Marta Ferran

Risk of Serious Adverse Events Associated With Biologic and Nonbiologic Psoriasis Systemic Therapy: Patients Ineligible vs Eligible for Randomized Controlled Trials

OBJECTIVE To describe the use of systemic therapy for psoriasis (biologic and nonbiologic [classic] drugs) in patients not adequately represented in randomized controlled trials (RCTs) and the risk of serious adverse events (SAEs) in these patients. DESIGN A registry inception cohort was used. SETTING Thirteen dermatology departments in Spain participated. PATIENTS A consecutive sample of patients treated with biologics and a systematic sample of patients treated with classic systemic therapy were evaluated. A total of 1042 patients (2179 person-years) were included. EXPOSURE Inadequate representation in trials was defined as the presence of any of the following factors: elderly age (>70 years); type of psoriasis other than chronic plaque psoriasis; history of infection caused by hepatitis B, hepatitis C, or human immunodeficiency virus; history of cancer (excluding nonmelanoma skin cancer); and chronic renal or hepatic disease. MAIN OUTCOME MEASURES Serious adverse events as defined by the International Conference on Harmonization were evaluated. RESULTS In all, 29.8% of patients receiving systemic therapy for psoriasis would not have been eligible for RCTs. These individuals had an increased risk of SAEs (incidence rate ratio, 2.7; 95% CI, 1.5-4.7). Patients exposed to biologics had an adjusted increased risk of SAEs (incidence rate ratio, 2.3; 95% CI, 1.1-4.8) that was similar in patients eligible and ineligible for RCTs. CONCLUSIONS Patients ineligible for RCTs are an important proportion (30%) of those receiving systemic therapy for psoriasis. These patients have a higher risk of SAEs and should be closely monitored. Patients exposed to biologics (whether these patients are eligible for RCTs or ineligible) are susceptible to the same increase in risk of SAEs, but biologics add to a higher baseline risk in patients who are ineligible for RCTs. The risk-benefit ratio in ineligible patients receiving biologics might be different from the ratio in eligible patients.

Rupatadine and its effects on symptom control, stimulation time, and temperature thresholds in patients with acquired cold urticaria

BACKGROUND Patients with acquired cold urticaria (ACU) show itchy wheals during cold exposure. This disturbing condition involves histamine and platelet-activating factor in its pathogenesis. Rupatadine is a dual antagonist of both histamine and platelet-activating factor. OBJECTIVE To assess rupatadine efficacy in preventing reactions to cold challenge in patients with ACU. METHODS A crossover, randomized, double-blind, placebo-controlled study in which 21 patients with ACU received rupatadine, 20 mg/d, or placebo for 1 week each is presented. The main outcome was the critical stimulation time threshold (CSTT) determined by ice cube challenge. Secondary outcomes included CSTT and the critical temperature threshold assessed by a cold provocation device (TempTest 3.0), as well as scores for wheal reactions, pruritus, burning sensations, and subjective complaints after cold challenge. RESULTS After rupatadine treatment, 11 (52%) of 21 patients exhibited a complete response (ie, no urticaria lesions after ice cube provocation). A significant improvement in CSTT compared with placebo was observed after ice cube and TempTest 3.0 challenge (P = .03 and P = .004, respectively). A significant reduction of critical temperature threshold (P < .001) and reduced scores for cold provocation-induced wheal reactions (P = .01), pruritus (P = .005), burning sensation (P = .03), and subjective complaints (P = .03) after rupatadine treatment were also found. Mild fatigue (n = 4), somnolence (n = 1), and moderate headache (n = 1) were reported during active treatment. CONCLUSION Rupatadine, 20 mg/d, shows high efficacy and is well tolerated in the treatment of ACU symptoms.

Alopecia areata as another immune-mediated disease developed in patients treated with tumour necrosis factor-α blocker agents: Report of five cases and review of the literature.

Background  Tumour necrosis factor antagonists (anti‐TNF‐α) have demonstrated the efficacy in different chronic immune inflammatory disorders. Within the spectrum of adverse events, autoimmune diseases have been observed, including cases of alopecia areata (AA).

Risk of adverse events in psoriasis patients receiving classic systemic drugs and biologics in a 5-year observational study of clinical practice: 2008–2013 results of the Biobadaderm registry

Biobadaderm is the Spanish registry of psoriasis patients receiving systemic treatment in clinical practice.

Survival of classic and biological systemic drugs in psoriasis: results of the BIOBADADERM registry and critical analysis.

Few reported studies compare drug survival in moderate‐to‐severe psoriasis vulgaris.

Streptococcus induces circulating CLA(+) memory T-cell-dependent epidermal cell activation in psoriasis.

Streptococcal throat infection is associated with a specific variant of psoriasis and with HLA-Cw6 expression. In this study, activation of circulating psoriatic cutaneous lymphocyte-associated antigen (CLA)(+) memory T cells cultured together with epidermal cells occurred only when streptococcal throat extracts were added. This triggered the production of Th1, Th17, and Th22 cytokines, as well as epidermal cell mediators (CXCL8, CXCL9, CXCL10, and CXCL11). Streptococcal extracts (SEs) did not induce any activation with either CLA(-) cells or memory T cells cultured together with epidermal cells from healthy subjects. Intradermal injection of activated culture supernatants into mouse skin induced epidermal hyperplasia. SEs also induced activation when we used epidermal cells from nonlesional skin of psoriatic patients with CLA(+) memory T cells. Significant correlations were found between SE induced upregulation of mRNA expression for ifn-γ, il-17, il-22, ip-10, and serum level of antistreptolysin O in psoriatic patients. This study demonstrates the direct involvement of streptococcal infection in pathological mechanisms of psoriasis, such as IL-17 production and epidermal cell activation.

Clinical Characteristics and Psychopathological Profile of Patients with Vulvodynia: An Observational and Descriptive Study

Background: Vulvodynia is a fairly common dermatological symptom that often interferes with the personal, social and working activities of affected women and results in a significant loss of their quality of life. It is a persistent and tedious clinical disorder which is often resistant to conventional treatments. Objectives: The aim of this study is to evaluate the main clinical signs, associated psychopathological disorders and outcome after antidepressant treatment of patients with vulvodynia. Methods: Eighty patients were included. Clinical characteristics and psychopathological profiles were determined by appropriate instruments. The improvement of clinical symptoms after combined antidepressant drug therapy was also evaluated. Results: Pain (70%), burning (63.7%), dyspareunia (57.5%) and stinging (56.2%) were the most commonly reported symptoms. Most patients (56.5%) showed anxiety, and 52.2% of them were reported as having a depression disorder. When evaluated by psychometric tools, 81.4% of patients scored >150 on the Life Event Scale, which means a risk >50% of suffering an illness in the near future, and patients’ scores in the Dermatology Life Quality Index showed higher values than the mean of the Spanish validation group. After 6 months of combined treatment with escitalopram (10–20 mg/day), perfenazine (2–4 mg/day) and amytriptiline (10 mg/day), a complete remission of the clinical symptoms was achieved in 41% of patients. In contrast, only 12% of patients who did not follow drug treatment reported a complete resolution of the clinical symptoms. Conclusions: Our results seem to confirm that vulvodynia is associated with psychiatric co-morbidity such as stress and depression. The study highlights that the psychiatric treatment may be a useful option to improve clinical symptoms. Whether these patients should be evaluated for depression or be referred to a psychiatrist, remains to be investigated.

Safety of classic and biologic systemic therapies for the treatment of psoriasis in elderly: an observational study from national BIOBADADERM registry.

Psoriasis patients over 65 years‐old (elderly) constitute a growing group, underrepresented in clinical trials, and likely to be more prone to adverse events.

Circulating CLA+ T lymphocytes as peripheral cell biomarkers in T-cell-mediated skin diseases

T lymphocytes expressing the CLA antigen constitute a subset of effector memory lymphocytes that are functionally involved in T‐cell‐mediated cutaneous diseases. Skin‐seeking lymphocytes recirculate between inflamed skin and blood during cutaneous inflammation. Many studies in different T‐cell‐mediated inflammatory cutaneous diseases have clearly related their pathologic mechanisms to CLA+ T cells. Based on common features of these cells in different cutaneous disorders mediated by T cells, we propose that circulating CLA+T cells could constitute very useful peripheral cellular biomarkers for T‐cell‐mediated skin diseases.

Pathological mechanisms of skin homing T cells in atopic dermatitis.

Skin infiltration of circulating memory T cells with cutaneous tropism is considered one of the pathologic mechanisms in atopic dermatitis (AD). Skin-seeking circulating T lymphocytes can be identified by their expression of the cutaneous lymphocyte-associated antigen on the cell surface. Recent studies have contributed useful new information about the function and recirculation properties of those cells in AD patients. This review integrates the latest findings on peripheral cutaneous lymphocyte-associated antigen memory T cells in AD and highlights the relevance of this cell type and its importance to our understanding of the pathologic mechanisms of AD.