Efficacy and safety of tirbanibulin 1% ointment in actinic keratoses: Data from two phase-III trials and the real-life clinical practice presented at the European Academy of Dermatology and Venereology Congress 2022.

BACKGROUND: The 31st European Academy of Dermatology and Venereology (EADV) Congress took place between 7th and 10th of September 2022 in Milan, Italy. OBJECTIVES: We report presented clinical data on the efficacy/effectiveness, safety and tolerability of tirbanibulin 1% ointment that has recently been licensed for actinic keratosis (AK) of the face or scalp in adults. METHODS: Summary of presentations given at the EADV Congress. RESULTS: Prof. Pellacani presented two post hoc analyses from two phase-III trials with AK patients (NCT03285477 [N = 351] and NCT03285490 [N = 351]): A descriptive analysis of medical history, concomitant medications, and safety results confirming a favourable profile for tirbanibulin showing that number of baseline AK lesions was not correlated to severity of local skin reactions. The latter analysis showed that cases of tirbanibulin application site pain or pruritus were few, and most were found to be mild. Prof. Kunstfeld reported six real-life clinical cases in Austria showing good tirbanibulin effectiveness, safety and tolerability for the treatment of new or recurring AK lesions. Results demonstrated that after 2- to 4-month follow-up, tirbanibulin was well tolerated and effective in AK patients. Presentations by Dr. Patel confirmed good outcomes and tolerability of tirbanibulin in Olsen grade 1-2 AK (N = 12) and porokeratosis patients (N = 4) treated once daily for 5 consecutive days in the United Kingdom. Furthermore, real-world experience in solid organ transplant recipients (N = 2) demonstrated effectiveness of tirbanibulin in skin field cancerization treatment. A symposium sponsored by Almirall was conducted during the congress in which Dr. Hadshiew and Dr. Lear brought together their clinical experience in Germany and the United Kingdom respectively. Interesting clinical cases of 5 consecutive days of tirbanibulin treatment compared to other treatments were discussed with attendees, as well as current treatment needs of AK patients. CONCLUSIONS: This article provides an overview of presentations and symposium discussions, summarizing key phase-III results and real-life clinical experience with tirbanibulin shared by dermatologists across Europe.

Long-term safety of risankizumab from 17 clinical trials in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Risankizumab has demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis in randomized clinical trials. OBJECTIVES: To evaluate safety data from risankizumab psoriasis phase I-III clinical trials. METHODS: Short-term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long-term safety was evaluated using integrated data from 17 phase I-III completed and ongoing trials. RESULTS: Short-term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient-years (PY) of exposure, respectively]. Long-term analyses included 3072 risankizumab-treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure-adjusted adverse event rates did not increase with long-term treatment (318 vs. 171 events per 100 PY for short- and long-term analyses). With long-term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients. CONCLUSIONS: Risankizumab demonstrated a favourable safety profile over short- and long-term treatment in patients with moderate-to-severe psoriasis.

Three-year efficacy and safety of certolizumab pegol for the treatment of plaque psoriasis: results from the randomized phase 3 CIMPACT trial.

BACKGROUND: Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-tumor necrosis factor biologic. OBJECTIVES: To report 3-year outcomes from the CIMPACT (NCT02346240) phase 3, CZP in moderate to severe plaque psoriasis, randomized controlled trial. METHODS: Adults were randomized 3:3:3:1 to CZP 200 mg every other week (Q2W), CZP 400 mg Q2W, etanercept biweekly or placebo. At Week 16, CZP- and etanercept-treated PASI 75 responders were re-randomized to CZP 200 mg Q2W, CZP 400 mg Q4W, CZP 400 mg Q2W or placebo for maintenance treatment; PASI 75 non-responders entered an open-label escape CZP 400 mg Q2W arm. Patients entering the open-label extension (OLE; Weeks 48-144) from blinded treatment received CZP 200 mg Q2W. RESULTS: Double-blinded results have been reported previously. 261 patients received 200 mg Q2W upon OLE entry. PASI 75 response was maintained in patients continuing 200 mg Q2W treatment through Weeks 16-144 (Week 144: 96.2%). In patients dosed down at Week 48 (double-blinded 400 mg to 200 mg Q2W), PASI 75 decreased (Week 48: 98.7%; Week 144: 85.9%). In patients who received placebo through Weeks 16-48, PASI 75 response decreased (Week 48: 60.4%), then increased following Week 48 switch to 200 mg Q2W (Week 144: 95.1%). 48 and 36 patients initially randomized to 200 and 400 mg Q2W, respectively, were Week 16 PASI 75 non-responders and entered the escape arm; at Week 144, 71.8% and 78.2% achieved PASI 75. No new safety signals were identified. CONCLUSIONS: Response to CZP was durable over three years; no new safety signals were identified.

The risk of malignancy in patients with secukinumab-treated psoriasis, psoriatic arthritis and ankylosing spondylitis: analysis of clinical trial and postmarketing surveillance data with up to five years of follow-up.

BACKGROUND: Data on the use of biologic therapy and malignancy risk are inconsistent due to limited long-term robust studies. OBJECTIVES: To assess the malignancy risk in patients with secukinumab-treated psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS). METHODS: This integrated safety analysis from both the secukinumab clinical trial programme and postmarketing safety surveillance data included any patient receiving at least one approved dose of secukinumab with a maximum of 5 years of follow-up. Safety analyses evaluated the rate of malignancy using exposure-adjusted incidence rates [EAIR; incidence rates per 100 patient treatment-years (PTY)]. Standardized incidence ratios (SIRs) were reported using the Surveillance, Epidemiology, and End Results Program (SEER) database as a reference population. Crude incidence of malignancy was also reported using postmarketing surveillance data. RESULTS: Safety data from 49 clinical trials with secukinumab-treated patients were included: 10 685 patients with psoriasis, 2523 with PsA and 1311 with AS. Across indications over a 5-year period, the EAIR of malignancy was 0·85 per 100 PTY [95% confidence interval (CI) 0·74-0·98] in secukinumab-treated patients, corresponding to 204 patients per 23 908 PTY. Overall, the observed vs. expected number of malignancies from secukinumab clinical trial data were comparable, as indicated by an SIR of 0·99 (95% CI 0·82-1·19) across indications. The estimated crude cumulative incidence reporting rate per 100 PTY for malignancy was 0·27 in the postmarketing surveillance data across indications with a cumulative exposure of 285 811 PTY. CONCLUSIONS: In this large safety analysis, the risk of malignancy was low for up to 5 years of secukinumab treatment. These data support the long-term use of secukinumab in these indications.

Addressing challenges associated with long-term topical treatment and benefits of proactive management in patients with psoriasis.

The majority of patients with psoriasis vulgaris (chronic plaque psoriasis) can be treated successfully with short-term topical therapies. However, long-term management of psoriasis with topicals is challenging and tends to take a reactive approach to disease relapse, rather than a proactive approach aimed at maintaining disease remission. Patients are often dissatisfied with the delay in treatment response and inconvenience of applying topical treatments, and therefore frequently discontinue treatment leading to poor outcomes. Relapse is common, particularly with reactive management, as underlying residual disease can remain following initial skin clearance; some patients find that their disease at relapse may be worse than their initial symptoms. This can have a detrimental effect on patient quality of life (QoL) and increase the risk of psoriasis-associated depression. A long-term proactive management approach, with maintenance treatment following initial treatment success, could help sustain disease remission and improve clinical and QoL outcomes for patients. Treatment with fixed-dose calcipotriol 50 µg/g betamethasone dipropionate 0.5 mg/g cutaneous foam (Cal/BD foam) is effective in the short term, providing a fast onset of action and improvements in disease at 4 weeks. Results from the Phase III PSO-LONG study demonstrated that long-term proactive management was superior to reactive management in prolonging time to first relapse, reducing number of relapses and increasing days in remission in adults with psoriasis vulgaris. Furthermore, Cal/BD foam was well tolerated in PSO-LONG. No new safety concerns were identified over 52 weeks; the safety profile was consistent with that described previously. Given this, Cal/BD foam should be considered when prescribing topicals for the long-term proactive management for patients with psoriasis.

Long-term safety of certolizumab pegol in plaque psoriasis: pooled analysis over 3 years from three phase III, randomized, placebo-controlled studies.

BACKGROUND: Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-tumour necrosis factor biologic. OBJECTIVES: To report 3-year safety data from three phase III trials of CZP in adults with plaque psoriasis. METHODS: Data were pooled from CIMPASI-1 (NCT02326298), CIMPASI-2 (NCT02326272) and CIMPACT (NCT02346240). Included patients had moderate-to-severe plaque psoriasis of ≥ 6 months' duration; had been randomized to CZP 200 mg every 2 weeks (Q2W) (400 mg at weeks 0, 2 and 4) or CZP 400 mg Q2W; and had received at least one dose of CZP with up to 144 weeks of exposure. Treatment-emergent adverse events (TEAEs) were classified using MedDRA v18·1. Reported incidence rates (IRs) are incidence of new cases per 100 patient-years (PY). RESULTS: Over 144 weeks, 995 patients received at least one dose of CZP (exposure: 2231·3 PY); 731 and 728 received at least one dose of CZP 200 mg Q2W (1211·4 PY) and/or 400 mg Q2W (1019·9 PY), respectively. The IR [95% confidence interval (CI)] of TEAEs was 144·9 (135·3-155·0) for all patients, 134·1 (123·2-145·7) for CZP 200 mg Q2W and 158·3 (145·5-171·9) for CZP 400 mg Q2W. The IR (95% CI) of serious TEAEs for all patients was 7·5 (6·4-8·8); the IRs were 6·7 (5·2-8·3) and 8·7 (6·9-10·8) for CZP 200 mg and 400 mg Q2W, respectively. Overall, 3·2% of patients reported serious infections (2·2% within each of the CZP 200 and 400 mg Q2W groups). Overall, there was one case of active tuberculosis, 16 malignancies in 14 patients and seven deaths (two considered treatment-related). The cumulative IR of TEAEs did not increase over time. CONCLUSIONS: No new safety signals were identified compared with previously reported data. Risk did not increase with longer or higher CZP exposure.

Safety in moderate-to-severe plaque psoriasis patients with latent tuberculosis treated with guselkumab and anti-tuberculosis treatments concomitantly: results from pooled phase 3 VOYAGE 1 & VOYAGE 2 trials.

BACKGROUND: Patients treated with tumour necrosis factor (TNF) inhibitors are at risk of new-onset tuberculosis (TB) or reactivation of latent tuberculosis infection (LTBI). Association between TB/LTBI and interleukin (IL)-23 inhibitors for psoriasis is unclear. Patients with LTBI typically initiate LTBI therapy before receiving biologics. OBJECTIVES: Safety in moderate-to-severe psoriasis patients with LTBI treated with guselkumab (IL-23 inhibitor) and LTBI treatment was evaluated. METHODS: In the VOYAGE 1 & VOYAGE 2 studies, patients screened for LTBI were randomized to guselkumab, placebo, or adalimumab (TNF inhibitor) at baseline. Placebo â†’ guselkumab crossover occurred at week 16 and adalimumab â†’ guselkumab at week 52 (VOYAGE 1), or at week 28 or later (VOYAGE 2). Incidence of active TB, adverse events (AEs), serious AEs (SAEs), and markedly abnormal liver function tests [alanine aminotransferase test (ALT); aspartate aminotransferase test (AST)] were evaluated using pooled data through week 100 in guselkumab-treated patients receiving and not receiving LTBI treatment. RESULTS: At baseline, 130 randomized patients (guselkumab: n = 69; adalimumab: n = 36; placebo: n = 25) tested positive for LTBI and received concomitant LTBI treatments (LTBI+). No active TB was reported among guselkumab-treated patients without LTBI (LTBI-) through week 100. Two cases of active TB occurred in LTBI- patients treated with adalimumab. Through week 16, across all treatment groups, greater proportions of LTBI+ patients reported ALT and AST elevations compared with LTBI- patients. Through week 100, proportions of patients experiencing AEs and SAEs were comparable between LTBI+ and LTBI- patients. CONCLUSIONS: No cases of active TB, including reactivation of LTBI, were reported in patients with or without LTBI treated with guselkumab through up to 2 years. LTBI treatment was effective across all treatment groups in preventing reactivation of LTBI. Long-term treatment with guselkumab was generally well-tolerated through up to 2 years in patients receiving LTBI medications.

Long-term efficacy and safety of tildrakizumab for moderate-to-severe psoriasis: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2) through 148 weeks.

BACKGROUND: Tildrakizumab is a specific anti-interleukin-23p19 monoclonal antibody approved for the treatment of plaque psoriasis. OBJECTIVES: To evaluate the long-term efficacy and safety of tildrakizumab treatment for patients with moderate-to-severe psoriasis for up to 148 weeks. METHODS: Pooled analysis from two double-blind, randomized controlled trials: reSURFACE 1 and reSURFACE 2. Efficacy was assessed for responders (≥ 75% improvement in Psoriasis Area and Severity Index; PASI 75) and partial responders (PASI 50-75) to tildrakizumab 100 mg and 200 mg at week 28 who were maintained on the same dose (administered every 12 weeks), and for partial responders or nonresponders (PASI < 50) to etanercept 50 mg at week 28 who, after a 4-week washout, were switched to tildrakizumab 200 mg (administered at weeks 32 and 36, and every 12 weeks thereafter). Safety was assessed in the all-patients-as-treated population. Three different methods of imputing missing data were used: nonresponder imputation (NRI), multiple imputation and observed cases. The Clinicaltrials.gov numbers are NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2). RESULTS: At week 148 (NRI), 72·6%, 53·8% and 28·9% of tildrakizumab 100-mg responders and 80·2%, 59·9% and 32·6% of tildrakizumab 200-mg responders had PASI 75, 90 and 100 responses, respectively. For partial responders to tildrakizumab 100 mg and 200 mg, the proportions of patients achieving PASI 75, 90 and 100 responses were 32·5%, 25·0% and 10·0%; and 47·1%, 27·5% and 12·8%, respectively. For patients who were partial responders or nonresponders to etanercept, the proportions of patients achieving PASI 75, 90 and 100 responses were 66·9%, 43·8% and 14·9% at week 148. Rates of discontinuations due to adverse events [tildrakizumab 100 mg: 1·7 per 100 patient-years (PYs); tildrakizumab 200 mg: 1·2 per 100 PYs] and exposure-adjusted rates of serious adverse events (5·9 per 100 PYs; 5·5 per 100 PYs), severe infections (1·1 per 100 PYs; 1·1 per 100 PYs), malignancies (0·6 per 100 PYs; 0·4 per 100 PYs) and major adverse cardiovascular events (0·4 per 100 PYs; 0·5 per 100 PYs) were low. CONCLUSIONS: Tildrakizumab was well tolerated and efficacy was well maintained in week 28 responders who continued tildrakizumab treatment through 3 years, or improved among etanercept partial responders or nonresponders who switched to tildrakizumab. What's already known about this topic? Tildrakizumab 100 mg and 200 mg are efficacious and well tolerated with short-term use in the treatment of patients with moderate-to-severe plaque psoriasis. What does this study add? High levels of efficacy are maintained for up to 3 years of psoriasis treatment with tildrakizumab. There is a favourable long-term safety profile with both tildrakizumab 100 mg and 200 mg, with a low incidence of adverse events of special interest through 3 years.

Utilization of the validated Psoriasis Epidemiology Screening Tool to identify signs and symptoms of psoriatic arthritis among those with psoriasis: a cross-sectional analysis from the US-based Corrona Psoriasis Registry.

BACKGROUND: Despite increasing awareness of the disease, rates of undiagnosed psoriatic arthritis (PsA) are high in patients with psoriasis (PsO). The validated Psoriasis Epidemiology Screening Tool (PEST) is a five-item questionnaire developed to help identify PsA at an early stage. OBJECTIVES: To assess the risk of possible undiagnosed PsA among patients with PsO and characterize patients based on PEST scores. METHODS: This study included all patients enrolled in the Corrona PsO Registry with data on all five PEST questions. Demographics, clinical characteristics and patient-reported outcomes were compared in Corrona PsO Registry patients with PEST scores ≥3 and <3 using t-tests for continuous variables and chi-squared tests for categorical variables; scores ≥3 may indicate PsA. RESULTS: Of 1516 patients with PsO, 904 did not have dermatologist-reported PsA; 112 of these 904 patients (12.4%) scored ≥3 and were significantly older, female, less likely to be working, and had higher BMI than patients with scores <3. They also had significantly longer PsO duration, were more likely to have nail PsO and had worse health status, pain, fatigue, Dermatology Life Quality Index and activity impairment. CONCLUSIONS: Improved PsA screening is needed in patients with PsO because the validated PEST identified over one-tenth of registry patients who were not noted to have PsA as having scores ≥3, who could have had undiagnosed PsA. Appropriate, earlier care is important because these patients were more likely to have nail PsO, worse health-related quality of life and worse activity impairment.

Certolizumab pegol for the treatment of patients with moderate-to-severe chronic plaque psoriasis: pooled analysis of week 16 data from three randomized controlled trials.

BACKGROUND: Certolizumab pegol, an Fc-free, PEGylated, anti-tumour necrosis factor (TNF) biologic, has demonstrated favourable results in three ongoing, phase 3, randomized, double-blinded, placebo-controlled trials in adults with psoriasis. OBJECTIVE: Data were pooled from the ongoing trials to investigate efficacy in selected subgroups and add precision to estimates of treatment effects during the initial 16 weeks of treatment. METHODS: In each trial, patients ≥18 years with moderate-to-severe chronic plaque psoriasis for ≥6 months were randomized to receive certolizumab 400 mg, certolizumab 200 mg or placebo every 2 weeks for 16 weeks. Coprimary endpoints for the pooled analysis were responder rates at Week 16, defined as ≥75% reduction in psoriasis area and severity index (PASI 75) and physician global assessment (PGA) of 0/1 ('clear'/'almost clear' with ≥2-category improvement). Safety was assessed by treatment-emergent adverse events. RESULTS: A total of 850 patients treated with certolizumab 400 mg (N = 342), certolizumab 200 mg (N = 351) or placebo (N = 157) were included in the pooled analysis. At Week 16, PASI 75 and PGA 0/1 responder rates were 80.1% and 63.7% in the certolizumab 400 mg group, 74.5% and 54.6% in the certolizumab 200 mg group, and 7.5% and 2.8% in the placebo group (P < 0.0001 for each dose versus placebo). In patients with and without prior biologic therapy, both doses of certolizumab resulted in substantially higher responder rates versus placebo. The incidence of adverse events was generally similar between the 400 mg and placebo groups, and somewhat lower in the 200 mg group versus placebo. No new safety signals were identified. CONCLUSION: Certolizumab pegol 400 mg or 200 mg every 2 weeks for 16 weeks was associated with statistically significant and clinically meaningful improvements in signs and symptoms of psoriasis in patients with and without prior biologic therapy, and a safety profile consistent with the anti-TNF class in psoriasis.

Physician perspectives in the management of psoriasis and psoriatic arthritis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis survey.

BACKGROUND: Available literature on psoriasis and psoriatic arthritis (PsA) demonstrates a tremendous burden of disease and suggests underdiagnosis and undertreatment. OBJECTIVE: To obtain real-world physician perspectives on the impact of psoriasis and PsA and its treatment on patients' daily lives, including perceptions of, and satisfaction with, current therapies. METHODS: The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) surveyed dermatologists (n = 391) and rheumatologists (n = 390) in North America (Canada and the United States) and Europe (France, Germany, Italy, Spain and United Kingdom). RESULTS: Dermatologists classified 20.3% and 25.7% of their patients as having severe psoriasis and severe PsA respectively; rheumatologists indicated that 48.4% of their PsA patients had active disease. Of the psoriasis patients complaining of joint pain, only 33.0% had a diagnosis of PsA. An impact on daily activities or social/emotional well-being was recognized by 57.2% to 79.3% of physicians. In patients with moderate-to-severe psoriasis, dermatologists reported 74.9% were receiving topical therapy, 19.5% conventional oral therapy and 19.6% biologics. Dermatologists and rheumatologists reported similar rates of topical (≈45%) and biologic (≈30%) therapy utilization for their PsA patients; conventional oral therapy was more often prescribed by rheumatologists (63.4%) vs. dermatologists (35.2%). Reasons for not initiating or maintaining systemic therapies were related to concerns about long-term safety, tolerability, efficacy and costs (biologics). CONCLUSION: Physicians in North America and Europe caring for patients with psoriasis and PsA acknowledge unmet treatment needs, largely concerning long-term safety/tolerability and efficacy of currently available therapies; evidence suggests underdiagnosis of PsA and undertreatment of psoriasis among dermatologists.

Physician perceptions and experience of current treatment in actinic keratosis.

BACKGROUND: Topical therapy is important in the treatment of actinic keratosis (AK), a major risk factor for, and early development stage of, squamous cell carcinoma. Despite this, research addressing the limitations and challenges associated with topical field therapy in actinic keratosis is lacking. OBJECTIVES: The aim of this study was to highlight the challenges associated with maximizing compliance in patients receiving topical AK therapy and to investigate real-world experience with currently available topical therapies including perceptions of adherence and persistence. METHODS: A 45-min online survey was developed and completed by physicians in eight countries. All had previously prescribed topical AK therapy and ≥1 other treatment. Physicians' consensus was summarized as overall agreement/disagreement from ≥70% of respondents (≥60% for case-specific questions). RESULTS: More than 70% of the 427 respondents agreed that topical field therapy is essential and had concerns that lengthy treatments and local skin reactions caused non-adherence/persistence. More than 90% of physicians would preferentially prescribe the shortest duration treatment to such patients. CONCLUSIONS: The research clarifies the challenges associated with prescribing topical AK therapy and highlights that short treatment duration and rapid clearance of skin reactions are key considerations for physicians. This provides a basis for the generation of recommendations for improving the real-world efficacy of topical therapy.

Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up.

BACKGROUND: Long-term safety evaluations of biologics are needed to inform patient management decisions. OBJECTIVES: To evaluate the safety of ustekinumab in patients with moderate-to-severe psoriasis treated for up to 5 years. METHODS: Safety data were pooled from four studies of ustekinumab for psoriasis. Rates of adverse events (AEs), serious AEs (SAEs) and AEs of interest [infections, nonmelanoma skin cancers (NMSCs), other malignancies and major adverse cardiovascular events (MACE)] per 100 patient-years (PY) of follow-up were analysed by ustekinumab dose (45 or 90 mg) and by year of follow-up (years 1-5) to evaluate the dose response and impact of cumulative exposure. Observed rates of overall mortality and other malignancies were compared with those expected in the general U.S. population. RESULTS: Analyses included 3117 patients (8998 PY) who received one or more doses of ustekinumab, with 1482 patients treated for ≥4 years (including 838 patients ≥5 years). At year 5, event rates (45 mg, 90 mg, respectively) for overall AEs (242·6, 225·3), SAEs (7·0, 7·2), serious infections (0·98, 1·19), NMSCs (0·64, 0·44), other malignancies (0·59, 0·61) and MACE (0·56, 0·36) were comparable between dose groups. Year-to-year variability was observed, but no increasing trend was evident. Rates of overall mortality and other malignancies were comparable with those expected in the general U.S. population. CONCLUSIONS: No dose-related or cumulative toxicity was observed with increasing duration of ustekinumab exposure for up to 5 years. Rates of AEs reported in ustekinumab psoriasis trials are generally comparable with those reported for other biologics approved for the treatment of moderate-to-severe psoriasis.

Assessment and management of methotrexate hepatotoxicity in psoriasis patients: report from a consensus conference to evaluate current practice and identify key questions toward optimizing methotrexate use in the clinic.

Experts in psoriasis, hepatology, pharmacokinetics and pharmacogenetics convened to discuss the safety and monitoring of methotrexate with respect to hepatotoxicity when used in the treatment of psoriasis. Methotrexate is an efficacious and cost-effective treatment for psoriasis, but is associated with significant safety issues, particularly relating to hepatotoxicity. Current British, Dutch, German, EU and US guidelines for baseline evaluations, monitoring and prevention of hepatotoxicity in patients with psoriasis receiving methotrexate were evaluated. Liver safety monitoring is currently reliant upon multiple methods, including biopsy, serological tests for biomarkers such as type III procollagen amino terminal propeptide (PIIINP), and liver function tests based on liver enzymes. Monitoring of patients receiving long-term therapy is expected to be improved by the utilization of serum biomarkers currently in development such as the Enhanced Liver Fibrosis (ELF) panel and other non-invasive tests of hepatic architecture, such as fibroelastography, microbubbles and magnetic resonance imaging. Appropriate studies to determine optimal dosing to maximize efficacy and minimize toxicity, potentially utilizing pharmacogenetic principles, are clearly needed. Key questions for future research are identified including needs for optimal screening and monitoring, identification of appropriate biomarkers, assessment of relationships between dosing and safety, utility of liver biopsy, optimal dosing regimens (including route of administration), methods to measure methotrexate levels in blood, and use of methotrexate as a standardized active comparator in trials of experimental drugs used to treat psoriasis.

Actinic keratosis: epidemiology and progression to squamous cell carcinoma.

Actinic keratoses are a common problem in the population, and one of the most common conditions treated by dermatologists. Risk factors for the development of actinic keratosis are those associated with increased sun exposure and increased susceptibility to sun exposure such as low latitude, working outdoors, light skin, and history of sunburn. The role of the immune system is clear from the frequency of actinic keratoses in transplant patients. There is strong evidence that actinic keratoses can progress to squamous cell carcinoma, underscoring the need to identify and treat patients at risk.

Acitretin suppression of squamous cell carcinoma: case report and literature review.

Retinoids have been used for the treatment and suppression of cutaneous malignancies in patients with basal cell nevus syndrome, xeroderma pigmentosum, and in patients with recurrent skin cancers as a result of immunosuppression for renal transplantation. We report a 40-year-old male who began to develop multiple squamous cell carcinomas of the skin after treatment with PUVA for severe psoriasis. The numbers of squamous cell carcinomas increased when acitretin was discontinued and decreased when he was taking the drug at a dose of 25 mg daily. Acitretin should be considered as a maintenance therapy for psoriasis patients developing squamous cell carcinomas as a result of PUVA therapy.

Genital lentigines in a 6-year-old boy with a family history of Cowden's disease: clinical and genetic evidence of the linkage between Bannayan-Riley-Ruvacalba syndrome and Cowden's disease.

BACKGROUND: In 1997, it was reported that a PTEN gene deletion, a common genetic mutation in Cowden's disease (CD), was identified in a patient with Bannayan-Riley-Ruvacalba (BRR), suggesting that the two diseases were allelic. However, the clinical overlap between the two diseases has largely remained unclear. OBJECTIVE: To confirm the genetic and clinical association in a family segregating both CD and BRR. METHODS: Clinical evaluation and genetic analysis using a denaturing gradient gel electrophoresis (DGGE), temporal temperature gradient electrophoresis (TTGE), and DNA sequencing techniques. RESULTS: Our patient presents with typical BRR clinical manifestations, including multiple lentigines on his penis, while his mother presents with typical manifestations of CD, including multiple malignancies. Genetic analyses of leukocytes from the patient and his mother showed mutations in exon 8 that was identified as the presumably truncating mutation R335X. CONCLUSION: This report provides clinical evidence that both BRR and CD are closely related and confirms the PTEN gene mutation in BRR and CD patients segregating in the same family, thus confirming the genetic linkage between the two genodermatoses.

Acne therapy: clinical pearls.

Several classes of medications successfully treat acne. Systemic and topical retinoids, systemic and topical antimicrobials, and systemic hormonal therapy are the major categories. Failure of therapy may result from drug interactions, antibiotic resistance, or coexisting conditions; therefore, a detailed history including these points should be used to decide which therapy is appropriate for each patient. Furthermore, one must consider the potential side effects of each treatment and make sure that (1) the benefits outweigh the risks of the treatment, (2) the side effects can be avoided by adding another agent, or (3) the side effects can be safely treated.

Treatment of psoriasis. Part 1. Topical therapy and phototherapy.

UNLABELLED: New developments in the topical therapy and phototherapy of psoriasis have greatly improved our ability to safely and effectively treat this debilitating disease. Topical corticosteroids remain the most commonly prescribed agents for psoriasis, but they are frequently prescribed with other agents. Investigations of corticosteroids claiming an improved benefit/risk ratio have yielded promising results, but more work is needed. Use of anthralin and tar has declined with the availability of the noncorticosteroids calcipotriene and tazarotene. Other experimental topical therapies are in various stages of development. Broadband ultraviolet B (UVB) remains the most commonly used phototherapy light source, but many patients are being treated with a new form of ultraviolet light, narrowband UVB. Although PUVA remains one of the most effective psoriasis treatments, its use is declining because of its association with cutaneous malignancies. New radiation sources such as lasers have been added to our armamentarium of available therapies and even newer light source-based treatments are being examined. LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be familiar with the varying topical treatments for psoriasis as well as the different modalities of phototherapy. Participants should also have a better understanding of side effects associated with each treatment, which should help in determining options for therapy.