Real-world use of ustekinumab therapeutic drug monitoring in moderate to severe psoriasis.

Introduction: There is growing evidence that therapeutic drug monitoring of biologic therapy is beneficial in psoriatic patients. With respect to ustekinumab, the available evidence has not shown any relationship yet. The objective of this study is to identify correlations among ustekinumab trough concentrations, anti-ustekinumab antibodies and clinical response in moderate-to-severe plaque psoriasis patients, in a real-world setting. Methods: Observational prospective follow-up study in psoriatic patients treated with ustekinumab. Patients were classified in optimal (PASI ≤ 3) and suboptimal responders (PASI > 3). Mann-Whitney U test and Spearman's rank correlation coefficient were used. Receiver-operator characteristic curve analysis was performed to identify ustekinumab concentration cut-off to achieve optimal response. A p-value < 0.05 was considered statistically significant. Results: A total of 59 patients were included. Forty-eight patients (81.4%) corresponded to optimal responders and 11 (18.6%) to suboptimal responders. There was significant difference to ustekinumab concentrations: 0.7 µg/mL (range <0.1-1.8) vs. 0.4 µg/mL (range <0.1-0.8) respectively (p = 0.007). Positive correlation between ustekinumab concentration and psoriasis area and severity index (PASI) value was detected (p = 0.009). A cut-off value of 0.6 µg/mL ustekinumab concentration was found to achieve clinical response. Anti-ustekinumab antibodies were detected in 2 (3.4%) samples, both suboptimal responders. Conclusion: A positive correlation exits between ustekinumab concentration and clinical response (optimal response PASI values ≤ 3) in blood draws performed before drug administration. The measurement of anti-ustekinumab antibodies could be considered in treatment failure.

Biologic Therapy for Moderate to Severe Psoriasis. Real-World Follow-up of Patients Who Initiated Biologic Therapy at Least 10 Years Ago.

INTRODUCTION: The aim of this study was to evaluate response and drug survival of biologic therapy in patients with moderate to severe plaque-type psoriasis who initiated biologic therapy at least 10 years ago, in a real-world setting. METHODS: This was an observational retrospective follow-up study that included patients with moderate to severe plaque-type psoriasis who initiated biologic therapy between October 2006 and December 2009. Efficacy was expressed as the percentage of patients achieving a 50, 75 and 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI 50, PASI 75, PASI 90, respectively) every 3 months during the first year of therapy and then every 12 months up to the end of follow-up or withdrawal from the study. RESULTS: A total of 56 patients were included in the study, representing 140 treatment lines (median 2, range 1-8); of these patients, 53 were still receiving biologic therapy at the end of the study. The mean duration of biologic therapy was 140.4 (range 47.6-175.4) months. Etanercept was used in 98.2% of patients, followed by efalizumab (42.9%), adalimumab (41.1%), ustekinumab (33.9%) and infliximab (16.1%). Treatment lines were switched in 62.1% of treatments: 24.3% due to secondary failure, 20.7% due to primary failure and 3.6% due to side effects. No patient treated with anti-interleukins had to discontinue treatment due to side effects. Ustekinumab had the highest drug survival. CONCLUSIONS: This study in the real-world-setting shows maintenance of long-term efficacy and safety of biologic therapy in patients with moderate to severe plaque psoriasis in daily practice who initiated biologic therapy 10 years ago.

Positive correlation between etanercept concentration and the decrease in Psoriasis Area and Severity Index scale value.

Background In the case of psoriatic patients, only a limited number of studies have related serum biological therapies and antidrug antibodies levels to clinical response. With respect to etanercept, the available evidence has not shown any relationship yet. Objective The aim of this study was to determine if there is any correlation among etanercept serum levels, the presence of anti-etanercept antibodies and clinical response to this treatment in psoriatic patients. Setting A 1500-bed hospital (A Coruña University Hospital Complex). Method A retrospective observational study in psoriatic patients treated with etanercept (50 mg once weekly) was carried out. Psoriasis Area and Severity Index scale and adverse reactions were recorded at the time of the extraction sample. The pharmacokinetic monitoring was evaluated at the previous time points by extracting peripheral blood samples before the dose administration. Etanercept and anti-etanercept antibodies concentrations were quantified by two sandwich-type ELISA immunoassays. The patients were classified into three groups (good, partial and nonresponders) in accordance with the treatment efficacy at the blood assessment moments. The Kruskall-Wallis test and Spearman correlation assay were used to assess the efficacy and incidence of adverse effects according to the etanercept concentration and anti-etanercept antibodies, considering p values of <0.05 as statistically significant. This statistical analysis was conducted using SPSS software (version19.0). Main outcome measures Etanercept and anti-etanercept antibodies trough serum levels and clinical response. Results 38 patients were included. 26 patients (68.4 %) were good, 5 (13.2 %) were partial and 7 (18.4 %) were non-responders. There was no significant difference with respect to etanercept levels: 2.7 µg/mL (range 0.7-5.6) versus 2.2 µg/mL (range 1.0-3.5) versus 1.73 µg/mL (range 0.1-2.3), respectively (p = 0.085). Nevertheless, a positive correlation between percentage decrease in the Psoriasis Area and Severity Index scale value with respect to the baseline value and etanercept concentration was found (p = 0.011). No anti-etanercept antibodies were detected; nor was there a significant difference in the incidence of adverse effects (p = 0.8523). Conclusions Our results showed a positive correlated between etanercept concentration and the percentage decrease in the Psoriasis Area and Severity Index scale value. The incidence of anti-etanercept antibodies in psoriatic patients was low.

Long-Term Efficacy of Etanercept for Plaque-Type Psoriasis and Estimated Cost in Daily Clinical Practice.

BACKGROUND: There are numerous clinical trials proving efficacy and safety profiles of etanercept. Newer studies, however, include patients with significant comorbidities, unstable psoriasis, or concomitant treatments. OBJECTIVE: The objective of this study was to provide data on long-term response to etanercept and estimate the cost in daily practice. METHODS: This is an observational retrospective study including patients with plaque-type psoriasis receiving etanercept 50 mg/wk for more than 6 months at the Dermatology Department of the University Hospital of La Coruña (Spain). Psoriasis severity was determined using the Psoriasis Area and Severity Index (PASI) at baseline and then at 12 weeks, 24 weeks, and annually until treatment discontinuation. RESULTS: A total of 102 patients aged 24 to 78 years were included. Response rates of 58.8% and 66.3% for PASI 75 score (reduction of at least 75% in PASI score compared with baseline) were achieved after 12 and 24 weeks of treatment, respectively. Among patients who continued treatment, the PASI 75 score was maintained by 75.3% at 1 year, 82.5% at 2 years, and 88.2% at 3 years. The percentage of patients receiving other systemic treatments was 38.2%. Adverse effects were reported in 13.7%, all of them mild, except one case of urinary sepsis. The average cost per patient was €244.68 ± €45.27 per week and €34.95 ± €6.46 per day. CONCLUSIONS: We provide data on long-term response to etanercept and its costs in a real-world setting. Response rates were higher than in some clinical trials, with progressive efficacy and not related to body mass index. Etanercept cost was comparable with that estimated in other studies. Combination with a conventional systemic agent can enhance efficacy without additional adverse events.

Teledermatology: diagnostic reliability in 383 children.

BACKGROUND: There are few studies of teledermatology focused on the pediatric age group. The aim of this study was to assess the validity and reliability of store-and-forward teledermatology (STD) as a diagnostic tool for pediatricians and to reduce face-to-face consultations. MATERIAL AND METHODS: A retrospective, observational study of 383 children and adolescents under 15 years of age, referred from primary care to Dermatology Department of University Hospital of La Coruña, Spain, between 2011 and 2013, using a STD consult system. RESULTS: Diagnoses concordance between pediatricians and teledermatologists was 39.2% of cases and partial concordance 16.7%. Agreement for global diagnosis was κ = 0.78 (p = 0.000) and for specific diagnosis was κ = 0.73 (p = 0.000). Management was concordant in 28.7% and partially concordant in 15.4%. Lower reliability was statistically associated with modification of the lesions by inappropriate treatments, incomplete clinical data or bad-quality photographic images included in the referral consultation, diagnosis of infectious diseases and rare dermatoses. The filtering percentage (as the percentage of avoided clinic-based evaluations) was 64.5%. The mean response time of the consultant dermatologists was 3.62 days. Referrals for live consultations due to poor clinical information or insufficient quality of pictures were necessary in only 10% of the cases. CONCLUSION: The degree of diagnostic accuracy for the pediatric population using STD as a diagnostic tool was similar to that achieved in adults. Its usefulness for filtering dermatologic referral was also demonstrated in the study, so it could be suitable for integration into the routine practice of pediatricians.

Efficacy and safety of adalimumab in psoriatic patients previously treated with etanercept in a real-world setting.

INTRODUCTION: Knowledge on the efficacy and safety of adalimumab in psoriasis patients switching from etanercept is scarce, especially on the influence that causes of etanercept discontinuation may have on adalimumab response. OBJECTIVES: To evaluate the response, adverse effects and factors that may influence the efficacy and safety of adalimumab in psoriasis patients who failed on etanercept therapy in a real-world setting. METHODS: Data from all moderate to severe plaque psoriasis patients who switched from etanercept to adalimumab were extracted from a registry of biological therapies of our department. Primary endpoint was the percentage of patients achieving PASI 50 at weeks 12, 24, and 52. Secondary endpoints were the percentages of patients achieving PASI 75 and PASI 90, patients who maintained PASI values <5 and <3, and the safety of adalimumab. RESULTS: Of 35 patients who fulfilled the study criteria, 82.9% achieved PASI 50 at week 12, 74.3% at week 24, and 74.3% at week 52 on adalimumab treatment. Eleven of 16 primary and 11 of 17 secondary nonresponders to etanercept responded to adalimumab. There were no treatment discontinuations due to side effects. CONCLUSIONS: Previous etanercept failure seems not influence the success and safety of adalimumab treatment in moderate to severe plaque psoriasis.

Quality of life and related factors in a cohort of plaque-type psoriasis patients in La Coruña, Spain.

BACKGROUND: Psoriasis can significantly affect the physical, psychological, and social aspects of a patient's life. Many studies have evaluated the effects of psoriasis on quality of life (QoL), but results in many cases are contradictory. OBJECTIVES: This study was conducted to assess the relationships between the characteristics of psoriasis (cutaneous severity, arthropathy, treatment) and comorbidities with QoL and to determine which factors have a major influence. METHODS: We assessed demographic data, the severity of cutaneous involvement, psoriasis treatment, presence of arthropathy, psoriasis duration, smoking status, alcohol intake, and the presence of comorbidities. Concomitant diseases were evaluated using the Charlson Comorbidity Index and the National Cholesterol Education Program Adult Treatment Panel III (ATP-III) criteria for metabolic syndrome. Quality of life was assessed using the Dermatology Life Quality Index (DLQI). RESULTS: Multivariate analysis showed that factors associated with QoL impairment included gender (women experienced greater impact: odds ratio [OR] 2.85, 95% confidence interval [CI] 1.48-5.49; P = 0.002); psoriasis duration (patients with longer durations of psoriasis and psoriasis treatment experienced less impairment: OR 0.96, 95% CI 0.94-0.99; P = 0.004); and treatment type (impact was lower in patients receiving biologic drugs than in those using topical treatment [OR 3.15, 95% CI 1.50-6.62; P = 0.002] and in those using biologics compared with those using conventional systemic treatment [OR 2.23, 95% CI 0.98-5.05; P = 0.053]). Psoriasis severity measured according to scores on the Psoriasis Area and Severity Index (PASI) and body surface area affected was not related to QoL impairment. Comorbidities were associated with impaired QoL in the univariate analysis but not after adjusting for other covariates. CONCLUSIONS: Factors associated with greater impairment of QoL were gender, psoriasis duration, and type of treatment. Patients receiving systemic and biologic therapies reported better QoL.

Subcutaneous histiocytoid sweet syndrome associated with crohn disease in an adolescent.

We report a case of subcutaneous histiocytoid Sweet syndrome in an adolescent with Crohn disease. A 14-year-old boy with a 1-year history of ileocolonic and perianal Crohn disease, treated with infliximab and azathioprine, was admitted to the Pediatrics Department with malaise, abdominal pain, bloody diarrhea, and fever (39°C) from 15 days ago. Two days later, he developed cutaneous lesions consisting of tender, erythematous, and violaceous papules and nodules scattered over his legs, soles, and upper extremities. Laboratory studies revealed neutrophilia, microcytic anemia, and elevation of both erythrocyte sedimentation rate and C-reactive protein rate. A skin biopsy specimen showed deep dermal and predominantly septal inflammatory infiltrate in the subcutaneous tissue composed of polymorphonuclears, eosinophils, and mononuclear cells of histiocytic appearance. These histiocytoid cells stained positive for myeloperoxidase. Subcutaneous Sweet syndrome is a rare subtype of acute neutrophilic dermatosis, in which the infiltrate is exclusively or predominantly located in the subcutaneous tissue, causing lobular or septal panniculitis. It is often described in patients with an underlying haematological disorder or caused by drugs, but very rare in patients with inflammatory bowel disease, especially in childhood or adolescence. To our knowledge, this is the first case of subcutaneous histiocytoid type in a paediatric patient.

Long-term response to etanercept monotherapy in moderate to severe psoriasis: assessment in daily practice by the maintenance of low values of PASI and BSA.

INTRODUCTION: Efficacy and safety profiles of etanercept have been proved in numerous clinical trials; however, efficacy is determined by means of PASI 75 and few studies consider the maintenance of long-term response. The aims of this study were to provide data on long-term response to etanercept monotherapy in daily practice and to propose a method to assess the efficacy based on the maintenance of low PASI and BSA. METHODS: Patients with moderate-severe psoriasis treated with etanercept 50 mg weekly, achieving at least PASI 50 at 12 weeks, were included. Response was expressed as the percentage of patients maintaining PASI and BSA ≤5 and ≤3, respectively. RESULTS: We included 76 patients (73.7% male and 26.3% female). PASI remained ≤5 in 71.1%, 61.3%, 54.4%, 38.3%, 8.6% and 5.9% of patients and ≤3 in 51.3%, 46.8%, 42.1%, 34%, 8.6% and 5.9% at 3, 12, 18, 24, 36 and 42 months. CONCLUSIONS: The maximum response is achieved between 6 and 9 months and remains stable in about 50% of cases until 18-24 months. Response maintains beyond 42 months in 6%. Maintenance of low PASI and BSA may be a most useful measure than the initial PASI reduction, which not always means enough improvement for the patient.

Long-term efficacy of infliximab in hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic disease with painful, inflamed lesions in the apocrine gland-bearing areas of the body and unsatisfactory treatment. TNFα blockers have been proposed as promising treatments, but only few randomized, short-term, small controlled trials have been conducted. The aim of this study was to evaluate long-term response of HS patients treated with infliximab (IFX). MATERIAL AND METHODS: A long-term, prospective study of 10 patients with moderate-severe refractory HS treated with IFX was performed, including assessment of therapy safety, disease severity, and activity. Previous reports on IFX treatment for HS were reviewed. RESULTS: Lack of response was observed in 20% and relapse in 50% of patients, after a median period of 37 weeks. The median number of doses administered was 7.5 during 49 weeks. No life-threatening adverse events were detected. Systematic review of 61 previously published cases showed lack of response was associated with previous surgery, young age at diagnosis, and long time of evolution of the disease. CONCLUSIONS: Long-term IFX therapy might be an efficient, well-tolerated, safe option for patients with short-time evolution, severe HS. Relapse is common after 8 months of continuous treatment, especially in patients with more severe disease and in those treated with IFX in monotherapy.

Infliximab-induced lichen planopilaris.

OBJECTIVE: To report a case of lichen planopilaris in a patient treated with infliximab for longstanding refractory psoriasis. CASE SUMMARY: A 37-year-old man with recalcitrant plaque psoriasis was being treated with infliximab at a dosage of 5 mg/kg every 8 weeks, with good response. However, 11 months later the patient developed follicular keratotic papulo-pustules, perifollicular erythema, and scaling, with progressive hair loss of the frontal and parietal regions of the scalp and eyebrows. A skin biopsy from a representative lesion was consistent with the diagnosis of lichen planopilaris. DISCUSSION: Anti-tumor necrosis factor (TNF) agents have been associated with numerous cutaneous adverse events. Lichenoid reactions are uncommon but are an emerging cutaneous adverse effect. At least 13 cases of these eruptions have been recently described. Although lichenoid reactions in patients treated with TNF-alpha inhibitors may be clinically very diverse, we have found no previously reported cases of lichen planopilaris induced by these agents. An objective causality assessment revealed that the adverse event was probable. CONCLUSIONS: Since anti-TNF agents are being used for a rapidly expanding number of rheumatic, digestive, and dermatologic diseases, it is expected that lichenoid eruptions and other skin toxicities are likely to be seen with increasing frequency in clinical practice.

Venous malformations with lip involvement: palliative treatment with carbon dioxide laser vaporization in five cases.

BACKGROUND: The treatment of venous malformations remains controversial. Traditional surgical excision is only possible in a few cases. Numerous sclerosing agents have been used, but none of them are ideal or absolutely safe for the treatment of venous disorders. In isolated cases, an expectative control would be a good option. OBJECTIVE: To report our experience with CO(2) laser vaporization as palliative treatment in five cases of head and neck venous malformations with lip involvement. METHODS: Five patients were treated with a CO(2) laser in superpulsed, focused mode at 2 W/cm(2), with several passes in each session. Patients were aged from 16 to 49 years old (mean: 36.6 years). Three sessions of treatment were performed in two patients while only one session was used in the rest. The follow-up was 6-36 months (mean: 22.8 months). RESULTS: Significant cosmetic improvement with flattening of the lip surface was achieved in all patients. CONCLUSION: Carbon dioxide laser vaporization can be considered as one method of choice for an effective palliative treatment of lip involvement in venous malformations.