Fast and sustained improvement of patient-reported outcomes in psoriatic patients treated with secukinumab in a daily practice setting.

Psoriasis is a chronic dermatological disease with great impact on patients' quality of life (QoL). The main objective of this study was to assess the impact of secukinumab treatment on different patient-reported outcomes (PROs) during a long-term follow-up in Spanish patients with moderate-to-severe psoriasis under real-world conditions. Retrospective, observational, open-label, nationwide multicenter cohort study that included patients who initiated treatment with secukinumab in daily clinical practice conditions. PROs assessing disease impact and QoL included Dermatology Life Quality Index (DLQI), Patient's Global Psoriasis Assessment, Itch Numerical Rating Scale and EuroQoL Thermometer Visual Analogue Scale. Outcomes, including PROs and Psoriasis Area and Severity Index (PASI), were assessed at months 3, 6, 12, 18, and 24 during treatment. A total of 238 patients were enrolled in the study. Patients had a mean DLQI score of 14.9 at baseline; 78.3%, 73.7%, and 71.7% of them achieved a DLQI 0/1 response at months 6, 12, and 24, respectively. DLQI score was lower in the long term for naïve patients. A sharp decrease in mean DLQI was observed during the first 3 months, reaching a plateau that was maintained until the end of follow-up. Similar findings were observed for the rest of QoL assessments. There was a close association between improvement in QoL and skin clearance (PASI), which progressively increased during follow-up. In this study, secukinumab sustainably improved patient's QoL during a 24-month follow-up, with strongest effects in patients naïve to biological therapies and with a direct correlation with PASI improvement.

Secukinumab is effective and safe in the long-term treatment of plaque psoriasis in a daily practice setting: Multicenter study in 384 Spanish patients.

The aim of the study was to assess the long-term effectiveness and safety of secukinumab in Spanish patients with moderate-to-severe psoriasis in a daily practice setting. Nationwide multicenter, observational, retrospective, non-interventional, single-cohort study including patients who initiated treatment with secukinumab in daily clinical practice conditions. Subjects were followed for a minimum of 3 months and a maximum of 24 months. Psoriasis Area Severity Index (PASI), Body Surface Area and Physician's Global Assessments were collected at baseline and months 3, 6, 12, 18 and 24 during treatment. Adverse events and reasons for secukinumab withdrawal were collected and classified for analyses. A total of 384 patients were enrolled in the study. Median PASI declined rapidly from 14.3 at baseline to 2.7 at month 3, 2.1 at month 12, and remained low (2.8) at month 24. Within the group of patients with PASI ≥10 at baseline (n = 278), 58.3%, 60.4% and 56.5% achieved a PASI90 response at months 3, 12 and 24, respectively. As for absolute PASI, 86.5%, 69.5%, 42.7% and 37% achieved PASI <5, < 3, < 1 and 0, respectively, at month 3. Secukinumab was more effective in biologic-naïve patients and in those with lower Body Mass Index. Secukinumab presented a good long-term safety profile. Secukinumab was effective and safe in a routine clinical setting, in a large cohort of patients with moderate-to-severe plaque psoriasis, in the short-, medium- and long-term (up to 24 months).

Successful treatment of recalcitrant discoid lupus erythematosus with ustekinumab.

We report a 52-year old woman with a 28-year historyof disfiguring facial discoid lupus erythematosus(DLE), persistent despite both classical therapiesand rituximab. Ustekinumab 45 mg was started incombination with methotrexate and intralesionalcorticosteroids. Methotrexate and intralesionalcorticosteroids were withdrawn 30 months later andustekinumab maintained as monotherapy. Fortyeight months later stable improvement was achievedwithout side effects. Only nine patients with cutaneouslupus erythematosus (CLE) treated with ustekinumabhave been reported to date. Ustekinumab could be apromising alternative in severe and recalcitrant casesof CLE. Possibly, the Th17-inflammation pathway isplaying a role in these patients.

Dose reduction is a feasible strategy in patients with plaque psoriasis who achieve sustained response with secukinumab: a retrospective, multicenter cohort study in daily practice setting.

BACKGROUND: Biological therapy dose modification is a common practice in the long-term treatment of plaque psoriasis. OBJECTIVE: The objective of the study was to determine prevalence, characteristics of patients, effectiveness, treatment survival of secukinumab dose reduction (SEC-DR) strategy and assess its safety and cost implications. METHODS: A retrospective, observational, multicenter cohort study was conducted in patients with plaque psoriasis treated with secukinumab and up to 2 years of follow-up. RESULTS: In 63/347 patients with an initial standard dose regimen, SEC-DR was tried at any moment in 18.2% of them after sustained response. In 51 patients, the interval between administrations was increased while in 12 patients, monthly dose was reduced to 150 mg. Successful SEC-DR was achieved in 77.8% of the patients, with sustained PASI response to the end of the study. Survival of secukinumab treatment and safety profile were not compromised by DR. The use of DR saved 33% of the cost, including failures in which standard treatment was resumed. LIMITATIONS: The proper of the study designed and the arbitrary definition of "DR success." CONCLUSION: Off-label SEC-DR strategy was used in patients with sustained response to standard dose regimen; this strategy showed long-term efficacy without compromising treatment survival or worsening the safety profile while also being cost saving.

Photodynamic therapy for the treatment of folliculitis decalvans.

Folliculitis decalvans is a chronic form of deep folliculitis that occurs on the scalp as patches of scarring alopecia at the expanding margins of which are follicular pustules. Treatment of folliculitis decalvans is extremely difficult with a resultant poor prognosis. Photodynamic therapy has been reported to be effective in disorders as acne or folliculitis. We report one patient with folliculitis decalvans who was successfully treated with photodynamic therapy.

Cutaneous leishmaniasis with histopathologic pattern of non-necrotizing granulomatous dermatitis in patients treated with adalimumab.

Human leishmaniasis produced by Leishmania infantum is endemic in Mediterranean countries. In the context of a leishmaniasis outbreak in the town of Fuenlabrada, Madrid, Spain, we had two patients with cutaneous leishmaniasis that developed non-necrotizing cutaneous granulomas. They had both been receiving anti-TNF treatment with adalimumab for rheumatic diseases. Neither of them developed visceral disease and did not require anti-TNF treatment withdrawal to control the cutaneous disease. It is well known that anti-TNF therapy is associated with opportunistic diseases, especially with those in which granuloma formation is an important part of the host defence, as in tuberculosis. We think that granuloma formation through activation of Toll-like receptor-9 and via induction of a Th17 response may be precipitated by the parasites in the dermis.

Multicenter Retrospective Study of Secukinumab Drug Survival in Psoriasis Patients in a Daily Practice Setting: A Long-Term Experience in Spain.

INTRODUCTION: There is limited and conflicting evidence over the real-world drug survival of secukinumab (SEC) in patients with psoriasis, especially in the long term. Our objective was to analyze the short- and long-term survival of SEC (S-SEC) and its predictive factors for the treatment of psoriasis. METHODS:  Patients clinically diagnosed with plaque psoriasis and under treatment with secukinumab (n = 384) in a daily practice setting were analyzed in a retrospective, multicenter study performed in a nationwide cohort and followed up for a period of 2 years. Kaplan-Meier curve was plotted to analyze drug survival time, and log-rank test was performed to compare several groups. Factors related to speed of treatment discontinuation were studied with a Cox regression model. RESULTS: The overall cumulative secukinumab drug survival rates observed at 6, 12, 18, and 24 months were 97.1%, 89.0%, 81.1%, and 74.3%, respectively. Obesity [hazard ratio (HR), 1.809, CI 95% 1.114-2.962; p = 0.004] and previous experience with biological therapies, particularly those who had been treated with ≥ 2 biologicals with different mechanisms of action (HR 3.476, CI 95% 1.875-6.444; p = 0.017) were associated with an early discontinuation, whereas psoriatic arthritis was associated with delayed discontinuation, (HR 0.493, CI 95% 0.265-0.917; p = 0.025). CONCLUSIONS: In our study, we found that cumulative secukinumab drug survival for psoriasis patients for the period 6-18 months was in the range of real-world evidence studies. Additionally, we observed a relatively high long-term survival rate at 24 months (74.3%).

Unsuccessful treatment of recalcitrant cutaneous discoid lupus erythematosus with photodynamic therapy.

Discoid lupus erythematosus (DLE) can be a therapeutic challenge. Antimalarials and topic steroids are the first-line standard therapies, while systemic steroids, immunomodulators (as azathioprine, methotrexate, cyclosporine), retinoids (acitretin), thalidomide, auranofin and dapsone are used as second-line therapies. We report two patients with recalcitrant DLE who were treated with three and two sessions of 5-aminolevulinic photodynamic therapy without an improvement and with a bad tolerance to the therapy.

Long-term management of erythrodermic psoriasis with anti-TNF agents.

Erythrodermic psoriasis is a chronic condition that is difficult to treat. Biological agents offer a new alternative, but there are no controlled trials to support their use; there are a few reports of patients treated with these agents, but often only with short term results. We report a 68-year-old man with erythrodermic psoriasis and ankylosing spondylitis, treated with infliximab for 48 weeks and then low-dose etanercept monotherapy for 34 additional months. Excellent results were obtained for both conditions without significant side effects. We think etanercept can be a good therapeutic option for long-term control of erythrodermic psoriasis.

Current Insights Into The Management Of Discoid Lupus Erythematosus.

Discoid lupus erythematosus is the most disfiguring and common presentation of chronic cutaneous lupus erythematosus. Although most patients will respond to lifestyle measures and topical treatment, a non-negligible number of patients will require systemic and physical therapy, either alone or in combination. We performed a review of the available evidence on the discoid lupus erythematosus treatment. Lifestyle measures and topical treatment (corticosteroids and topical calcineurin inhibitors) remain the therapeutic strategies with the highest evidence level. Within systemic treatment approaches, antimalarial drugs are still the first-line therapy, while other systemic and physical therapies have highly variable evidence. Hence, we propose a therapeutic algorithm based on the strength of recommendations of the different treatment modalities, focusing on the refractory disease.

Lipschütz [corrected] ulcers--four cases.

A distinctive clinical entity of acute genital ulcers occurring in adolescents, with nonvenereal infectious etiology was described by Lipschütz in 1913. We describe four puberal virgin girls who developed fever and painful genital ulcers. The main causes infectious and noninfectious of ulceration were rejected. Although the etiology is unknown, recent cases related with Epstein-Barr virus acute infection have been reported.

Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease.

Increased numbers of peripheral blood mononucleocytes (PBMC) and increased IFN-γ secretion following in vitro challenge of blood samples with soluble Leishmania antigen (SLA), have been proposed as biomarkers of specific cell-mediated immunity, indicating that treatment of visceral leishmaniasis (VL) has been successful. However, Leishmania infantum infection may manifest as cutaneous leishmaniasis (CL), and less commonly as localized leishmanial lymphadenopathy (LLL) or mucosal leishmaniasis (ML). The present work examines the value of these biomarkers as indicators of cured leishmaniasis presenting in these different forms. Blood samples were collected before and after treatment from patients living in Fuenlabrada (Madrid, Spain), an L. infantum-endemic area recently the center of a leishmaniasis outbreak. All samples were subjected to Leishmania-specific PCR, serological tests (IFAT and rK39-ICT), and the SLA-cell proliferation assay (SLA-CPA), recording PBMC proliferation and the associated changes in IFN-γ production. Differences in the results recorded for the active and cured conditions were only significant for VL. PCR returned positive results in 67% of patients with active VL and in 3% of those with cured leishmaniasis. Similarly, rK39-ICT returned a positive result in 77% of active VL samples vs. 52% in cured VL samples, and IFAT in 90% vs. 56%; in the SLA-CPA, PBMC proliferation was seen in 16% vs. 90%, and an associated increase in IFN-γ production of 14 and 84%, respectively. The present findings reinforce the idea that PBMC proliferation and increased IFN-γ production in SLA-stimulated PBMC provide biomarkers of clinical cure in VL. Other tests are urgently needed to distinguish between the cured and active forms of the other types of clinical leishmaniasis caused by L. infantum.

Efficacy and safety of etanercept in psoriasis/psoriatic arthritis: an updated review.

The introduction in recent years of biologic medicines has greatly changed the treatment of psoriasis and psoriatic arthropathy (PsA). These drugs have been effective in the treatment of these chronic, physically weakening disorders, offering good efficacy and a safety profile that differs from those of all other systemic therapies and medications available to date. Different studies have assessed the efficacy and safety of etanercept in the treatment of psoriasis and PsA. Etanercept therapy for up to 144 weeks in psoriasis has shown maintenance of efficacy over time, recapture of initial clinical responses in patients who interrupted their etanercept therapy and were re-treated, an increased percentage of clinical responses in medium-dose non-responding patients who switched to higher dosages, good responses on quality-of-life tests, and an adverse event-adjusted rate similar to placebo. In PsA, etanercept therapy for up to 96 weeks was associated with inhibition of radiologic progression of the disease in addition to maintenance of efficacy over time and good responses on quality-of-life tests. In studies of patients with psoriasis, the adverse effects of etanercept were mostly mild, did not require discontinuation of treatment, and were not associated with cumulative toxicity over time. However, safety concerns about etanercept therapy are well known, and include injection-site reactions, infections, congestive heart failure, demyelinating diseases, lupus-like syndromes, and neoplasms. There are no data about any new safety concerns when etanercept is combined with systemic traditional therapies, although use of this therapy has been reported in only a small number of patients to date.Non-neutralizing anti-etanercept antibodies are not related to a decreased response to therapy and neutralizing antibodies have not been described to date. Treatment of patients infected with hepatitis C virus or HIV does not increase viral load in either case, affect liver function tests, or increase the risk of infections. To date, the available data suggest that use of etanercept during pregnancy or in breast-feeding women should be avoided. Children and the elderly may be treated with similar efficacy and safety profiles as have been observed in adults. Non-live vaccines can be administered to patients taking etanercept. Because of its long-term efficacy and safety, etanercept is likely to become a treatment option for consideration in the long-term management of patients with psoriasis and PsA.