patients [35%]) vs. placebo (0 of 23 patients [0%], with a difference vs. placebo of 8 [35%] patients, 95% CI: 3 [13%]-13 [57%] patients) (p = 0.014). At week 24, 15 (65%), 10 (44%), 5 (22%), and 2 (9%) of patients treated with roflumilast from week 0 had PASI50, PASI75, PASI90, and PASI100 responses (key secondary endpoints), respectively. The most prevalent, drug-related adverse events in both treatment groups were transient gastrointestinal symptoms, weight-loss, headache, and insomnia. A total of three patients (roflumilast n = 2; placebo, n = 1) discontinued therapy due to adverse events. Interpretation: Oral roflumilast was efficacious and safe in treating moderate-to-severe plaque psoriasis over 24 weeks. With generic versions available, this drug may represent an inexpensive and convenient alternative to established systemic psoriasis treatments. Funding: Financial support was received from Herlev and Gentofte Hospital, University of Copenhagen, and independent grants from private foundations in Denmark. No pharmaceutical company, including the market authorization holder of roflumilast, was involved in the study at any point.

Adalimumab for the Treatment of Periodontitis in a 35-Year-Old Woman with Hidradenitis Suppurativa.

Increasing evidence suggests an association between chronic inflammatory conditions and oral health. Herein, we present a case of a 35-year-old woman with concomitant hidradenitis suppurativa (HS) and periodontitis, who was treated successfully with adalimumab. After 3 months of treatment, a marked improvement was observed in her clinical scores of HS, quality of life, as well as her gingival pain and signs of inflammation. This finding calls for a closer collaboration between dermatologists and dentists to further explore the possible beneficial role of biologic therapy for chronic inflammatory skin conditions as well as periodontitis.

Influence of Genetics, Immunity and the Microbiome on the Prognosis of Inflammatory Bowel Disease (IBD Prognosis Study): the protocol for a Copenhagen IBD Inception Cohort Study.

INTRODUCTION: Inflammatory bowel diseases (IBD), encompassing Crohn's disease and ulcerative colitis, are chronic, inflammatory diseases of the gastrointestinal tract. We have initiated a Danish population-based inception cohort study aiming to investigate the underlying mechanisms for the heterogeneous course of IBD, including need for, and response to, treatment. METHODS AND ANALYSIS: IBD Prognosis Study is a prospective, population-based inception cohort study of unselected, newly diagnosed adult, adolescent and paediatric patients with IBD within the uptake area of Hvidovre University Hospital and Herlev University Hospital, Denmark, which covers approximately 1 050 000 inhabitants (~20% of the Danish population). The diagnosis of IBD will be according to the Porto diagnostic criteria in paediatric and adolescent patients or the Copenhagen diagnostic criteria in adult patients. All patients will be followed prospectively with regular clinical examinations including ileocolonoscopies, MRI of the small intestine, validated patient-reported measures and objective examinations with intestinal ultrasound. In addition, intestinal biopsies from ileocolonoscopies, stool, rectal swabs, saliva samples, swabs of the oral cavity and blood samples will be collected systematically for the analysis of biomarkers, microbiome and genetic profiles. Environmental factors and quality of life will be assessed using questionnaires and, when available, automatic registration of purchase data. The occurrence and course of extraintestinal manifestations will be evaluated by rheumatologists, dermatologists and dentists, and assessed by MR cholangiopancreatography, MR of the spine and sacroiliac joints, ultrasonography of peripheral joints and entheses, clinical oral examination, as well as panoramic radiograph of the jaws. Fibroscans and dual-energy X-ray absorptiometry scans will be performed to monitor occurrence and course of chronic liver diseases, osteopenia and osteoporosis. ETHICS AND DISSEMINATION: This study has been approved by Ethics Committee of the Capital Region of Denmark (approval number: H-20065831). Study results will be disseminated through publication in international scientific journals and presentation at (inter)national conferences.

The road to biologics in patients with hidradenitis suppurativa: a nationwide drug utilization study.

BACKGROUND: Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's treatment journey leading to biologic therapy is unclear. OBJECTIVES: To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy. METHODS: We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients' treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variables. RESULTS: A total of 225 patients with HS were included. Patients had most frequently been treated with penicillin (n = 214; 95·1%), dicloxacillin (n = 194; 86·2%), tetracycline (n = 145; 64·4%) and rifampicin/clindamycin (n = 111; 49·3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4·0 (SD 1·3) different systemic therapies, across a mean of 16·9 (SD 11·3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15·3 (SD 5·1) years [8·2 (SD 5·9) years when excluding penicillin and dicloxacillin]. CONCLUSIONS: Patients with HS who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression. What is already known about this topic? The treatment journey leading to biologic therapy in patients with HS has not previously been investigated. What does this study add? Our data from 225 patients with HS illustrate that patients who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS.

Drug Survival of Biologics in Patients With Hidradenitis Suppurativa.

IMPORTANCE: Biologics are important in treating patients with hidradenitis suppurativa (HS). However, to our knowledge, data on their real-life performance and treatment patterns in HS are limited. OBJECTIVE: To examine the drug survival of biologic therapies for HS in a real-world setting. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included all patients with HS between January 1, 2005, and December 31, 2018, who were treated with biologics at the 5 academic hospital clinics where all biologic treatment for HS is conducted in Denmark. Biologics included adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, secukinumab, and ustekinumab. Data were analyzed between June 1, 2021, and June 20, 2021. MAIN OUTCOMES AND MEASURES: Drug survival was depicted through Kaplan-Meier curves, and Cox regression models were used to calculate adjusted (age, sex, previous number of biologic treatment series) hazard ratios (aHRs) with 95% CIs for the risk of treatment discontinuation. Switching patterns were visualized through a Sankey diagram. RESULTS: The study comprised 241 patients (176 women [61.8%]; total of 386 treatment series) with a mean (SD) age of 41.8 (12.6) years at initiation of first biologic therapy. There were a total of 256 (189 [73.8%] biologic naive), 66 (32 [48.5%] biologic naive), 23 (9 [39.1%] biologic naive), and 22 (9 [40.9%] biologic naive) treatment series with adalimumab, infliximab, etanercept, and ustekinumab, respectively. The median time to discontinuation was 36.0 (IQR, 21.9-63.0), 28.7 (IQR, 15.1-62.9), 26.0 (IQR, 16.9-155.9), and 17.9 weeks (IQR, 12.9-41.0) for adalimumab, infliximab, ustekinumab and etanercept, respectively. The risk of drug discontinuation was significantly higher for etanercept compared with adalimumab (aHR, 1.81; 95% CI, 1.16-2.82), infliximab (aHR, 1.77; 95% CI, 1.03-3.05), and ustekinumab (aHR, 2.49; 95% CI, 1.12-5.52), whereas no difference was observed when comparing these 3 therapies with each other. We found no significant differences in drug survival for biologic-naive vs nonnaive treatment series. Increasing C-reactive protein levels (aHR, 1.01; 95% CI, 1.00-1.03) and concomitant antibiotic treatment (aHR, 2.82; 95% CI, 1.36-5.86) were associated with the risk of discontinuing infliximab therapy. Men (aHR, 0.69; 95% CI, 0.51-0.91) had a reduced risk of discontinuing use of adalimumab. CONCLUSIONS AND RELEVANCE: In this cohort study, drug survival was comparable between adalimumab, infliximab, and ustekinumab but significantly lower for etanercept. There were no differences in drug survival among biologic-naive and nonnaive patients.

Treatment of hidradenitis suppurativa with tetracycline, doxycycline, or lymecycline: a prospective study.

AIM: To evaluate the clinical efficacy of tetracycline, doxycycline, and lymecycline in patients with hidradenitis suppurativa (HS). METHODS: A prospective study of three different treatment regimens in patients with HS; oral tetracycline 500 mg twice daily, oral doxycycline 100 mg twice daily, and oral lymecycline 300 mg twice daily were administered in patients with HS. Outcomes were change in Hidradenitis Suppurativa Score (HSS), Dermatology Life Quality Life index (DLQI), overall disease-related distress, boil-related pain, number of boils in the preceding month, fraction of patients with no boils in the preceding month, and Physician's Global Assessment (PGA) score at follow-up. RESULTS: In total, 108 patients, 73 (67.6%) women and 35 (32.4%) men, were included. Mean duration of treatment was 4.3 months. The mean HSS at baseline was 26.10 (SD 20.18) points, improving to 17.97 (SD 17.88) at follow-up, difference is 8.13 (95% CI 5.21-10.93), P < 0.0001. Highest improvement in HSS was observed in the tetracycline group. After multivariate adjustment, higher reduction in HSS was significantly associated with lower BMI, Hurley stage III, higher HSS at baseline, and higher number of boils in the preceding month at baseline. CONCLUSION: Oral treatment with tetracycline, doxycycline, and lymecycline appears effective and safe in HS patients. Tetracycline provided the greatest clinical improvement measured by HSS.

Anemia in Patients with Hidradenitis Suppurativa: Prevalence and Risk Factors in a Hospital-Based Cohort.

We examined the prevalence and risk factors of anemia in patients with hidradenitis suppurativa (HS). The presence of anemia and information on risk factors was obtained through interview, clinical examination, and blood samples in a cohort of 367 consecutive patients with HS. The overall prevalence of anemia was 9.3% (11.4% in men and 8.1% in women). Altogether 7.9%, 7.0%, and 20.4% of patients with Hurley stage I, II, and III were anemic, respectively. Risk factors for anemia included increasing age, nonwhite ethnicity, sporadic (nonfamilial) HS, concomitant inflammatory bowel disease (IBD), absence of hypertension, and absence of infected lesions in the preceding month. We found significant inverse correlations between hemoglobin level and inflammatory markers in the blood. There were significant correlations between hemoglobin and lipid levels, and between lipid levels and inflammatory markers. Hemoglobin levels are lower in patients with more severe HS and with more chronic inflammatory burden compared to those with less disease severity. Older age, nonwhite ethnicity, sporadic (nonfamilial) HS, and IBD are the risk factors of anemia.

Biologics for chronic inflammatory skin diseases: an update for the clinician.

The introduction and continuous development in biological drugs has greatly improved the therapeutic quality for patients with chronic inflammatory skin conditions. Current approaches to the biologic treatment of psoriasis, atopic dermatitis, chronic spontaneous urticaria, and hidradenitis suppurativa include licensed use of traditional antitumor necrosis factor agents, selective interleukin antagonists (IL-4, IL-12/23, IL-17), and the IgE inhibitor omalizumab, and as the knowledge on the pathogenesis of these diseases expands, off-label uses of the currently available biologics are becoming increasingly attractive, and the number of investigational drugs is growing progressively plentiful. In recent years, small molecule inhibitors, many of which are used in cancer therapy, have emerged as valuable future prospects in the treatment of inflammatory diseases. Inhibitors of PGD2, JAK, Syk, and C5a all have, to some extent, theorized efficacy in the treatment of chronic skin conditions, and multiple clinical trials are ongoing. The extensive research of the novel targets' roles in the pathogenesis of dermatological conditions should, in the future, further improve the therapeutic options for both the patients and physicians involved.

Factors affecting quality of life in patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) has a substantial impact on patients' lives. We identified factors associated with decreased quality of life (QoL) in patients with HS. Consecutive newly referred patients with HS attending a tertiary referral centre for HS were evaluated with the dermatology life quality index (DLQI). Clinical evaluation was performed according to the Hurley stage. Furthermore, disease duration, number of boils in the past month, boil-associated pain score, overall disease-related distress score, smoking status, employment status and comorbidities were recorded. A total of 339 patients with a mean age of 39.4 years were included; 218 (64.3%) females and 121 (35.7%) males. Of these, 96 (28.3%) had Hurley stage I, whereas 195 (57.5%) and 48 (14.2%) had Hurley II and III, respectively. The mean BMI was 29.0 (SD 7.1) kg/m2 and 75.2% of patients were current or former smokers. The mean overall DLQI score was 11.9 (SD 7.6). After mutual adjustment for clinical characteristics a significant difference in mean overall DLQI score was observed between severity groups (8.6 vs. 12.6 vs. 16.1, adjusted p < 0.001, for Hurley I, II and III, respectively), age group (12.1 vs. 12.1 vs. 12.5 vs. 7.1, adjusted p = 0.002, for ≤ 20, 21-40, 41-60 and > 60 years, respectively), employment status (11.0 vs. 14.6, adjusted p = 0.003, for employed and unemployed, respectively), presence of boils in the preceding month (8.3 vs. 13.6, adjusted p = 0.001, for no boils and presence of boils, respectively), higher overall disease-related distress score (6.3 vs. 13.9, adjusted p < 0.001, for low and high score, respectively), involvement of the groins (8.7 vs. 13.0, adjusted p = 0.035 for no and involvement, respectively), high number of anatomical regions involved (9.8 vs. 12.4 vs. 14.5, adjusted p = 0.007 for 0-1, 2 and ≥ 3 anatomical regions involved, respectively) and diabetes (11.5 vs. 15.2, adjusted p = 0.043, for no and diabetes, respectively). All ten individual DLQI question scores increased significantly with increasing Hurley stage. Patients with HS referred for specialized hospital care report substantial impact on the quality of life. Disease severity (Hurley stage), younger age, diabetes, recent and increasing disease activity and specific anogenital localization are major aggravating factors.

Work productivity and activity impairment in patients with hidradenitis suppurativa: a cross-sectional study.

BACKGROUND: The understanding of absenteeism, presenteeism, and impairments in daily activities among patients with hidradenitis suppurativa (HS) is limited. We examined the impact of disease-specific factors of HS on work and daily life among a cohort of outpatients in a tertiary hospital setting. METHODS: Consecutive patients with HS were clinically evaluated and completed the Work Productivity and Activity Impairment (WPAI) questionnaire modified for HS. RESULTS: A total of 100 patients were included. Among 57 (57.0%) patients who were employed, 21.2% reported missing work, and 60.4% reported loss of work productivity during the preceding week as a result of HS. The overall work productivity was reduced by 26.6%. Seventy-two percent reported daily activity impairment, averaging 32.7% reduction in daily activities. Moderate to strong correlations were observed between reduction in quality of life and the WPAI outcomes; presenteeism, overall work impairment, and activity impairment (r = 0.50-0.77). There were moderate correlations between disease severity and the same outcomes (r = 0.35-0.46). The mean rank of activity impairment among patients with Hurley stage I was 34.8, 60.1 for Hurley stage II, and 64.0 for Hurley stage III, P < 0.0001. Unemployed patients had higher activity impairment compared with employed patients (mean rank: 61.0 vs. 42.6, P = 0.001). CONCLUSION: There are considerable rates of presenteeism, overall work impairment, and activity impairment in HS patients. Presenteeism, loss of overall work productivity, and activity impairment are positively correlated with greater disease severity and reduction in quality of life.

Therapeutic Response to Secukinumab in a 36-Year-Old Woman with Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder involving primarily the intertriginous skin of the axillary, inguinal, genital, and perianal areas of the body. It is characterized by recurrent inflamed nodules and abscesses, resulting in fistulae, fibrosis, and scarring. We present a case of HS refractory to local and systemic antibiotic therapy as well as anti-TNF and anti-IL12/23 that was successfully treated with secukinumab (anti-IL17A).

The role of interleukin-17 in the pathogenesis of hidradenitis suppurativa.

Hidradenitis suppurativa is a chronic inflammatory skin condition affecting primarily the axillary, perianal, and inguinal areas. Patients with hidradenitis suppurativa present with occlusion and subsequent rupture of follicular ducts, profound abscesses, fistulae, odorous discharge, fibrosis, and scar formation, causing significant morbidity. Knowledge of the pathogenesis of hidradenitis suppurativa is limited and treatment with antimicrobial drugs, immunosuppressants, and surgical procedures have shown varying results. The pathogenic role of the interleukin-17 cytokine family in chronic inflammatory skin conditions has been described. Interleukin-17A and interleukin-17F have similar properties and induce the production of cytokines, chemokines, antimicrobial peptides, and metalloproteinases, all of which take part in the inflammatory response. The efficacy of anti-interleukin-17A therapy in psoriasis has also been proven and anti- interleukin-17A drugs are already in use for this condition. There is currently no consensus on the role of interleukin-17 in the pathogenesis of hidradenitis suppurativa. Studies have demonstrated increased interleukin-17 mRNA expression in lesional hidradenitis suppurativa skin, whereas the protein concentrations of interleukin-17 were found to be normal compared to healthy control skin in one other study. A phase II clinical trial on anti- interleukin-17 therapy in hidradenitis suppurativa is ongoing.