Treatment of moderate-to-severe psoriasis in adults: An expert consensus statement using a Delphi method to produce a decision-making algorithm.

BACKGROUND: New highly effective drugs for moderate-to-severe cutaneous psoriasis are regularly marketed, and the hierarchy of treatments thus requires frequent review. OBJECTIVES: A Delphi method was used to enable a structured expert consensus on the use of systemic treatments and phototherapy among adults with moderate-to-severe psoriasis. METHODS: The Delphi method consists in achieving a convergence of opinions among a panel of experts using several rounds of questionnaires with controlled feedback between rounds. A two-part Delphi questionnaire was administered online to French psoriasis experts. In the first part, 180 items related to the prescription of systemic treatments and phototherapy for adult patients with moderate-to-severe psoriasis were grouped into 21 sections covering different lines of treatment and different forms of cutaneous psoriasis. The experts voted on each proposal using an ordinal 7-point Likert scale. The second part comprised 11 open-ended questions about special indications for each therapeutic class. These were converted into 101 questions for subsequent rounds. Consensus was deemed to have been reached if more than 80% of the experts agreed with a given proposal. RESULTS: Three rounds of questionnaires were sequentially sent to 35 participants between November 2021 and March 2022. Thirty-three (94%) completed all three rounds. For plaque psoriasis, only methotrexate was recommended by the experts as first-line systemic treatment (89% of votes). Cyclosporin was advocated in pustular and erythrodermic psoriasis, and acitretin was suggested for hyperkeratotic and palmoplantar psoriasis. In the event of failure of or intolerance to non-biological systemic treatments, guselkumab, risankizumab, ixekizumab or secukinumab were recommended by more than 80% of the experts. Tumor Necrosis Factor (TNF) inhibitors remain useful for patients with cardiovascular risk factors. Special indications were provided for each therapeutic class (methotrexate/narrowband ultraviolet B phototherapy, psoralen/ultraviolet A phototherapy, cyclosporin, acitretin, apremilast, TNF inhibitors, interleukin (IL)-12/23 inhibitors, IL-17(R)A inhibitors, and IL-23 inhibitors). CONCLUSIONS: This expert consensus statement indicate that newly available IL-17 and IL-23 inhibitors may be favored over TNF and IL-12/23 inhibitors as first-line biologics. The Centre of Evidence of the French Society of Dermatology has drawn up a decision-making algorithm to guide clinicians in the therapeutic management of moderate-to-severe psoriasis.

Effectiveness of mogamulizumab in patients with Mycosis Fungoides or Sézary syndrome: A multicentre, retrospective, real-world French study.

BACKGROUND: Efficacy and safety of mogamulizumab, a monoclonal antibody directed against C-C chemokine receptor 4, were demonstrated in a previous multinational clinical trial conducted in patients with previously treated cutaneous T-cell lymphoma (CTCL): Sézary syndrome (SS) or Mycosis Fungoides (MF). OBJECTIVES: The real-world French OMEGA study aimed to describe effectiveness and tolerability of mogamulizumab in adult patients with CTCL, overall and according to the disease (SS or MF). METHODS: In this retrospective study, patients treated with mogamulizumab for SS or MF were included from 14 French expert centres. The overall response rate (ORR) under treatment was described (primary criterion), as well as treatment use and safety data. RESULTS: The 122 analysed patients (69 SS, 53 MF) were aged 66.6 ± 12.1 years at mogamulizumab initiation, and their median disease duration was 2.5 years (IQR: 1.3-5.6). Prior to treatment start, they received a median of three systemic CTCL therapies (2-5). Overall, 77.8% of patients suffered from advanced disease (Stage IIB-IVB), with frequent blood (B1/B2) involvement (67.5%). Over the treatment period (median: 4.6 months, 2.1-7.2), 96.7% of patients received all the planned mogamulizumab infusions. Among the 109 patients evaluable for effectiveness, ORR was 58.7% (95% CI [48.9-68.1]) overall, 69.5% [56.1-80.8] in SS and 46.0% [31.8-60.7] in MF. Compartmental response in the blood was observed in 81.8% [69.1-90.9] of SS patients. Skin responses were observed in 57.0% [47.0-66.5] of patients overall, 66.7% [52.9-78.6] in SS and 46.0% [31.8-60.7] in MF. The most common serious adverse drug reactions were rash (8.1% of patients) and infusion-related reactions (2.4%) which led to treatment discontinuation in 7.3% and 0.8% of patients, respectively. One patient with SS died from mogamulizumab-related tumour lysis syndrome. CONCLUSIONS: This large French study confirmed the effectiveness and tolerability of mogamulizumab in SS and MF patients in routine medical practice.

Safety and efficacy of the anti-PD1 immunotherapy with nivolumab in trichoblastic carcinomas.

Trichoblastic carcinoma is a rare malignant cutaneous adnexal tumor with a risk of local invasion and distant metastasis. As of today, there is no consensus for the treatment of locally advanced or metastatic trichoblastic carcinoma. "AcSé Nivolumab" is a multi-center Phase II basket clinical trial (NCT03012581) evaluating the safety and efficacy of nivolumab in several cohorts of rare, advanced cancers. Here we report the results of nivolumab in patients with trichoblastic carcinoma. Of the eleven patients enrolled in the study, five patients had been previously treated by sonic hedgehog inhibitors. The primary endpoint 12-week objective response rate was 9.1% (N = 1/11) with 1 partial response. Six patients who progressed under previous lines of treatment showed stable disease at 12 weeks, reflecting a good control of the disease with nivolumab. Furthermore, 54.5% of the patients (N = 6/11) had their disease under control at 6 months. The 1-year overall survival was 80%, and the median progression-free survival was 8.4 months (95%CI, 5.7 to NA). With 2 responders (2 complete responses), the best response rate to nivolumab at any time was 18.2% (95%CI, 2.3-51.8%). No new safety signals were identified, and adverse events observed herein were previously described and well known with nivolumab monotherapy. These results are promising, suggesting that nivolumab might be an option for patients with advanced trichoblastic carcinomas. Further studies on larger cohorts are necessary to confirm these results and define the role of nivolumab in the treatment of trichoblastic carcinomas.

Switches between biologics in patients with moderate-to-severe psoriasis: results from the French cohort PSOBIOTEQ.

BACKGROUND: Biologics are the cornerstone of treatment of patients with moderate-to-severe plaque psoriasis and switches between biologics are frequently needed to maintain clinical improvement over time. OBJECTIVES: The main purpose of this study was to describe precisely switches between biologics and how their pattern changed over time with the recent availability of new biologic agents. METHODS: We included patients receiving a first biologic agent in the Psobioteq multicenter cohort of adults with moderate-to-severe psoriasis receiving systemic treatment. We described switches between biologics with chronograms, Sankey and Sunburst diagrams, assessed cumulative incidence of first switch by competing risks survival analysis and reasons for switching. We assessed the factors associated with the type of switch (intra-class - i.e. within the same therapeutic class - vs. inter-class) in patients switching from a TNF-alpha inhibitor using multivariate logistic regression. RESULTS: A total of 2153 patients was included. The cumulative incidence of switches from first biologic was 34% at 3 years. Adalimumab and ustekinumab were the most prescribed biologic agents as first and second lines of treatment. The main reason for switching was loss of efficacy (72%), followed by adverse events (11%). Patients receiving a TNF-alpha inhibitor before 2016 mostly switched to ustekinumab, whereas those switching in 2016 or after mostly switched to an IL-17 inhibitor. Patients switching from a first-line TNF-alpha inhibitor before 2016 were more likely to switch to another TNF-alpha inhibitor compared with patients switching since 2018. Patients switching from etanercept were more likely to receive another TNF-alpha inhibitor rather than another therapeutic class of bDMARD compared with patients switching from adalimumab. CONCLUSION: This study described the switching patterns of biologic treatments and showed how they changed over time, due to the availability of the new biologic agents primarily IL-17 inhibitors.

Clinical features associated with the invasive component in lentigo maligna of the head and neck: A retrospective study of 175 cases.

BACKGROUND: Lentigo maligna (LM) can develop into lentigo maligna melanoma (LMM) with risk of metastatic dissemination. LMM may be underestimated on the basis of the initial biopsy. The invasion may affect both the therapeutic options and the prognosis. OBJECTIVES: To identify the clinical features associated with invasive forms of LM and factors associated with its recurrence. METHODS: A retrospective, single-centre study of consecutive LM and LMM histologically confirmed and treated by surgery between 2009 and 2014. RESULTS: In total, 175 patients with LM/LMM were surgically treated in our establishment. In men, lesions were more likely to be in the "peripheral zone" (41.8%), while in women they were seen more often in the "central zone" (P=0.001). In multivariate analysis, only the peripheral zone was found to be associated with a risk of invasion (P=0.008). The rate of recurrence was 9% and lesions were more likely to be primary LMM (P=0.0006) excised with clear margins. CONCLUSION: The treatment of choice in LM with non-clear margins must be re-excision, especially for lesions situated in the peripheral zone. Close follow-up is recommended due to risk of recurrence, even in the case of clear margins.

Changes in total skin electron beam therapy modalities for mycosis fungoides: A single-centre study.

BACKGROUND: Mycosis fungoides (MF) is a highly radiosensitive disease. Total skin electron beam therapy (TSEBT) is an effective option that may allow prolonged response for several months. Recently, a low-dose regimen (12 Gy) has been reported more frequently, with less complete response than for standard doses (36 Gy) but better safety. Our aim was to compare patients treated with 12-Gy and 36-40-Gy TSEBT regimens at our centre for efficacy and safety. METHODS: This retrospective, monocentric study in Bordeaux University Hospital included all MF patients treated with 12-Gy or 36-40-Gy TSEBT between 2011 and 2020. RESULTS: Patients presented with MF at the following stages: 15 T2, including 9 folliculotropic MF; 2 T3, including 1 folliculotropic; 8 T4, including 2 Sézary syndromes. The mean follow-up time after TSEBT was 43.5 months [range: 2-128] for the 36-40-Gy group and 25.2 months [range: 4-45] for the 12-Gy group. The 3-month overall response rate (ORR) was similar for both groups (84.6% for 36-40 Gy and 91.7% for 12 Gy), but there was a tendency to more complete response in the 36-40-Gy group (30.8% vs 8.3%, P=0.35). Progression-free survival (PFS) tended to be better in the 36-40-Gy group than in the low-dose group (15.7 months vs 5.3 months; P=0.28). Patients treated with low-dose TSEBT had a lower incidence of radiation dermatitis (16.7% vs 38.4%, P=0.42). CONCLUSION: We confirm that TSEBT is an effective option, including at lower doses. Differences between low- and standard-dose regimens were not significant in our series. Although a low-dose regimen seemed to result in lower complete response and long-term efficacy rates in comparison with a standard dose, treatment at lower doses presents the advantage of repeatability, with fewer and weaker side effects, in the event of disease recurrence. Second-line treatments were mostly skin-directed in this group.

Evolution of bone metastases in patients receiving at least three months of checkpoint inhibitors.

BACKGROUND: To investigate the evolution of bone metastases in patients receiving immune checkpoint inhibitors (ICI). METHODS: A single-center retrospective study included cancer patients with bone metastases treated with ICI at our institution between January 2014 and September 2019. Clinical and biological data were collected from medical records and independent expert review of imaging was performed. Target and non-target lesions were identified and followed up to 1 year. Patients were then classified as bone responder or non-responder. Comparisons between groups were performed with Student's t test or Mann-Whitney test. RESULTS: Among 1108 patients screened, 192 patients had bone metastases and 48 patients were included in the final analysis, with lung cancer, renal carcinoma and melanoma as most represented cancer type. Half of the patients experienced stability, condensation or peripheral sclerosis of bone lesions. Initial progression before stabilization with or without sclerosis of bone lesion occurred for 19% of patients (pseudoprogression). There was an association between bone response and global oncological outcomes. Bone responder patients had a significant decrease in morphine and co-analgesic prescription as well as a significant decrease in alkaline phosphatases compared to non-responder patients. CONCLUSION: Bone response was observed in half of patients with available imaging and follow-up after 3 months of ICI treatment, with sclerosis observed in one-third of bone lesions at month 3, in all tumor types. Up to 20% of patients experienced a pseudoprogression of bone lesions such as previously described in primary tumor and other metastatic sites. Bone response was associated with improvement of pain and survival.

How to Manage Inflammatory Bowel Disease Patients When They Withdraw Anti-Tumour Necrosis Factor [Anti-TNF] Due to Severe Anti-TNF-Induced Skin Lesions? A Multicentre Cohort Study.

BACKGROUND AND AIMS: Optimal management of patients with inflammatory bowel disease [IBD] after anti-tumour necrosis factor [TNF] discontinuation due to severe induced skin lesions is unclear. Our study aimed to describe dermatological and IBD evolution after anti-TNF discontinuation for this side effect. METHODS: We conducted a multicentre retrospective study including consecutive IBD patients who discontinued anti-TNF due to severe induced skin lesions. Our objectives were to determine factors associated with dermatological remission [complete disappearance of skin lesions] and with IBD relapse in patients with inactive disease at inclusion, notably the impact of an early switch to another biological agent within 3 months of anti-TNF discontinuation. RESULTS: Among the 181 patients [134 women, 160 Crohn's disease] included in the 13 participating centres, dermatological remission occurred in 110 [62%] patients with a median [interquartile range, IQR] interval of 8.0 [6.8-11.0] months. Scalp location was independently associated with less remission of skin lesions (hazard ratio [HR] = 0.64 [95% CI 0.43-0.94], p = 0.02) while early switch was independently associated with a higher probability of remission of skin lesions (HR = 1.64 [95% CI 1.1-2.5], p = 0.02). Among the 148 patients with inactive IBD at inclusion, disease relapse occurred in 75 [51%] patients with a median [IQR] interval of 26.0 [23.0-39.1] months. Survival rates without IBD relapse at 1 year were 85.8% [95% CI 77.5-94.9] in the early switch group and 59.3% [95% CI 48.9-71.9] in the other group [p < 0.01]. CONCLUSIONS: Early switch to a new biological is associated with a higher probability of healing of anti-TNF-induced skin lesions and significantly reduces the risk of IBD relapse.

Epidemiology of cutaneous malignant melanoma in Reunion Island.

INTRODUCTION: The incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. The aim of this study was to evaluate the epidemiology of CMM in Reunion Island, a French overseas department whose population is characterized by high ethnic diversity and high exposure to ultraviolet radiation. METHODS: This cross-sectional study examined all cases of in situ CMM and invasive CMM diagnosed between 1 January and 31 December 2015 in the Reunionese population. RESULTS: One hundred and three new cases of CMM were recorded in Reunion Island in 2015: 33 cases of in situ CMM and 70 cases of invasive CMM. The sex ratio of men to women was 1.3 and 80% of patients had a fair skin phototype (Fitzpatrick skin phototype≤III). Age-standardized incidence rates of invasive CMM for all skin phototypes combined were 6.7/100,000 person-years (PY) in women and 5.3/100,000 PY in men. Crude incidence rates of invasive CMM for fair skin phototypes were estimated to be over 21/100,000 PY in women and over 25/100,000 PY in men. CONCLUSIONS: In Reunion Island, the incidence of CMM in the population with fair skin phototype is very high. Primary and secondary prevention measures should be reinforced and tailored to the local context.

From neglect to earlier diagnosis: a qualitative meta-synthesis of psycho-social factors associated with consultation delay in advanced basal cell carcinoma.

Local malignant potential of basal cell carcinoma (BCC) can lead at advanced stages to the destruction of underlying tissues and significant morbidity. The primary risk factor for progression of advanced basal cell carcinoma (aBCC) is the long duration of the tumour, which results from delay in seeking medical care. To assess the implication of psycho-social factors in the delay before the first medical consultation among patients with aBCC, in order to identify potentially targetable factors enabling earlier diagnosis. Three-step qualitative meta-synthesis: (1) systematic review of the literature; (2) structured qualitative analysis of these documents; (3) construction of a logical model. After screening, 81 articles were included. Self-neglect and denial in patients are roundly put forward as the main obstacles to consultation. We found that avoidance behaviour, mistaken interpretation and banalisation of symptoms, and fear of treatment all played a role. The strongest motivation to seek help comes from the realisation that new symptoms may be dangerous; the role of interpersonal surroundings is highlighted as helpful. Patient delay has multifactorial origins in aBCC, especially self-neglect ranging from denial of tumours to conscious refusal of treatment.

Efficacy of sonic hedgehog inhibitors rechallenge, after initial complete response in recurrent advanced basal cell carcinoma: a retrospective study from the CARADERM database.

BACKGROUND: Smoothened (SMO) inhibitors, blocking the sonic hedgehog pathway, have been approved for advanced basal cell carcinoma (aBCC). Safety analyses reveal a high rate of adverse events (AEs) and, most of the time, vismodegib is most commonly stopped when the best overall response is reached. The long-term evolution of aBCC after vismodegib discontinuation is poorly described. The aim of this study is to evaluate the efficacy and safety of the SMO inhibitors (SMOis) available (vismodegib and sonidegib) following rechallenge after complete response (CR) following an initial treatment by vismodegib. MATERIALS AND METHODS: This real-life, retrospective, multicenter and descriptive study is based on an extraction from the CARADERM accredited database, including 40 French regional hospitals, of patients requiring BCC systemic treatment. RESULTS: Of 303 patients treated with vismodegib, 110 achieved an initial CR. The vast majority of these patients (98.2%) stopped vismodegib, notably due to poorly tolerated AEs. The CARADERM database provided a median follow-up of 21 months (13.5-36.0 months) after CR. Of the 110 patients, 48.1% relapsed after a median relapse-free survival of 24 months (13.0-38.0 months). Among them, 35 patients were retreated by an SMOi and the overall response rate was 65.7% (34.3% of CR and 31.4% of partial response). The median duration of retreatment was 6.0 months (4.0-9.5 months). CONCLUSION: Our real-life study, carried out on patients with complex clinical pictures, shows that after treatment discontinuation, 48.1% of patients achieved CR relapse within an average of 24 months (13.0-38.0 months). It emphasized that even though rechallenge can be considered as a therapeutic option, efficacy seems to decrease, suggesting the development of resistance mechanisms.

Surgical treatment of rhinophyma: Retrospective monocentric study and literature review.

BACKGROUND: Treatment of rhinophyma consists primarily of destructive procedures. There is currently no consensus regarding treatment. In this study, we propose an algorithm based on a cohort of 25 patients and a literature review. PATIENTS AND METHODS: This was a retrospective study conducted between January 2016 and December 2018. The cosmetic outcome was evaluated by 2 independent assessors based on pre- and postoperative photographs. Patients were ranked according to the severity (mild, moderate, severe) of their rhinophyma. The different surgical methods used were cold blade excision or rhinoshave, electrosurgery or monopolar diathermy knife (MDK), and carbon dioxide laser (CO2 laser), either alone or in combination with another technique. All patients were contacted after the procedure to evaluate their satisfaction and to investigate for adverse effects. RESULTS: Twenty-five patients were included retrospectively: 7 with mild rhinophyma (5 were treated by MDK, 1 by fractional CO2 laser, and 1 by cold-blade excision and TCA solution), 11 with moderate rhinophyma (2 were treated by MDK, 9 by continuous CO2 laser), and 7 with severe rhinophyma (2 were treated by MDK, 5 by MDK plus CO2 laser). Cosmetic outcomes were deemed good or excellent in 80% of cases, and 84% of patients were fully satisfied with the result. We observed 5 cases of hypertrophic scarring, 2 cases of hypopigmentation, 3 cases of notching of the nasal ala, and 7 cases of prolonged erythema, most of which were caused by the MDK technique. CONCLUSION: A wide range of treatment options are available for rhinophyma. We suggest the use of cold-blade excision and trichloroacetic acid or fractional carbon dioxide laser for mild rhinophyma, continuous and pulsed CO2 laser for moderate rhinophyma, and MDK for severe rhinophyma.

Clinicopathologic analysis of trichoblastoma and comparison with nodular basal cell carcinoma.

BACKGROUND: Trichoblastoma (TB) is an uncommon benign follicular tumour for which clinical data is limited since most reports originate from pathology studies. OBJECTIVE: To describe the clinical aspects of TB. METHODS: This is an ancillary study of a prospective multicentre cohort of 2710 clinically suspected basal cell carcinoma (BCC), including 935 nodular BCCs. Sixty-two cases were TB: they were analysed and compared to 935 nodular BCCs. RESULTS: TB mostly occurred in females (61% vs. 43% for BCC, P<0.01) of mean age 63 years. They were located on the head and neck, mainly on the nose and forehead, in 87% of cases. The mean size was 8.1mm, 77% were<10mm (55% of BCCs, P<0.001), 8% were ulcerated (vs. 21% of BCCs, P<0.02), and 47% persisted for more than 1 year (34% of BCCs, P<0.05). Most cases had a clinical presentation similar to nodular BCC, except for 5 small, flat, white papules and 1 anfractuous plaque. LIMITATIONS: Cases originated from a series of tumours clinically suspected as BCCs. DISCUSSION: Some 2.6% of tumours clinically diagnosed as BCC are in fact TB. TB occurs on the head, are more frequent in women, and are smaller and of longer duration than BCC. In most cases, clinical diagnosis on clinical grounds is difficult.

Lymphomatoid papulosis types D and E: a multicentre series of the French Cutaneous Lymphomas Study Group.

BACKGROUND: Lymphomatoid papulosis (LyP) type D (LyP D) and type E (LyP E) have recently been described in small series of cases or isolated case reports. AIM: To further describe the clinical and histological features of LyP D and E based on a retrospective multicentre study. METHODS: The clinical and histopathological features of 29 patients with an initial diagnosis of LyP D or LyP E were retrospectively assessed using standardized forms. RESULTS: After exclusion of 5 cases, 24 patients (14 LyP D, 10 LyP E) were enrolled in the study. The median follow-up was 2.5 years (range 1 month to 13 years). LyP D was characterized by multiple recurrent self-regressing small papules that developed central erosion or necrosis, whereas LyP E presented as papulonodular lesions that rapidly evolved into necrotic eschar-like lesions > 10 mm in size. Epidermal changes were more frequent in LyP D, whereas dermal infiltrates were deeper in LyP E. Anaplastic cytology was rare and the DUSP22 rearrangement was never observed. Two patients (8%) had an associated cutaneous lymphoma. CONCLUSION: LyP D and E have distinct clinical findings and may be associated with other cutaneous lymphomas.

Relevance of body mass index as a predictor of systemic therapy outcomes in metastatic melanoma: analysis of the MelBase French cohort data☆.

BACKGROUND: The 'obesity paradox' suggests that higher body mass index (BMI) is associated with better survival values in metastatic melanoma patients, especially those receiving targeted and immune checkpoint inhibitor therapy. Higher BMI is also associated with higher incidences of treatment-related adverse events (TRAEs). This study assesses whether BMI is associated with survival outcomes and adverse events in metastatic melanoma patients with systemic therapy. PATIENTS AND METHODS: This multicentric retrospective study, conducted from 1 March 2013 to 29 April 2019, enrolled adults with unresectable stage III or IV melanoma from the French multicentric prospective cohort-MelBase (NCT02828202). Patients with first-line chemotherapy and targeted and immune therapy were included. Underweight people and those with metastatic mucosal or ocular melanoma were excluded. BMI was categorized using the World Health Organization criteria. Co-primary outcomes included the association between BMI and progression-free survival and overall survival, stratified by treatment type, sex, and age. Secondary endpoints were the association of BMI with overall response and TRAEs. Multivariate analyses were carried out. RESULTS: A total of 1214 patients were analyzed. Their median age was 66.0 years (range, 53-75). Male predominance was observed [n = 738 (61%)]. Most patients received immune checkpoint inhibitor therapy (63%), followed by targeted therapy (32%), and had stage M1c disease (60.5%). Obese patients represented 22% of the cohort. The median follow-up duration was 13.5 months (range, 6.0-27.5). In the pooled analysis, no positive or negative association between BMI and progression-free survival (P = 0.88)/overall survival (P = 0.25) was observed, regardless of treatment type, sex, and age. These results were nonsignificant in the univariate and multivariate analyses. The objective response rate, according to BMI category, did not differ significantly regardless of age. TRAEs were not associated with BMI. CONCLUSION: The observed lack of an association between BMI and survival demonstrates that BMI is not a valuable marker of systemic treatment-related outcomes in metastatic melanoma. Future approaches might focus on the whole-body distribution.