Identification of clinical predictors for dupilumab dose spacing in adults with atopic dermatitis: a real-world study.

BACKGROUND: Dupilumab is a monoclonal antibody against the IL-4/IL-13 receptor-subunit approved for the treatment of moderate-severe atopic dermatitis (AD). Some attempts to increase dose interval have been described in both trial and real-world settings. OBJECTIVE: This study aimed to identify predictive clinical and demographic factors affecting patient selection for dose spacing or treatment withdrawal due to satisfactory response. MATERIALS AND METHODS: This retrospective study included adult patients with moderate-to-severe AD treated with dupilumab for at least 16 weeks. Descriptive statistics were performed to analyze demographic and clinical variables. Logistic regression models were used to identify predictor variables. RESULTS: A total of 818 adult patients with moderate-to-severe AD was included in the study and 12% (97/818) of them performed dose spacing to 3-4 weeks or treatment withdrawal (8%, 67/818). The presence of non-cutaneous atopic manifestations (OR = 1.59, 95%CI = 1.06-2.38, p = 0.024), prurigo nodularis phenotype (OR = 4.5, 95%CI = 1.87-10.9, p = 0.001) and the age at treatment initiation (OR = 1.82, 95%CI = 1.12-2.94, p = 0.015) were confirmed as the strongest predictors of dose spacing or treatment withdrawal while maintaining dupilumab effectiveness. CONCLUSION: Our findings contribute to define the patient profile that could maintain the therapeutic response after dose spacing or treatment withdrawal.

Predicting factors identified patients with dupilumab who could benefit of dose spacing or treatment withdrawal.

Drug survival of dupilumab compared to cyclosporin in moderate-to-severe atopic dermatitis patients.

Dupilumab and cyclosporin are recommended treatments for moderate-to-severe atopic dermatitis (AD). The objective of this study was to investigate drug survival of dupilumab in comparison with CsA, reasons of drug discontinuation, and predictive parameters of drug survival in daily practice. Retrospective study including patients with moderate-to-severe AD treated with dupilumab or cyclosporin (CsA) from January 1, 2019 to April 30, 2020. Drug survival analysis was performed using the Kaplan-Meier method and predictive factors were analyzed using multivariate Cox regression analyses. Adult patients with AD (n = 251) treated with dupilumab (n = 149) or CsA (n = 102) were included. Sixteen months from baseline, 82% of patients receiving dupilumab were still on treatment vs 11% of those treated with CsA. Reason for withdrawing dupilumab were primary inefficacy in 4.7% of patients, persistent clinical remission in 7.4%, and cutaneous adverse effects in 2.0%. Older age at diagnosis and shorter AD duration predicted shorter dupilumab survival. Reasons for CsA withdrawal included adverse effects in 23.5% of patients, persistent clinical remission in 15.6%, and a minimal or absent improvement in 11.7%. Dupilumab has a longer drug survival compared to CsA. Only a limited number of dupilumab patients discontinued treatment due to adverse effects and/or ineffectiveness.

Psoriatic Arthritis and Diabetes Mellitus: A Narrative Review.

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory spondyloarthropathy associated with psoriasis. PsA is frequently associated with metabolic disorders including, obesity, metabolic syndrome, and diabetes mellitus (DM). Type 2 DM is among the most common metabolic disorders, with a prevalence ranging from 2.4 to 14.8% in the general population. METHODS: We conducted a narrative review of the English-language studies from January 1989 to September 2019 investigating the risk of type 2 DM in patients with PsA, the pathogenic mechanism linking DM to PsA, and the effects on insulin sensitivity exerted by systemic therapies for PsA. RESULTS: The prevalence of type 2 DM in patients with PsA ranges from 6.1 to 20.2%, generally higher when compared to the general population. The higher risk of DM is reported in women with more severe forms of PsA. Elevated serum levels of adipokines, including TNF-α, which inhibits the autophosphorylation of the insulin receptor and suppresses the expression of glucose transporter 4, favor insulin resistance and could partially explain the association between PsA and DM. Moreover, adiponectin and omentin, with insulin-sensitizing and anti-atherogenic properties, are decreased in patients with PsA. Some of the treatments for PsA could affect the glucose homeostasis. Systemic corticosteroids are known to impair insulin resistance, whereas apremilast (phosphodiesterase type 4 inhibitor) and TNF-α inhibitors could exert neutral effect or reduce the insulin-resistance. The role of IL-17 or IL-23 inhibitors has been marginally investigated. CONCLUSIONS: Patients affected by PsA have a higher prevalence of type 2 DM compared with the general population. The mechanism linking PsA with DM has not been completely clarified, but some of the principal mediators could be TNF-α and adipokine, especially adiponectin and omentin. Apremilast and TNF-α inhibitor may have a favorable effect and could be safely used in patients with DM.

Long-term Survival of Patients With Invasive Ultra-thin Cutaneous Melanoma: A Single-center Retrospective Analysis.

The incidence of cutaneous melanoma is increasing worldwide, especially for thin melanoma (Breslow ≤1 mm). Thin cutaneous melanoma has a favorable prognosis but there are few data about the prognosis of patients with ultra-thin cutaneous melanoma (Breslow ≤ 0.5 mm). Our aim was to investigate the disease-free survival among patients with invasive cutaneous melanoma with Breslow ≤ 0.5 mm after 10 years from the initial diagnosis.A retrospective review of 240 cutaneous melanoma patients with Breslow ≤ 0.5 mm was performed. Recurrence, death from cutaneous melanoma, and disease-free survival were all identified.In the whole group of patients, we observed only 2 deaths from cutaneous melanoma. Median follow-up was 13, 11 years. Among all 240 patients, 221 were alive and disease free, 2 died of cutaneous melanoma, 11 died of other non-neoplastic diseases, 5 died of other neoplastic diseases different from melanoma, and 1 patient had a local recurrence; therefore the 10-year melanoma survival rate was 99.6%.Our data indicate that death from cutaneous melanoma in the group of patients with Breslow ≤0.5 mm was a very rare event and that diagnosis at this stage dramatically decreases the risk of developing metastatic tumors to a <0.5% also after a 10-year period of follow-up. Limitation of the study includes the fact that other risk factors for melanoma, notably ulceration, and mitotic rate, were not evaluated.