Publications

Psoriasis is a systemic, relapsing, inflammatory disease associated with serious comorbidities including mood problems and/or unhealthy lifestyle behaviours. Cutaneous and systemic abnormalities in innate and acquired immunity play a role in its pathogenesis. The exact pathogenetic mechanism remains elusive. Evidence is accumulating that TNF-alpha, IL-17 and IL-23 signalling are highly relevant as targeting these pathways reduces disease activity. Evidence suggests a strong link between psoriasis and depression in adults. The International Psoriasis Council (IPC) held a roundtable event, "Psoriasis and Mental Health", in Barcelona, Spain which focused on the presence of depression and suicidality, plus the role of neuroinflammation in psoriasis, sleep disruption and the impact of depression on cardiovascular disease outcomes. We summarize here the expert presentations to provide additional insight into the understanding of psychiatric comorbidities of psoriasis and of the impact of chronic, systemic inflammation on neuro- and cardiovascular outcomes. the associations between psoriasis and other psychiatric comorbidities are still controversial and warrant further attention.

Hidradenitis suppurativa (HS; also designated as acne inversa) is a chronic inflammatory disorder, which affects the intertriginous skin and is associated with numerous systemic comorbidities. The estimated prevalence of HS is  1% in most studied countries. Typically starting in early adulthood, cutaneous inflamed nodules, abscesses and pus-discharging tunnels develop in axillary, inguinal, gluteal and perianal body sites. The comorbidities of HS include metabolic and cardiovascular disorders, which contribute to reduced life expectancy. A genetic predisposition, smoking, obesity and hormonal factors are established aetiological factors for HS. Cutaneous changes seem to start around hair follicles and involve activation of cells of the innate and adaptive immune systems, with pivotal roles for pro-inflammatory cytokines such as tumour necrosis factor, IL-1β and IL-17. The unrestricted and chronic immune response eventually leads to severe pain, pus discharge, irreversible tissue destruction and scar development. HS has profound negative effects on patients' quality of life, which often culminate in social withdrawal, unemployment, depression and suicidal thoughts. The therapeutic options for HS comprise antibiotic treatment, neutralization of tumour necrosis factor and surgical intervention together with lifestyle modification. Nevertheless, there is an enormous need for awareness of HS, understanding of its pathogenesis and novel treatments.

BACKGROUND: Long-term maintenance treatment is required for patients with psoriasis.

OBJECTIVES: To evaluate the efficacy and safety of guselkumab in patients with moderate to severe psoriasis through 3 years of treatment.

METHODS: In 2 ongoing, phase 3 trials of guselkumab (VOYAGE 1 and VOYAGE 2), the proportions of patients achieving at least 90% and 100% improvement in the Psoriasis Area and Severity Index (PASI 90 and PASI 100, respectively) and Investigator's Global Assessment (IGA) scores of 0/1 and 0 were summarized for the guselkumab group (including placebo-to-guselkumab crossover). Patients who met treatment failure rules were considered nonresponders. Safety outcomes (rates/100 patient-years [PY]) were evaluated based on data pooled across studies through week 156.

RESULTS: Three-year response rates for the guselkumab group in VOYAGE 1 and VOYAGE 2, respectively, were 82.8% and 77.2% for PASI 90, 50.8% and 48.8% for PASI 100, 82.1% and 83.0% for IGA score of 0/1, and 53.1% and 52.9% for IGA score of 0. Safety event rates across studies occurred through week 156 as follows: serious adverse events, 5.68/100 PY; serious infections, 1.15/100 PY; nonmelanoma skin cancers, 0.28/100 PY; malignancies other than nonmelanoma skin cancer, 0.47/100 PY; and major adverse cardiovascular events, 0.28/100 PY. Week 156 and week 100 rates were consistent.

LIMITATIONS: There was no comparator arm beyond 1 year.

CONCLUSIONS: Guselkumab shows durable efficacy and a consistent safety profile in patients with moderate to severe psoriasis treated for up to 3 years.

Introduction: Hidradenitis suppurativa (HS) is a chronic skin disorder characterized by inflammatory nodules, abscesses, and fistulae. Patients tend to present in young adulthood and are predominantly female. The pathogenesis of HS involves apopilosebaceous gland follicle occlusion and affected areas often occur where this type of gland predominates. Treatment selection depends on HS severity, which is included in different scoring systems. In recent years, biological therapies have been evaluated and used with increasing frequency in moderate-to-severe HS disease.Areas covered: This review focuses on biological therapies for HS as assessed in case reports, case series, and clinical trials. The efficacy, hidradenitis suppurativa scoring systems, and long-term results of these therapies are discussed depending on the studies' endpoints.Expert opinion: Adalimumab is currently the only FDA-approved HS biological therapy. Some patients do not experience treatment efficacy with adalimumab at 40 mg/week, which may result in increasing the dose or seeking other treatments. Infliximab is the next line of HS treatment with demonstrated efficacy. Other biological therapies being studied have demonstrated efficacy in small patient groups, but lack study power. Further studies may provide answers to seeking treatment options for patients who fail to improve on current standard HS treatment.

BACKGROUND: Methotrexate is an immunomodulatory therapy that may offer benefit to patients with hidradenitis suppurativa (HS). Despite its theoretical advantages, there is a paucity of available data regarding long-term methotrexate use in patients with HS.

OBJECTIVE: This study aimed to assess whether methotrexate treatment leads to improvement in HS disease severity.

METHODS: We conducted an institutional review board-approved, single-center, retrospective chart review of patients with HS who were treated with methotrexate between 2000 and 2018. Primary outcome measurements included the HS Physician's Global Assessment (HS PGA), Hurley staging, abscess count, fistula count, and inflammatory nodule count.

RESULTS: A total of 29 patients were identified; 14 were excluded for reasons including never starting methotrexate and missing follow-up data. For remaining patients (n = 15), the average cumulative dose of methotrexate was 520.1 mg (range, 30-1665 mg) and the average length of treatment was 11.7 months (range, 1-38 months). Patients taking methotrexate as a primary therapy had a higher cumulative dose and length of treatment (520.13 mg; 14.6 months) compared with those taking biologics concomitantly (468.44 mg; 9.1 months). Patients using methotrexate as primary therapy demonstrated nonsignificant reductions in HS PGA, inflammatory nodule count, and abscess count. Patients on concomitant biologic therapy failed to demonstrate any change in HS PGA, inflammatory nodule count, and abscess count.

LIMITATIONS: Limitations of the study include its retrospective nature, small sample size, length of time on methotrexate between groups, and homogeneity of the patient population.

CONCLUSION: Methotrexate may represent an effective treatment option in older patients with lower body mass indices but fails to offer benefit in patients taking concurrent biologic therapy.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory, skin condition associated with many comorbidities and often has a substantial impact on patients' lives.

OBJECTIVES: To evaluate symptom burden and health-related quality of life (HRQoL) at baseline in patients with HS in an observational, real-world, clinical setting using several tools including a validated HS-specific instrument.

METHODS: This study evaluated HRQoL data from the international UNITE HS disease registry. Administration of patient-reported outcome (PRO) instruments and collection of data were executed per local regulations. All data were assessed using descriptive statistical methods.

RESULTS: PRO data from 529 adults and 65 adolescents were evaluated. Most adults (64.5%) and adolescents (73.8%) were classified as Hurley Stage II with substantial disease burden at baseline. HS had a large effect (mean DLQI = 12.6) and moderate effect (mean CDLQI = 6.9) on the lives of adults and adolescents, respectively. Approximately 58% of adults and 41% of adolescents had anxiety scores beyond the normal range; 30% of adults and 16% of adolescents exhibited symptoms of depression. Based on HSSA and HSIA scores, approximately 30% of adults reported a substantial burden of multiple HS clinical symptoms and more than 45% reported a significant emotional impact of HS that adversely affected their intimate relationships. Only 60% of adults were employed and of those, 64% reported at least some degree of impairment while working because of HS.

CONCLUSIONS: Based on PROs collected from patients enrolled in the UNITE registry, a real-world, clinical setting, HS has a significant negative impact on the everyday lives of patients affected by this disease.

Many women report improvement in psoriasis during pregnancy; others report that psoriasis becomes worse during pregnancy. Balancing effective management of psoriasis against potential risk in pregnancy is important, especially because the severity of psoriasis can have an impact on the pregnancy experience and possibly the outcome. This article discusses current understanding of pregnancy risk profiles of medications used to treat psoriasis.

BACKGROUND: Chronic psoriasis may require medication adjustments over time.

OBJECTIVES: To evaluate the efficacy/safety of tildrakizumab in subgroups from the reSURFACE studies (N = 1862) that received continuous dosing, higher/lower dosing, treatment interruption/reinitiation and initiation.

METHODS: Responders [Psoriasis Area and Severity Index (PASI) ≥ 75%] and partial responders (PASI ≥ 50% to < 75%) in Part 3 of the reSURFACE studies (weeks 28-52 or week 64) who received tildrakizumab 200 mg or 100 mg were rerandomized to the same dosage (T100/T100 or T200/T200), a higher/lower dosage (T100/T200 or T200/T100) or placebo (PBO) (T100/PBO or T200/PBO). Patients receiving PBO who relapsed were reinitiated to tildrakizumab. Etanercept (ETN) week-28 partial responders and nonresponders (PASI < 50%) received tildrakizumab 200 mg (ETN/T200).

RESULTS: Among T100/T100 and T200/T200 week-28 partial responders, the proportion of patients who achieved as-observed PASI 75 responses increased over time. Among T100/T200 week-28 partial responders, PASI 75 responses increased from week 32 (38·5%) to week 52 (63·2%) and remained consistent in T200/T100 week-28 responders. Among patients who relapsed in the T100/PBO and T200/PBO groups, 86% and 83% of those who reinitiated tildrakizumab achieved PASI 75 by week 64, respectively. Among ETN/T200 week-28 partial responders, PASI 75 responses (nonresponder imputation) increased from week 32 (24·1%) to week 52 (74·7%). PASI 90, PASI 100 and Physician's Global Assessment responses were consistent with PASI 75 results. Treatment was well tolerated.

CONCLUSIONS: Patients generally fared well with tildrakizumab maintenance, reinitiation, dose adjustment or initiation. What's already known about this topic? Tildrakizumab demonstrated significant efficacy vs. placebo with a positive safety profile during the first 28 weeks of treatment in two randomized double-blind trials. What does this study add? Treatment scenarios with tildrakizumab, such as long-term continuous dosing (up to 64 weeks), treatment interruption/reinitiation and switching from another biologic, can be part of the management of plaque psoriasis with a reasonable expectation of efficacy and tolerability.