Lower-limb ulcers in systemic sclerosis patients are rarely reported. The aim of this study was to describe the main causes and outcomes of lower-limb ulcers in systemic sclerosis patients and to ...assess factors associated with ischemic causes (arterial disease and/or microvascular impairment). A retrospective, multicentre, case-control study was conducted in 2013 and 2014, including 45 systemic sclerosis patients presenting lower-limb ulcers between 2008 and 2013. The estimated prevalence of lower-limb ulcers among systemic sclerosis patients was 12.8%. Ulcers were related to venous insufficiency in 22 cases (49%), ischemic causes in 21 (47%) and other causes in 2 (4%). Complete healing was observed in 60% of cases in a mean time of 10.3 months; 59% relapsed during a mean follow-up of 22 months. Ischemic lower-limb ulcers outcomes were poor, with a 28.6% amputation rate. Logistic-regression multivariate analyses between ischemic lower-limb ulcers cases and matched systemic sclerosis-controls identified past or concomitant digital ulcer and cutaneous sclerosis of the feet as independent risk factors associated with ischemic lower-limb ulcers.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Dose tapering strategies with biologics in psoriasis may lower the treatment burden over time, while enabling high therapeutic response maintenance in patients benefiting from them. Our results ...should contribute to developing clinical guidelines to fill the current gap in knowledge on this promising therapeutic approach
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BFBNIB, FZAB, GIS, IJS, KILJ, OILJ, SBCE, SBMB, UPUK
Cutaneous microcystic lymphatic malformations (CMLMs) are rare conditions in children and adults. They present as clusters of vesicles full of lymph and blood to various extents, inducing maceration, ...esthetic impairment, pain, and impaired quality of life. The treatment is challenging. Sirolimus is an inhibitor of mammalian target of rapamycin (mTOR) involved in angio-lymphangiogenesis. Topical sirolimus has recently been reported as effective in a few reports of patients with CMLMs. The objective is to compare the efficacy and safety of a 12-week application of 0.1% topical sirolimus versus topical vehicle in CMLMs in children and adults.
This French blinded multicenter within-person randomized controlled phase 2 trial aims to include 55 patients aged ≥ 6 years who have a primary CMLM. The CMLM will be divided into two equal areas that will be randomly allocated to 0.1% topical sirolimus or topical vehicle applied for 12 weeks. At the end of the 12-week period, the patient/parent will treat the whole area of CMLM with 0.1% topical sirolimus on remaining lesions, for eight more weeks. Patients will be seen at week 20 (treatment will be stopped) and at month 12 to evaluate long-term efficacy. The primary outcome will be improvement of the CMLM in the area treated with topical sirolimus compared to the area treated with topical vehicle by the investigator physician (blinded to the treatment) with the Physician Global Assessment score at week 12. Secondary outcomes will include: assessment of efficacy by independent experts on the basis of standardized photographs; impact on quality of life; efficacy for oozing, bleeding, erythema, and thickness evaluated by the investigators; and global efficacy as well as efficacy for functional and aesthetic impairment evaluated by the patient. Systemic passage of sirolimus will be measured at weeks 6, 12, and 20, and at week 16 for CMLMs ≥ 900 cm
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For patients with CMLMs, topical sirolimus could be a non-invasive and well-tolerated therapeutic option. If the trial demonstrates efficacy and safety of this treatment, this result will lead to a real change in the management of this condition, and 0.1% sirolimus cream would become the first-line treatment.
ClinicalTrials.gov, NCT03972592. Registered on 3 June 2019. EU Clinical Trials Register EudraCT, 2018-001359-11.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
IMPORTANCE: Rituximab and short-term corticosteroid therapy are the criterion standard treatments for patients with newly diagnosed moderate to severe pemphigus. OBJECTIVE: To examine factors ...associated with short-term relapse in patients with pemphigus treated with rituximab. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of a randomized clinical trial (Comparison Between Rituximab Treatment and Oral Corticosteroid Treatment in Patients With Pemphigus RITUX 3) conducted from January 1, 2010, to December 31, 2015, included patients from 20 dermatology departments of tertiary care centers in France from the RITUX 3 trial and 3 newly diagnosed patients treated according to the trial protocol. Data analysis was performed from February 1 to June 30, 2019. EXPOSURE: Patients randomly assigned to the rituximab group in the RITUX 3 trial and the 3 additional patients were treated with 1000 mg of intravenous rituximab on days 0 and 14 and 500 mg at months 12 and 18 combined with a short-term prednisone regimen. MAIN OUTCOMES AND MEASURES: Baseline (pretreatment) clinical and biological characteristics (Pemphigus Disease Area Index PDAI score, ranging from 0-250 points, with higher values indicating more severe disease) and changes in anti–desmoglein (DSG) 1 and anti-DSG3 values as measured by enzyme-linked immunosorbent assay during the 3 months after rituximab treatment were compared between patients with disease relapse and those who maintained clinical remission during the first 12 months after treatment. The positive and negative predictive values of these factors were calculated. RESULTS: Among 47 patients (mean SD age, 54.3 17.0 years; 17 36% male and 30 64% female) included in the study, the mean (SD) baseline PDAI score for patients with relapsing disease was higher than that of the patients with nonrelapsing disease (54 33 vs 28 24; P = .03). At month 3, 7 of 11 patients with relapsing disease (64%) vs 7 of 36 patients with nonrelapsing disease (19%) had persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher (P = .01). A PDAI score of 45 or higher defining severe pemphigus and/or persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher at month 3 provided a positive predictive value of 50% (95% CI, 27%-73%) and a negative predictive value of 94% (95% CI, 73%-100%) for the occurrence of relapse after rituximab. CONCLUSIONS AND RELEVANCE: The findings suggest that initial PDAI score and changes in anti-DSG antibody values after the initial cycle of rituximab might help differentiate a subgroup of patients with high risk of relapse who might benefit from maintenance rituximab infusion at month 6 from a subgroup of patients with low risk of relapse who do not need early maintenance therapy. TRIAL REGISTRATION: NCT00784589
IMPORTANCE: The Ritux 3 trial demonstrated the short-term efficacy and safety of first-line treatment with rituximab compared with a standard corticosteroid regimen in pemphigus. No data on the ...long-term follow-up of patients who received rituximab as first line are available. OBJECTIVE: To assess the long-term efficacy and safety of the Ritux 3 treatment regimen. DESIGN, SETTING, AND PARTICIPANTS: This 7-year follow-up study of the Ritux 3 trial included patients with pemphigus from 25 dermatology departments in France from January 1, 2010, to December 31, 2015. EXPOSURE: Patients were initially randomized in the rituximab plus prednisone group or prednisone-alone group. MAIN OUTCOMES AND MEASURES: The primary outcome was the 5- and 7-year disease-free survival (DFS) without corticosteroids, assessed by Kaplan-Meier curves. Secondary outcomes were occurrence of relapse, occurrence of severe adverse events (SAEs), and evolution of antidesmoglein (Dsg) antibody enzyme-linked immunosorbent assay values to predict long-term relapse. RESULTS: Of the 90 patients in the Ritux 3 trial, 83 were evaluated at the end of follow-up study visit (44 in the rituximab plus prednisone group; 39 in the prednisone-alone group) with a median (IQR) follow-up of 87.3 (79.1-97.5) months. Forty-three patients (93%) from the rituximab plus prednisone and 17 patients (39%) from the prednisone-alone group had achieved complete remission without corticosteroids at any time during the follow-up. Patients from the rituximab group had much longer 5- and 7-year DFS without corticosteroids than patients from the prednisone-alone group (76.7% and 72.1% vs 35.3% and 35.3%, respectively; P < .001), and had about half the relapses (42.2% vs 83.7%; P < .001). Patients who received rituximab as second-line treatment had shorter DFS than patients treated as first line (P = .007). Fewer SAEs were reported in the rituximab plus prednisone group compared with the prednisone-alone group, 31 vs 58 respectively, corresponding to 0.67 and 1.32 SAEs per patient, respectively (P = .003). The combination of anti-Dsg1 values of 20 or more IU/mL and/or anti-Dsg3 values of 48 or more IU/mL yielded 0.83 positive predictive value and 0.94 negative predictive value to predict long-term relapse. CONCLUSIONS AND RELEVANCE: In this secondary analysis of the Ritux 3 trail, first-line treatment of patients with pemphigus with the Ritux 3 regimen was associated with long-term sustained complete remission without corticosteroid therapy without any additional maintenance infusion of rituximab.
Little is known about phototype and the response to systemic treatment in psoriasis.
To assess the characteristics of psoriasis, the therapeutic choice and its efficacy according to phototype.
We ...included patients from the PsoBioTeq cohort initiating a first biologic. Patients were classified according to their phototype. The evaluation included disease characteristics, choice of the initial biologic and therapeutic response at 12 months based on PASI 90 and DLQI 0/1.
Of the 1400 patients included, 423 (30.2%), 904 (64.6%) and 73 (5.2%) were in the phototype I-II, III-IV and V-VI groups, respectively. The V-VI group had a higher initial DLQI, more frequently initiated ustekinumab. Patients in the phototype V-VI group maintained the first sequence of biologic as the other phototype groups, even though the proportion of patients reaching the PASI 90 and DLQI 0/1 at 12 months was lower in this group than other groups.
Patient phototype seems associated with quality of life and choice of the initial biologic in psoriasis. Phototype V-VI group less frequently switched treatments than did the other groups when the response was not efficient.
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BFBNIB, FZAB, GIS, IJS, KILJ, OILJ, SBCE, SBMB, UPUK
This retrospective observational study aimed to determine the effectiveness, safety and patterns of the use of nivolumab in patients with advanced melanoma in real‐world clinical practice in France ...using data from a Temporary Authorization for Use Program (ATU). Data were collected from patients with unresectable or metastatic melanoma enrolled in a French national database (Réseau pour la Recherche et l'Investigation Clinique sur le Mélanome: Ric‐Mel) and treated with nivolumab during the ATU program (12 September 2014 to 31 August 2015). The primary objectives of the study were to evaluate the effect of patient characteristics on clinical response and overall survival (OS). Among 400 included patients (median age 66 years), the majority (83%) received nivolumab as second‐ or subsequent‐line therapy. The median durations of progression‐free survival and OS were 3.3 and 14.1 months, respectively, and 31.6% of patients achieved an objective response with a median duration of 20.1 months (range: 0‐34.7). The safety profile of nivolumab was manageable and consistent with those of previous clinical trials, with an incidence of grade 3‐5 adverse events of 13.8%. The safety and effectiveness of nivolumab in patients with advanced melanoma in real‐world clinical practice in France were in line with the data reported in the Phase 3 trials CheckMate 066 and 037 of nivolumab in this patient population.
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Clinical trial data support the use of nivolumab in melanoma patients, and the drug received a Temporary Authorization for Use in France. Here, the authors present real‐world clinical data on the safety and efficacy of nivolumab collected from 400 patients with unresectable or metastatic melanoma. They found that the safety and efficacy in the real world context was consistent with the profile reported in phase 3 trials. The study also includes data from some sub‐populations that may have been underrepresented in the clinical trials.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Patients with an inherited autosomal-dominant disorder, capillary malformation-arteriovenous malformation (CM-AVM), frequently have mutations in Ras P21 protein activator 1 (RASA1). The aims of this ...study were to determine the prevalence of germline RASA1 variants in a French multicentre national cohort of children, age range 2-12 years, with sporadic occurrence of capillary malformation (CM) of the legs, whatever the associated abnormalities, and to identify genotype-phenotype correlates. DNA was extracted from leukocytes in blood samples, purified and amplified, and all exons of the RASA1 gene were analysed. Among 113 children analysed, 7 had heterozygous variants (6.1%). Four different variants were identified; 2 were new. In children with RASA1 variants, CMs were more frequently bilateral and multifocal. In conclusion, RASA1 variants are rarely found in children with sporadic CM of lower limbs without CM-AVM syndrome. CMs in this study were heterogeneous, and no disease-causing relationship could be proven.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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