Publications by authors named "Carle Paul"

135 Publications

Use of Complementary and Alternative Medicines by Patients with Psoriasis: Results from a Study with 2562 Patients.

Am J Clin Dermatol 2021 Feb 21. Epub 2021 Feb 21.

Department of Dermatology, Timone Hospital, University Hospital of Marseille, Marseille, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40257-021-00587-7DOI Listing
February 2021

European Task Force on Atopic Dermatitis (ETFAD): position on vaccination of adult patients with atopic dermatitis against COVID-19 (SARS-CoV-2) being treated with systemic medication and biologics.

J Eur Acad Dermatol Venereol 2021 Feb 15. Epub 2021 Feb 15.

Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.

The coronavirus disease 2019 (COVID-19) pandemic is caused by rapid spread of different strains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The severity of infection ranges from mild, or even asymptomatic, to very severe. Signs and symptoms include fatigue, fever, exanthemas, upper respiratory illness, loss of smell and taste, pneumonia, severe acute respiratory syndrome, and multi-organ failure. Risk factors for a severe or lethal course include age, male gender, obesity, diabetes, cardiovascular disease, and immune suppression .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jdv.17167DOI Listing
February 2021

First-Line Biologic Therapy and Obesity in Moderate-to-Severe Psoriasis: Results from the Prospective Multicenter Cohort Psobioteq.

Dermatology 2021 Feb 3:1-9. Epub 2021 Feb 3.

Department of Dermatology, Hôpital Henri Mondor, Créteil, France,

Background: Obesity is associated with an increased risk of psoriasis.

Objective: In this study, we examined whether body mass index (BMI) is taken into account when choosing first-line biologic therapy for psoriasis.

Methods: In this cohort study, we compared obese (BMI ≥30 kg/m2) and non-obese patients for the first-line biologic therapy prescribed, its survival, reasons for discontinuation, therapy optimization, co-prescription of methotrexate and factors associated with long drug survival.

Results: A total of 931 patients were included: 594 (64%) were male, median age was 46 years (interquartile range 36-56). The most-prescribed biologic agents as first-line treatment were adalimumab (ADA; 42.7%), ustekinumab (UST; 29.9%) and etanercept (ETA; 22.9%); only frequency of infliximab (IFX) prescription differed between groups. Drug survival was significantly shorter for obese than non-obese patients (p < 2.10-4) and was worse for obese than non-obese patients for UST (p = 0.009) and ETA (p = 0.02), with no difference for ADA (p = 0.11). The main reason for discontinuation was primary inefficacy (62%), which was more frequent in obese than non-obese patients. The cumulative incidence of optimization did not significantly differ between the groups, except for ADA (SHR 1.91, 95% CI [1.23-2.96], p = 0.005). On multivariate analysis, risk of discontinuation was associated with only ETA as first-line biologic therapy (HR 1.51, 95% CI 1.04-2.19).

Conclusion: This study highlighted the lack of difference in prescription of first-line biologic treatment, except for IFX, between obese and non-obese patients presenting moderate-to-severe psoriasis. Drug survival in obese patients is shorter, mainly because of inefficacy, than in non-obese patients. This highlights the need for targeted pharmacological studies in obese individuals to find optimal administration schemes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000513398DOI Listing
February 2021

How to assess patient satisfaction regarding physician interaction: A systematic review.

Dermatol Ther 2020 Dec 24:e14702. Epub 2020 Dec 24.

Dermatology Department, Hôpital Larrey-CHU (University Hospital Centre), Université Paul Sabatier, Toulouse, France.

Patient satisfaction is an important health care quality indicator. This is particularly relevant in chronic diseases, such as, many dermatological diseases. The purpose of the current systematic review was to assess the validated tools measuring patient satisfaction with physician interaction. We performed a systematic review search in Pubmed, Cochrane Library, and EMBASE. The psychometric properties of the instruments and the domains explored were assessed. Overall, 2229 articles were extracted from the literature search. Of these, 146 articles were eligible for inclusion, 55 were included, and 22 scores were selected. A total of 13 instruments reported cross-cultural validation and the EUROPEP score highlighted the most diverse cross-cultural validation involving 11 different countries. All scores were assessed for content validity, construct validity, factor analysis, reliability, and responsiveness to change. The extent of the validation varied between scores with a few assessing practicability. The following domains were explored: listening skills, empathy, caring/compassion, confidentiality, honesty, behavior, competency/technical skills, satisfaction with the information provided, time given, availability, the environment, trust in the physician, ability to comply with the recommendations, and readiness to recommend the physician to other patients. We identified a total of 22 validated instruments. The major gaps in the validation process appear to be the practicability of the scores and the cross-cultural validation. Major domains evaluated by the scores are communication skills that can be improved by specific training. There is a need to improve evaluation of the quality of the patient-physician relationship in dermatology using validated instruments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dth.14702DOI Listing
December 2020

Long-term efficacy and safety of ixekizumab: A 5-year analysis of the UNCOVER-3 randomized controlled trial.

J Am Acad Dermatol 2020 Nov 28. Epub 2020 Nov 28.

Toulouse University and Larrey Hospital, Toulouse, France.

Objective: To report the efficacy and safety of the approved ixekizumab (IXE) dose over 5 years from UNCOVER-3 (NCT01646177).

Methods: Patients (N = 1346) were randomized 1:2:2:2 to receive subcutaneous injections of placebo, etanercept 50 mg twice weekly, or IXE 80 mg every 2 weeks or every 4 weeks after an initial dose of IXE 160 mg, respectively. At week 12, patients entered the long-term extension period with dosing of IXE every 4 weeks and could escalate to every 2 weeks after week 60. Efficacy was reported for the IXE every 2 weeks/every 4 weeks group of the intent-to-treat population. Safety was reported for patients who received at least 1 dose of IXE every 2 or every 4 weeks.

Results: Using modified nonresponder imputation, 78.8%/67.1%/46.2% of patients receiving the approved dose of IXE every 2 weeks/every 4 weeks (n = 385) achieved ≥75%, ≥90%, or 100% improvement from baseline in the Psoriasis Area and Severity Index, respectively, at week 264; static Physician's Global Assessment score of 0/1 and 0 responses were 69.2% and 45.3%, respectively. Infections were the most observed treatment-emergent adverse event (72.7% of patients).

Limitations: Lack of comparison treatment group after week 12.

Conclusion: IXE demonstrates sustained efficacy and consistent safety through 264 weeks in patients using the approved dose.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2020.11.022DOI Listing
November 2020

Unmet medical needs in the treatment of atopic dermatitis in infants: An Expert consensus on safety and efficacy of pimecrolimus.

Pediatr Allergy Immunol 2020 Nov 29. Epub 2020 Nov 29.

Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.

Atopic dermatitis (AD) is a common skin disease during infancy, which imposes a considerable burden on patients, their families, and the society, requiring effective treatment options that result in rapid and sustained symptom relief. Additionally, early treatment may prevent the development of atopic comorbidities by restoring the skin barrier. Currently, topical standard-of-care for AD in infants includes emollients and topical corticosteroids (TCS) to treat and reduce the risk of flares. However, only few have been approved for infants and long-term maintenance therapy with TCS is not indicated due to potential local and systemic side effects, including skin atrophy. Accordingly, the recently updated European guidelines for treatment of AD recommend topical calcineurin inhibitors (TCIs) for long-term use, treatment of sensitive skin areas, and for use in the pediatric population. Evidence on the use of TCIs for infants has almost been exclusively collected for pimecrolimus, with >4000 infants evaluated in clinical trials, consistently confirming that pimecrolimus is a safe and effective treatment for infants with AD. Nevertheless, its use is still restricted in most countries to children above the age of 2 years due to initial and mostly theoretical safety concerns. Based on a careful review of the available evidence of clinical trials, post-marketing surveillance, and epidemiological studies, an Expert Panel of European dermatologists and pediatric allergologists concluded that these safety concerns are no longer valid. Therefore, pimecrolimus offers a safe and effective alternative to TCS in infants aged 3 months and above, and labeling restrictions in this age group are no longer justified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pai.13422DOI Listing
November 2020

Psoriasis, conception et grossesse : attentes et perspectives.

Authors:
Carle Paul

Eur J Dermatol 2020 Oct;30(S1)

Service de dermatologie; Pôle voies respiratoires; CHU de Toulouse, hôpital Larrey; Toulouse.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/ejd.2020.3888DOI Listing
October 2020

Impact of Atopic Dermatitis Lesion Location on Quality of Life in Adult Patients in a Real-world Study.

J Drugs Dermatol 2020 10;19(10):943-948

Background: Atopic dermatitis (AD) has a negative impact on patients’ quality of life (QoL).

Objective: To report the impact of specific AD lesion locations on QoL in adult patients with AD using real-world data.

Methods: The Adelphi US Disease Specific Programme was conducted between January–April 2018. Physicians documented patient demographics/characteristics, AD lesion locations, and body surface area; patients completed questionnaires reporting the impact of lesion locations on QoL.

Results: AD severity was moderate in 51.6% of patients and severe in 6.0%. Lesions were commonly identified in more than one location. All AD lesion locations impacted QoL. Visible areas were most bothersome, including head/neck (68%), hands/fingers (58%), front (30%), upper extremities (22%), and lower extremities (16%), with statistically significant associations for a number of Dermatology Life Quality Index (DLQI) items. Itch, soreness, pain, and stinging are also associated with a number of body areas but in particular with those that are most visible/accessible. Lesions on the head/neck and hands/fingers (58%) demonstrated an increased impact on the anxiety and depression dimension of the EuroQol 5-Dimension tool.

Conclusions: In patients with AD, quality of life was most affected in patients with lesions in visible areas, including head/neck, hands/fingers, and upper extremities, with statistically significant associations for a number of DLQI domains. Physicians should be aware of the burden of AD lesions on QoL and consider having conversations with patients to better understand the impact of these lesions. Prior presentation: 28th Annual European Academy of Dermatology and Venereology Congress; 9–13 October 2019, Madrid, Spain. Poster number P0233.J Drugs Dermatol. 2020;19(10): 943-948. doi:10.36849/JDD.2020.5422.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.36849/JDD.2020.5422DOI Listing
October 2020

Association Between Patient- and Physician-Reported Outcomes in Patients with Moderate-To-Severe Plaque Psoriasis Treated with Biologics in Real Life (PSO-BIO-REAL).

Dermatol Ther (Heidelb) 2020 Oct 6;10(5):1099-1109. Epub 2020 Aug 6.

Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.

Introduction: Clinical trials have shown that psoriasis patients who achieve complete skin clearance are more likely to report no impairment in health-related quality of life (HRQoL) and no psoriasis symptoms versus patients who achieve almost complete skin clearance. However, real-world data are lacking. The objective of this study was to estimate the real-world proportion of moderate-to-severe psoriasis patients on biologic treatment who achieved a Psoriasis Symptom Inventory (PSI) total score of 0 (PSI 0; no symptoms) and a Dermatology Life Quality Index (DLQI) score of 0/1 (DLQI 0/1; no impact on HRQoL), and to study the relationship between patient-reported symptoms and HRQoL versus physician-reported psoriasis severity (Psoriasis Area and Severity Index [PASI]).

Methods: The PSO-BIO-REAL study was a multinational, prospective, real-world, non-interventional study that included patients aged ≥ 18 years with moderate-to-severe plaque psoriasis who had initiated biologic therapy (either biologic-naïve or had switched biologics [biologic-experienced]). Psoriasis symptoms were evaluated using the PSI, and HRQoL was assessed using the DLQI. Assessments were conducted at baseline and at 6 and 12 months after initiating biologic treatment. Associations between PSI and DLQI with PASI were evaluated using Spearman correlation coefficients. Post-hoc analyses evaluated individual PSI items and the association to PASI response, DLQI and PSI by index biologic.

Results: At 12 months, 25.5% of patients achieved PSI 0, and 51.2% achieved DLQI 0/1, with greater proportions achieving these scores among biologic-naïve than among biologic-experienced patients. There was a moderate-to-strong correlation between PSI and DLQI scores and PASI scores, with 64.8% of patients with absolute PASI 0 and 19.4% with absolute PASI > 0 ≤ 2 achieving PSI 0 (6 and 12 months pooled). Achievement of response varied by index biologic.

Conclusion: This study demonstrates that in a real-world setting patients' QoL improves with skin clearance. The results also demonstrate that the correlation between skin clearance and improvements in HRQoL (DLQI) and psoriasis symptoms (PSI) is not complete, which highlights the importance of considering both patient- and physician-reported outcomes in the assessment of psoriasis treatment outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13555-020-00428-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477065PMC
October 2020

Integrated multidisciplinary approach to hidradenitis suppurativa in clinical practice,.

Int J Womens Dermatol 2020 Jun 22;6(3):164-168. Epub 2020 Feb 22.

Department of Dermatology, Paul Sabatier University and Larrey Hospital, Toulouse, France.

Background: The European hidradenitis suppurativa (HS) guidelines recommend a multidisciplinary approach for patients with HS and management of comorbidities.

Objective: We aimed to describe the organization of a multidisciplinary HS program and characterize the patient population.

Methods: We conducted a retrospective study of patients with HS undergoing prospectively defined multidisciplinary work-up including examinations by a dermatologist, plastic surgeon, smoking specialist, and nutritionist in our outpatient unit between October 2015 and January 2017.

Results: The study included 49 patients with a sex ratio of 1:1. A total of 73.4% of patients were smokers, 20.4% were overweight, 48.9% were obese, and 30.6% had symptoms of depression. The mean Sartorius score was 30.4 (±17.6). The outcome of plastic surgery consultation was as follows: 16 patients had operations, 5 were excluded based on medical history, 9 refused surgery, and 16 remained undecided. The refusal rates for consulting with the smoking cessation and nutrition specialists were 55.8% and 69.5%, respectively. Twelve patients received antibiotics, 9 received biologics, 9 underwent medico-surgical treatment, 9 underwent surgery, and 10 were lost to follow-up. The mean visual analogue scale score for satisfaction was 8.3 (±1.6; n = 28).

Conclusion: An integrated multidisciplinary care model for HS is associated with high patient satisfaction. Adherence to the proposed comorbidity management was higher in female patients and related to empathetic interactions with physicians.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijwd.2020.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330447PMC
June 2020

The Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): The development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis.

J Am Acad Dermatol 2020 Sep 25;83(3):839-846. Epub 2020 Apr 25.

The George Washington University School of Medicine and Health Sciences, Washington, DC.

Background: An Investigator Global Assessment (IGA) is recommended by health agencies for drug registration in atopic dermatitis (AD). Current IGA scales lack standardization.

Objectives: To develop an IGA scale, training module, and clinical certification examination for use in AD trials; establish content validity; and assess reliability.

Methods: Expert dermatologists participated in the development of the validated IGA for AD (vIGA-AD). Reliability (interrater and intrarater) was assessed by 2 web-based surveys. Clinical certification for investigators consisted of a training module and examination.

Results: Expert consensus was achieved around a 5-point IGA scale including morphologic descriptions, and content validity was established. Survey 1 showed strong interrater reliability (Kendall's coefficient of concordance W [Kendall's W], 0.809; intraclass correlation [ICC], 0.817) and excellent agreement (weighted kappa, 0.857). Survey 2, completed 5 months after training of dermatologists, showed improvements in scale reliability (Kendall's W, 0.819; ICC, 0.852; weighted kappa, 0.889). In this study, 627 investigators completed vIGA-AD training and certification.

Limitations: Ratings were assessed on photographs.

Conclusion: A validated IGA scale and training module were developed with the intent of harmonizing assessment of disease severity in AD trials. Strong reliability and excellent agreement between assessments were observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2020.04.104DOI Listing
September 2020

532 nm Q-switched laser for the treatment of hyperpigmentation induced by topical tacrolimus.

J Cosmet Laser Ther 2020 Feb 21;22(2):90-92. Epub 2020 Mar 21.

Department of Dermatology, Paul Sabatier University, Toulouse University Hospital, Toulouse, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14764172.2020.1740273DOI Listing
February 2020

Omalizumab in the treatment of adult patients with mastocytosis: A systematic review.

Clin Exp Allergy 2020 06 25;50(6):654-661. Epub 2020 Mar 25.

Department of Dermatology, Mastocytosis National Reference Center (CEREMAST), Toulouse University Hospital, Toulouse, France.

BACKGROUND: Mastocytosis is associated with mast cell (MC) mediator-related symptoms for which limited therapies are available. OBJECTIVE: Our aim was to assess the efficacy and safety of omalizumab in the treatment of MC mediator-related symptoms in adult patients with mastocytosis. RESULTS: We identified one multi-centre retrospective cohort study (39 patients), one retrospective cohort study (13 patients), 4 case series and 10 case reports. No published controlled randomized study was identified. We included 69 patients (13 patients with cutaneous mastocytosis and 56 with systemic mastocytosis). The mean age was 48 years. Omalizumab maintenance dose was 300 mg for the majority of patients. The mean duration of treatment was 17 months. Treatment led to a tolerability of venom immunotherapy and to a complete resolution of severe reactions in all patients with post-honeybee sting anaphylaxis. Complete resolution of idiopathic anaphylaxis episodes was noted in 84% of the patients. Complete resolution of palpitations, gastrointestinal, cutaneous, neuropsychiatric, respiratory and musculoskeletal symptoms was observed at a rate of 43%, 29%, 27%, 11%, 9% and 0%, respectively. Efficacy was maintained for the entire duration of the treatment in all but four responders. Adverse events were reported for 13 patients. CONCLUSIONS AND CLINICAL RELEVANCE: Omalizumab appears to prevent some life-threatening reactions associated with mastocytosis and may be a good option to treat the associated symptoms. However, the evidence relied upon is observational, uncontrolled and from a small number of patients. A randomized controlled trial is needed to better understand the place of omalizumab in mastocytosis treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cea.13592DOI Listing
June 2020

Trial of Nemolizumab in Moderate-to-Severe Prurigo Nodularis.

N Engl J Med 2020 02;382(8):706-716

From the Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Münster (S.S.), the Department of Dermatology and Allergy, Christine Kühne Center for Allergy Research and Education, University Hospital, Bonn (T.B.), and the Department of Dermatology and Allergy, Ludwig Maximilian University of Munich, Munich (A.W.) - all in Germany; the Itch Center, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Hospital, Miami (G.Y.); the Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria (F.J.L.); the Department of Dermatology, University Hospital of Nice, Nice (J.-P.L.), the Department of Dermatology, University of Toulouse, Toulouse (C. Paul), and the Department of Dermatology, University Hospital of Brest, Brest (L.M.) - all in France; the Department of Dermatology, Medical University of Lodz, Lodz (J.N.), and the Department of Dermatology, University of Rzeszow, Rzeszow (A.R.) - both in Poland; Galderma, Fort Worth, TX (F.A.); and Galderma, Lausanne, Switzerland (C. Piketty).

Background: Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis.

Methods: We conducted a 12-week, randomized, double-blind, phase 2 trial of nemolizumab (at a dose of 0.5 mg per kilogram of body weight) administered subcutaneously at baseline, week 4, and week 8, as compared with placebo, in patients with moderate-to-severe prurigo nodularis and severe pruritus. Moderate-to-severe prurigo nodularis was defined as 20 or more nodules, and severe pruritus was defined as a mean score of at least 7 for the worst daily intensity of pruritus on the numerical rating scale (scores range from 0 [no itch] to 10 [worst itch imaginable]). The primary outcome was the percent change from baseline in the mean peak score for pruritus on the numerical rating scale at week 4. Secondary outcomes included additional measures of itching and disease severity. Safety assessments were performed through week 18.

Results: A total of 70 patients were randomly assigned in a 1:1 ratio to receive nemolizumab (34 patients) or placebo (36). The initial pruritus score on the numerical rating scale was 8.4 in each group. At week 4, the peak pruritus score on the numerical rating scale was reduced from baseline by 4.5 points (change, -53.0%) in the nemolizumab group, as compared with a reduction of 1.7 points (change, -20.2%) in the placebo group (difference, -32.8 percentage points; 95% confidence interval, -46.8 to -18.8; P<0.001). Results for secondary outcomes were in the same direction as for the primary outcome. Nemolizumab was associated with gastrointestinal symptoms (abdominal pain and diarrhea) and musculoskeletal symptoms.

Conclusions: Nemolizumab resulted in a greater reduction in pruritus and severity of skin lesions than placebo in patients with prurigo nodularis but was associated with adverse events. Larger and longer trials are needed to determine the durability and safety of nemolizumab for the treatment of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT03181503.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa1908316DOI Listing
February 2020

Safety of Ixekizumab Treatment for up to 5 Years in Adult Patients with Moderate-to-Severe Psoriasis: Results from Greater Than 17,000 Patient-Years of Exposure.

Dermatol Ther (Heidelb) 2020 Feb 20;10(1):133-150. Epub 2019 Nov 20.

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Introduction: Long-term safety data are critical for evaluating therapies for psoriasis. Ixekizumab has demonstrated efficacy and is well tolerated for the treatment of moderate-to-severe plaque psoriasis. We examined the safety and tolerability of up to 5 years of ixekizumab therapy in patients with psoriasis.

Methods: Integrated safety data were analyzed from 13 ixekizumab clinical studies. Rates of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest were analyzed for the 12-week induction period in the combined pivotal studies, and for all pooled studies by year(s) of therapy and overall, reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (p-y) and/or frequencies.

Results: Total ixekizumab exposure was 17,003.4 p-y (N = 5898); 2749 patients had ≥ 4 years of exposure. When compared across years of exposure, rates for AEs remained largely stable or declined, including TEAEs leading to discontinuation (3.8/100 p-y in year 1, declining to 2.0/100 p-y in year 5); SAEs (range 6.2-7.0/100 p-y); serious infections (range 1.3-1.7/100 p-y); nonmelanoma skin cancer (ranging from 0.5/100 p-y in year 1 to 0.2/100 p-y in years 4-5); other malignancies (range 0.4-0.6/100 p-y); inflammatory bowel disease including ulcerative colitis and Crohn's disease (IR 0.2/100 p-y); and major adverse cardiovascular events (MACE) (range 0.3-0.7/100 p-y). Candidiasis was reported in 327 patients (IR 1.9/100 p-y), with the majority identified as mucocutaneous. The rate of injection site reactions was 15.5/100 p-y during year 1 and 2.0-2.3/100 p-y by years 3-5.

Conclusions: The decrease in rates of TEAEs and the stable rates of SAEs, other malignancies and MACE during up to 5 years of ixekizumab dosing are consistent with previous reports describing a favorable safety profile of ixekizumab following shorter durations of exposure.

Funding: Eli Lilly and Company.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13555-019-00340-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994584PMC
February 2020

Ixekizumab treatment and the impact on SF-36: results from three pivotal phase III randomised controlled trials in patients with moderate-to-severe plaque psoriasis.

Qual Life Res 2020 Feb 26;29(2):369-380. Epub 2019 Oct 26.

Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg, Hamburg, Germany.

Purpose: To assess improvements in health-related quality of life (HRQoL) with ixekizumab treatment in patients with moderate-to-severe psoriasis.

Methods: Adults with plaque psoriasis were enrolled in phase III, double-blind, randomised, controlled trials (UNCOVER-1, UNCOVER-2, or UNCOVER-3). All 3 protocols included a 12-week, placebo-controlled induction period; UNCOVER-2 and UNCOVER-3 also had an active-control group (50 mg etanercept) during induction. After induction, patients in UNCOVER-1 and UNCOVER-2 entered a 48-week withdrawal (maintenance) period (Weeks 12-60), during which Week-12 sPGA (0,1) responders were rerandomized to receive placebo, or 80 mg ixekizumab every 4 weeks (Q4W) or 12 weeks. As a secondary objective, HRQoL was measured by the generic Medical Outcomes Survey Short Form-36 (SF-36) at baseline and Weeks 12 and 60. Changes in mean SF-36 Physical and Mental Component Summary (PCS and MCS) and domain scores and proportions of patients reporting improvements ≥ minimal important differences in SF-36 scores were compared between groups.

Results: At Week 12, ixekizumab-treated patients (both dose groups in UNCOVER-1, -2, and -3) reported statistically significantly greater improvements in mean SF-36 PCS and MCS and all 8 SF-36 domain scores versus placebo. Further, more ixekizumab-treated patients than placebo-treated patients reported at least minimal treatment responses in SF-36 PCS and MCS scores and domain scores. Overall improvements in SF-36 PCS and MCS scores were maintained through Week 60.

Conclusions: Ixekizumab-treated patients reported statistically significant improvements in HRQoL at 12 weeks that persisted through 1 year.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11136-019-02296-5DOI Listing
February 2020

Early necrotic skin lesions after a ABO-incompatible kidney transplantation: The threat of Cunninghamella Spp.

Transpl Infect Dis 2019 Dec 21;21(6):e13173. Epub 2019 Oct 21.

Department of Nephrology, Dialysis and Organ Transplantation, Toulouse University Hospital, Toulouse, France.

A 49-year-old man underwent ABO-incompatible kidney transplantation with a living donor. At day 33 post-transplantation, he presented with undiagnosed epilepsy with generalized tonic-clonic seizures. At day 44 post-transplantation, he developed left-sided pneumonia attributed to Aspergillus fumigatus and treatment with liposomal amphotericin B was initiated. At day 51 post-transplantation, necrotic skin lesions appeared. DNA sequencing in a fresh cutaneous biopsy finally identified Cunninghamella Spp., a member of the order Mucorales. Unfortunately, the necrotic lesions spread, and the patient died at day 60 post-transplantation. This case report highlights the infectious risk related to ABO-incompatible kidney transplantation and suggests a requirement for rapid identification of every skin lesion, even in the early phases of immunosuppression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tid.13173DOI Listing
December 2019

Positive change in hand care habits using therapeutic patient education in chronic hand eczema.

Contact Dermatitis 2020 Jan 7;82(1):10-17. Epub 2019 Oct 7.

Dermatology and Allergology Department, Larrey Hospital, Toulouse University, Toulouse, France.

Background: Chronic hand eczema (CHE) is a major burden for patients. Maintenance treatment involves prevention measures limiting detrimental behaviour and aggravating factors.

Objective: To evaluate the effect of a standardised care program including therapeutic patient education (TPE) on hand care behaviours, clinical severity, quality of life, and work productivity.

Methods: A single-centre study was conducted prospectively. Together with the prescription of a topical steroid, patients participated in individual TPE sessions. Evaluations were performed initially and repeated three months after the therapeutic intervention. They included a structured analysis of hand care behaviours, the assessment of the mTLSS (modified Total Lesion Symptom Score), DLQI (Dermatology Life Quality Index), and WPAI (Work Productivity and Activity Impairment).

Results: Seventy-one patients were included (30 men, 42.3%). Three months after completion of the standardised care program, hand care behaviours such as hand washing and rinsing, hand drying, wearing protective gloves, using moisturizing creams, and following specific treatments and recommendations for CHE improved significantly in the 58 patients who completed the study and were associated with a significant improvement in the mTLSS, DLQI, and WPAI scores.

Conclusions: TPE helps patients change their hand care behaviours and adopt skin protection measures, and may improve CHE severity, quality of life, and work productivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cod.13390DOI Listing
January 2020

Advanced Cutaneous Squamous Cell Carcinoma Is Associated with Suboptimal Initial Management in a Cohort of 109 Patients.

Dermatology 2019 6;235(6):516-521. Epub 2019 Aug 6.

Dermatology Department, Paul Sabatier Toulouse III University, IUC and CHU de Toulouse, Toulouse, France,

Background: Little is known about the epidemiological characteristics of patients with advanced cutaneous squamous cell carcinoma (A-cSCC).

Objective And Method: A retrospective study was conducted on a routine care cohort of 109 patients to identify the epidemiological factors associated with A-cSCC.

Results: The median age was 83 years (IQR: 73.9-89.8), and the median ECOG was 1 (IQR: 1-2). Sixty percent of the patients had a history of cardiac disease and 22% had cognitive disorders. Seventy-four percent of patients were from rural/semi-rural areas (towns of <15,000 residents) and 17% were living in nursing homes. The cSCC lesions were on the head and neck in 72% of cases. Thirty-seven percent of patients were not diagnosed until the disease was in an advanced stage, indicating a lack of cSCC identification. In the remaining 69 patients, 7% did not received treatment within 3 months of the cSCC being identified, 62% had an incomplete histological report, and 37% had incomplete treatment.

Conclusion: A-cSCC is associated with incomplete initial treatment in an elderly and rural population with good general condition. We hypothesize that a lack of access to good dermatological expertise may have led to underestimation of the aggressiveness of cSCC and/or therapeutic mismanagement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000500636DOI Listing
April 2020

Therapeutische Patientenschulungsprogramme und Unterstützung beim Selbstmanagement für Patienten mit Psoriasis - eine systematische Übersicht.

J Dtsch Dermatol Ges 2019 Jul;17(7):685-697

Division of Evidence-Based Medicine, Department of Dermatology, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ddg.13840_gDOI Listing
July 2019

Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial.

Lancet 2019 08 4;394(10198):576-586. Epub 2019 Jul 4.

Paul Sabatier University and Larrey Hospital, Toulouse, France.

Background: Psoriasis is an autoimmune disease that affects approximately 100 million people worldwide, and is a disease that can be ameliorated by anti-cytokine treatment. We aimed to compare the efficacy and safety of risankizumab with adalimumab in patients with moderate-to-severe plaque psoriasis.

Methods: IMMvent was a phase 3, randomised, double-blind, active-comparator-controlled trial completed at 66 clinics in 11 countries. Eligible patients were aged 18 years or older with moderate-to-severe chronic plaque psoriasis. Patients were randomly assigned 1:1 using interactive response technology to receive 150 mg risankizumab subcutaneously at weeks 0 and 4 or 80 mg adalimumab subcutaneously at randomisation, then 40 mg at weeks 1, 3, 5, and every other week thereafter during a 16-week double-blind treatment period (part A). For weeks 16-44 (part B), adalimumab intermediate responders were re-randomised 1:1 to continue 40 mg adalimumab or switch to 150 mg risankizumab. In part A, participants and investigators were masked to study treatment. Randomisation was stratified by weight and previous tumour necrosis factor inhibitor exposure. Co-primary endpoints in part A were a 90% improvement from baseline (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16, and for part B was PASI 90 at week 44 (non-responder imputation). Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the safety population (all patients who received at least one dose of study drug or placebo). This study is registered with ClinicalTrials.gov, number NCT02694523.

Findings: Between March 31, 2016, and Aug 24, 2017, 605 patients were randomly assigned to receive either risankizumab (n=301, 50%) or adalimumab (n=304, 50%). 294 (98%) of patients in the risankizumab group and 291 (96%) in the adalimumab group completed part A, and 51 (96%) of 53 patients re-randomised to risankizumab and 51 (91%) of 56 patients re-randomised to continue adalimumab completed part B. At week 16, PASI 90 was achieved in 218 (72%) of 301 patients given risankizumab and 144 (47%) of 304 patients given adalimumab (adjusted absolute difference 24·9% [95% CI 17·5-32·4]; p<0·0001), and sPGA scores of 0 or 1 were achieved in 252 (84%) patients given risankizumab and 252 (60%) patients given adalimumab (adjusted absolute difference 23·3% [16·6-30·1]; p<0·0001). In part B, among adalimumab intermediate responders, PASI 90 was achieved by 35 (66%) of 53 patients switched to risankizumab and 12 (21%) of 56 patients continuing adalimumab (adjusted absolute difference 45·0% [28·9-61·1]; p<0·0001) at week 44. Adverse events were reported in 168 (56%) of 301 patients given risankizumab and 179 (57%) of 304 patients given adalimumab in part A, and among adalimumab intermediate responders, adverse events were reported in 40 (75%) of 53 patients who switched to risankizumab and 37 (66%) of 56 patients who continued adalimumab in part B.

Interpretation: Risankizumab showed significantly greater efficacy than adalimumab in providing skin clearance in patients with moderate-to-severe plaque psoriasis. No additional safety concerns were identified for patients who switched from adalimumab to risankizumab. Treatment with risankizumab provides flexibility in the long-term treatment of psoriasis.

Funding: AbbVie and Boehringer Ingelheim.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(19)30952-3DOI Listing
August 2019

[Ciclosporin].

Authors:
Carle Paul

Ann Dermatol Venereol 2019 Jun - Jul;146(6-7):466-469. Epub 2019 Jun 14.

Université Paul-Sabatier et dermatologie, hôpital Larrey, 24, chemin de Pouvourville, 31059 Toulouse, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.annder.2019.04.011DOI Listing
January 2020

Highlights from the 5th World Rendezvous on Dermatology in Rio de Janeiro on 2nd and 3rd November 2018, under the aegis of the Fondation Bioderma.

Authors:
Carle Paul

Eur J Dermatol 2019 Apr;29(S1)

Dermatology, hôpital Larrey, Toulouse University, 31059 Toulouse, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/ejd.2019.3537DOI Listing
April 2019

Therapeutic patient education and self-management support for patients with psoriasis - a systematic review.

J Dtsch Dermatol Ges 2019 Jul 23;17(7):685-695. Epub 2019 Apr 23.

Division of Evidence-Based Medicine, Department of Dermatology, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Psoriasis is a chronic inflammatory skin condition. Patient education may be one option to improve adherence and coping. The aim of this systematic review is to identify studies evaluating educational interventions for psoriasis patients. The review was conducted following the methods recommended by Cochrane. We searched seven databases, one trial register and three grey literature repositories. Data screening and extraction was performed independently by two reviewers. Cochrane Risk of Bias 2.0, ROBINS-I, and NIH tools were used. Additionally, the APEASE criteria were applied. We evaluated 16 studies. Two randomized clinical trials (RCTs) evaluated patient-practitioner or patient-nurse one-to-one interventions, one RCT assessed a web-based intervention and three RCTs reported group interventions taking place frequently; one RCT reported one-off group sessions. The remaining RCT compared the healthcare professionals involved. The risk of bias rating ranged from "some concerns" to "high". Three RCTs found an effect. We included four controlled clinical trials (CCTs), one of which had an effect. One of the four before-and-after-studies warrants further investigation. Despite similarities in delivery mode across the interventions, patients who were eligible and settings in which interventions were delivered differed. Interventions that included an individual (one-to-one) session appeared to be successful. Two interventions seem suitable for adaptation using APEASE: the topical treatment program and motivational interviewing after climate therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ddg.13840DOI Listing
July 2019

Staging of primary cutaneous follicle centre B-cell lymphoma: bone marrow biopsy, CD10, BCL2 and t(14;18) are not relevant prognostic factors.

Eur J Dermatol 2019 Apr 17. Epub 2019 Apr 17.

Dermatologie, Institut Universitaire du Cancer de Toulouse, Université Paul Sabatier, Hôpital Larrey et Oncopole, Toulouse.

Background: There is a certain degree of controversy as to whether bone marrow biopsy is required during the staging procedures for primary cutaneous follicle centre B-cell lymphoma (PCFCCL).

Objectives: Firstly, to determine extra-cutaneous involvement at initial diagnosis, in particular, based on bone marrow biopsy, and secondly, evaluate the phenotypic features associated with extra-cutaneous involvement during follow-up (in particular, the predictive value of BCL2 and CD10 coexpression and identification of t[14;18] in skin lesions, as well as bone marrow biopsy involvement at initial staging) in a cohort of patients with PCFCCL.

Materials & Methods: A bicentric retrospective study was established to investigate 75 cases of PCFCCL, for which 44 bone marrow biopsies were performed.

Results: Two of 44 (5%) patients had bone marrow involvement. These two patients had no relapse during follow-up, either cutaneous or extra-cutaneous. BCL2 staining in B cells was positive in 39/75 (52%) cases and CD10 was positive in 39/73 (53%). Only 4/26 (15%) cases showed t(14;18) based on fluorescence in situ hybridisation.

Conclusions: Our study combined with data from the literature suggests that systematic bone marrow biopsy at initial staging for putative PCFCCL is not to be recommended. Moreover, BCL2 or CD10 expression does not currently represent a reliable basis to introduce significant changes in initial therapy or the follow-up strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/ejd.2018.3489DOI Listing
April 2019

Efficacy and safety of oral alitretinoin as treatment for chronic hand eczema in France: a real-life open-label study.

Eur J Dermatol 2019 Feb;29(1):59-66

Hôpital Henri Mondor, Dermatologie, Créteil, France.

Background: Chronic hand eczema is an inflammatory dermatosis that results in a significant psychological and socio-economic burden. Alitretinoin (AL) is indicated in adults with severe chronic hand eczema (sCHE) unresponsive to potent topical corticosteroids.

Objectives: To assess AL effectiveness and safety in patients with sCHE under real-life conditions based on a prospective observational study in France (2010-2014).

Materials & Methods: Clinical severity was assessed using Physician Global Assessment (PGA) and Modified Total Lesion Symptom Score (mTLSS) and quality of life by Skindex and visual analogue scales. Patients were treated with AL for 12-24 weeks and followed for 24 months. Responders were patients with clear/almost clear skin based on PGA at the end of treatment and the primary outcome was remission (clear, almost clear, or mild skin) at one and two years after treatment.

Results: A total of 394 patients with severe or moderate PGA were included in the study by 109 dermatologists. AL treatment duration was 5.4 ± 4.1 months (mean ± SD) and 112/274 patients evaluated at the end of treatment were responders. Of the 112 responders, 41/51 evaluable patients were in remission after one year and 36/46 after two years. At the end of treatment, Skindex improved from 48.8 ± 18.1% to 27.1 ± 23.2%. Among the 112 responders, 68/84 did not relapse (mTLSS increased >75% from baseline). The most common adverse events were headache (24%) and dyslipidaemia (4%).

Conclusions: This study supports a positive benefit/risk profile for AL for sCHE patients unresponsive to topical corticosteroids.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/ejd.2018.3484DOI Listing
February 2019

Compounded topical preparations in plaque psoriasis: Still a place for it in 2018?

Dermatol Ther 2019 01 28;32(1):e12780. Epub 2018 Nov 28.

Dermatologie, Université Paul Sabatier, CHU Toulouse, Toulouse, France.

Compounded topical preparations (CTP) were used to treat psoriasis until the last century and have disappeared from guidelines. The present authors report two severe psoriasis patients who were treated with CTP. A man had psoriasis with a PASI of 23 and a body surface area (BSA) of 43%. He had been using daily for several weeks a CTP including minoxidil, clobetasol propionate and hydroxyprogesterone formulated in an alcohol based vehicle. A woman suffered from psoriasis with an annular inflammatory pattern and a central healing. The PASI was 20 and the BSA was 30%. She had been using a CTP daily for 4 months including resorcinol, salicylic acid, 0.05% tretinoin cream, bethamethasone dipropionate cream. Until the 1970s, the dermatological textbooks recommended to treat severe psoriasis with CTP. Nowadays, CTP are considered outdated because of the large therapeutic armamentarium. The stability and benefit risks of the CTP used here were not documented. The use of CTP in psoriasis should be regulated and must be evidence based. Strict protocol and stability evaluation for preparations must be confirmed prior to compounding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dth.12780DOI Listing
January 2019

Large International Validation of ABSIS and PDAI Pemphigus Severity Scores.

J Invest Dermatol 2019 01 6;139(1):31-37. Epub 2018 Oct 6.

Department of Dermatology, Rouen University Hospital, and INSERM U 1234, Centre de référence des maladies bulleuses autoimmunes, Normandie University, Rouen, France.

The Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity-Score (ABSIS) scores have been proposed to provide an objective measure of pemphigus activity. These scores have been evaluated only on already treated patients mainly with mild to moderate activity. The objective was to assess the interrater reliability of ABSIS and PDAI scores and their correlation with other severity markers in a large international study. Consecutive patients with newly diagnosed pemphigus were enrolled in 31 centers. Severity scores were recorded during a 24-month period by the same two blinded investigators. Serum was collected at each visit for ELISA measurement of anti-desmoglein antibodies. The intraclass correlation coefficient (ICC) and Spearman rank correlation coefficient were calculated. A total of 116 patients with pemphigus vulgaris (n = 84) or pemphigus foliaceus (n = 32) were included. At baseline, the ABSIS and PDAI ICCs were 0.90 (95% confidence interval [CI] = 0.85-0.93), and 0.91(95% CI = 0.87-0.94), respectively. The ICCs for PDAI were higher in moderate and extensive pemphigus (ICC = 0.82, 95% CI = 0.63-0.92 and ICC = 0.80, 95% CI = 0.62-0.90, respectively) than in patients with intermediate (significant) extent (ICC = 0.50, 95% CI = 0.27-0.68). Conversely, the ICCs for ABSIS were lower in patients with moderate extent (ICC = 0.44, 95% CI = 0.004-0.74) than in those with intermediate or extensive forms, (ICC = 0.69, 95% CI = 0.51-0.81 and ICC = 0.75, 95% CI = 0.51-0.88, respectively). During patients' follow-up, the ICCs of both ABSIS and PDAI scores remained higher than 0.70. ABSIS and PDAI skin (r = 0.71 and r = 0.75) but not mucosal (r = 0.32 and r = 0.37) subscores were correlated with the evolution of anti-DSG1 and anti-DSG3 ELISA values, respectively. ABSIS and PDAI scores are robust tools to accurately assess pemphigus activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2018.04.042DOI Listing
January 2019

Characterization and Outcomes of Disease Progression in 52 Patients Treated with BRAF-V600 + MEK Inhibitors for Advanced Melanoma.

Dermatology 2018 15;234(3-4):92-98. Epub 2018 Aug 15.

Background: Combined treatment with BRAF-V600 and MEK inhibitors has significantly improved progression-free and overall survival of patients with BRAF-mutated melanoma. Pattern of disease progression and outcomes in patients have not been fully characterized.

Methods: We conducted a single-center, retrospective, descriptive analysis of a cohort of 52 patients treated with BRAF-V600 + MEK inhibitors for advanced melanoma over a 12-month period. The aim of this study was to characterize disease progression, defined as metastatic pattern, disease kinetics, and response to subsequent therapies, in melanoma patients treated with BRAF-V600 + MEK inhibitors.

Results: Disease progression was observed in 31/52 (59.6%) patients treated with BRAF-V600 + MEK inhibitors. Relapse of melanoma involved the CNS for 22/31 (70.9%) patients with disease progression, including 18/31 (58%) patients who had exclusive intracranial metastases. Sixteen patients died from disease progression. Among the 31 patients who had disease progression, the median time until a relapse was 8 months, and the median survival time after disease progression was 2 months.

Conclusion: Our study shows that, for patients treated with BRAF-V600 + MEK inhibitors who lose response, disease progression was aggressive and had poor outcomes. Most patients had CNS metastases and low rates of therapeutic response to any subsequent therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000490891DOI Listing
December 2018

Mast cell activation syndrome: High frequency of skin manifestations and anaphylactic shock.

Allergol Int 2019 Jan 7;68(1):119-121. Epub 2018 Aug 7.

Mastocytosis National Reference Center (CEREMAST), Department of Dermatology, Toulouse University Hospital, Paul Sabatier University, Toulouse, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.alit.2018.07.003DOI Listing
January 2019