Reaching Treatment Goals in Psoriasis with Conventional Systemic Drugs: How Long Are We Willing to Wait?

OBJECTIVES: The purpose of this study was to investigate the attainment of treatment goals according to the European Consensus Programme (ECP-TGs) from 2011 in patients with moderate to severe psoriasis (Pso) treated with the first conventional systemic therapy and to identify factors that might compromise the attainment of these treatment goals. METHODS: In a multicenter, prospective observational study, patients with moderate to severe Pso, defined as either body surface area (BSA) >10% or psoriasis area severity index (PASI) >10 and dermatology life quality index (DLQI) >10, received a conventional systemic therapy that could be modified at each follow-up visit over the course of 18 months. All subjects signed an informed consent form, were ≥18 years of age as well as systemic therapy naïve, and had regular study visits at months 3, 6, 9, 12, and 18 after baseline. Among others and in addition to demographic and disease-related characteristics at baseline, we documented BSA, PASI, DLQI, and the physician-reported attainment of treatment goals at each follow-up visit. Factors related to a failure in achieving the ECP-TGs (i.e., either Δ PASI ≥75 or Δ PASI ≥50 and <75 with a DLQI ≤5) at month 18 were investigated by multiple logistic regression. Descriptive results are presented as the mean ± SD for interval data, and absolute as well as relative frequencies for nominal data. For this part of the analysis, data at baseline and months 6, 12, and 18 are presented. RESULTS: A total of 133 Pso patients with a mean age and disease duration of 49.5 ± 14.4 and 15.6 ± 12.8 years, respectively, were included in the analysis; 54.1% (n = 72) were male. The mean baseline disease-related outcomes were: BSA: 21.5 ± 15.8%, PASI: 13.7 ± 7.14, and DLQI: 12.0 ± 6.11. The most common conventional systemic therapies initiated at baseline were fumaric acid esters (n = 74, 55.6%), methotrexate (n = 46, 34,6%), and ciclosporin (n = 6, 4.5%). The ECP-TGs were achieved by 58 patients (43.6%) at month 6, 86 patients (64.7%) at month 12, and 97 patients (72.9%) at month 18. An optimized reduced logistic regression model identified the presence of onycholysis/nail dystrophy at two or more digits to be associated with failing to attain the ECP-TGs (OR 10.7, 95% CI 2.5-46.7, p = 0.002). CONCLUSION: Patients with onycholysis/nail dystrophy at two or more digits were identified as having a higher risk of not achieving ECP-TGs under conventional systemic therapy. The ECP-TGs from 2011 were attained by 43.6% of our patients 6 months after starting conventional systemic therapies. In the era of safe, fast, and efficacious Pso therapies, much higher treatment goals might be achieved during therapy. New treatment goals are only of use if patients and dermatologists strive to attain them.

Palmoplantar pustulosis - a cross-sectional analysis in Germany.

BACKGROUND: Palmoplantar pustulosis (PPP) is a recalcitrant chronic inflammatory skin disease. Data relevant for the medical care of patients with PPP are scarce. Thus, the aim of this work was to investigate the disease burden, clinical characteristics, and comorbidity of PPP patients in Germany. PATIENTS AND METHODS: PPP patients were examined in a crosssectional study at seven specialized psoriasis centers in Germany. RESULTS: Of the 172 included patients with PPP, 79.1% were female and 69.8% were smokers.In addition, 25.0% suffered from psoriasis vulgaris, 28.2% had documented psoriatic arthritis, and 30.2% had a family history of psoriasis. In 77 patients the mean Dermatology Life Quality Index (DLQI) was 12.2 ± 7.7 (mean ± SD). The mean Psoriasis Palmoplantar Pustulosis Area and Severity Index (PPPASI) was 12.6 ± 8.6. Mean body mass index was above average at 27.1 ± 5.5. The PPP patients had previously received an average of 2.6 ± 2.1 different anti-psoriatic systemic drugs or UV-therapies. The systemic drugs that had been used most frequently were corticosteroids in 40.1% of patients, followed by acitretin (37.8%), and methotrexate (27.9%). The PPPASI was 13.4 ± 8.9 in patients without current systemic therapy and 10.4 ± 7.9 in patients with systemic therapy. CONCLUSION: Many PPP patients had a concomitant diagnosis of psoriasis vulgaris and/or psoriatic arthritis or had a family history of psoriasis. Despite the fact that many of the patients were using anti-psoriatic therapies, there was still a high burden of disease within this PPP cohort. This insufficient control of symptoms demonstrates the urgent need for new PPP treatments.

Ustekinumab in the treatment of palmoplantar pustular psoriasis - a case series of nine patients.

BACKGROUND: Palmoplantar pustular psoriasis is a chronic inflammatory skin disease that is associated with considerable impairment in quality of life and resilience. Given the lack of approved pharmacological agents for this indication and the frequently recalcitrant disease course, therapeutic options are limited. PATIENTS AND METHODS: Following unsatisfactory therapeutic attempts with other treatment modalities, nine patients (six women; three men) were treated with ustekinumab (45 mg in individuals < 100 kg body weight, 90 mg in individuals > 100 kg) at weeks 0, 4, 12, and 24. Latent tuberculosis was ruled out prior to treatment. Regular follow-up was done at week 4 and 12, and every 12 weeks thereafter. RESULTS: Average age at the beginning of treatment was 48 years. Four patients achieved 75 % improvement in the palmoplantar Psoriasis Area Severity Index (PASI). Overall, there was an average improvement in the palmoplantar PASI of 71.6 % after 24 weeks. Two patients exhibited complete resolution after 24 weeks. Besides local injection site reactions and mild infections, no adverse effects were observed. CONCLUSIONS: This case series provides further evidence for the effectiveness and tolerability of ustekinumab in the treatment of palmoplantar pustular psoriasis. Controlled studies and observations in the context of patient registries are required to assess long-term efficacy and safety as well as the potential therapeutic benefit of intermittent therapy.

Ustekinumab in der Therapie der Pustulosis palmoplantaris - Eine Fallserie mit neun Patienten.

HINTERGRUND: Die Pustulosis palmoplantaris ist eine chronisch entzündliche Hauterkrankung, die mit bedeutenden Einschränkungen der Lebensqualität und der Belastbarkeit einhergeht. Aufgrund von Zulassungsbeschränkungen und einem häufig therapierefraktären Verlauf sind die Behandlungsmöglichkeiten limitiert. PATIENTEN UND METHODIK: Nach zuvor frustranen Therapien erhielten 9 Patienten mit Pustulosis palmoplantaris nach Ausschluss einer latenten Tuberkulose Ustekinumab (45 mg Ustekinumab bei < 100 kg Körpergewicht [KG], 90 mg Ustekinumab > 100 kg KG) in Woche 0, 4, 12 und 24. Reguläre Visiten erfolgten nach 4 und 12 Wochen, im weiteren Verlauf alle 12 Wochen. ERGEBNISSE: Das Durchschnittsalter bei Therapiebeginn betrug 48 Jahre. Drei Patienten waren männlich. Bei n  =  4 Patienten (44,4 %) wurde eine Verbesserung um 75 % des Palmoplantar-Psoriasis-Area-Severity-Index (PPPASI) erreicht. Insgesamt verbesserte sich der PPPASI nach 24 Wochen durchschnittlich um 71,6 %. Eine komplette Abheilung zeigte sich bei n  =  2 Patienten nach 24 Wochen. Bis auf lokale Injektionsreaktionen und leichte Infekte wurden keine unerwünschten Wirkungen beobachtet. SCHLUSSFOLGERUNGEN: Die Fallserie ist ein weiterer Beleg für die Wirksamkeit und Verträglichkeit von Ustekinumab in der Therapie der Pustulosis palmoplantaris. Zur Beurteilung der Langzeitwirkung und -sicherheit sowie der Wirksamkeit einer intermittierenden Therapie sind kontrollierte Studiendaten sowie Beobachtungen im Rahmen von Patientenregistern notwendig.

Prevalence of Obesity in Patients with Psoriasis: Results of the National Study PsoHealth3.

BACKGROUND: Psoriasis is frequently associated with obesity which possibly contributes to reduced treatment response. OBJECTIVES: Assessment of the prevalence of obesity in patients with psoriasis in Germany 2013/2014. PATIENTS AND METHODS: The frequency of overweight and obesity was assessed by the body mass index (BMI) and evaluated according to the severity of psoriasis [Psoriasis Area and Severity Index (PASI)]. RESULTS: This national, cross-sectional survey involved 83 dermatological practices and outpatient clinics, including 1,265 patients (mean age 52 years; 43.4% female). The BMI of patients with psoriasis in 2013/2014 was found to be 28.0 and therefore was significantly higher compared to that of patients with psoriasis in 2007 with a BMI of 26.9 as well as compared to the normal population in 2013 with an overall BMI of 25.9. CONCLUSIONS: The prevalence of obesity in patients with psoriasis is higher than in the normal population. The trend towards a higher BMI in patients with psoriasis continues over time.

Epidemiology and Comorbidity in Children with Psoriasis and Atopic Eczema.

BACKGROUND: First studies have shown that juvenile psoriasis is associated with an increased prevalence of comorbidity. OBJECTIVES: We carried out a data analysis to characterise the profiles of comorbidity in children with psoriasis and atopic eczema. METHODS: Prevalence data were derived from the database of a German statutory health insurance company according to ICD-10 codes L40 (psoriasis) and L20 (atopic eczema) of children up to 18 years insured in 2009. RESULTS: Data sets included 1.64 million persons and 293,181 children. 1,313 children = 0.45% (0.42-0.47) had a diagnosis of psoriasis and 30,354 = 10.35% (10.24-10.47) had a diagnosis of atopic eczema. Obesity, hyperlipidaemia, arterial hypertension and diabetes were more often diagnosed in children with psoriasis in comparison to all children without psoriasis and to those with atopic eczema. CONCLUSION: Children with psoriasis and atopic eczema show different and specific patterns of comorbidity which should be detected early and treated adequately.

Systemic antipsoriatic combination therapy with fumaric acid esters for plaque-type psoriasis: report on 17 cases.

BACKGROUND: In the literature as well as in existing psoriasis guidelines, only little evidence is available on combination regimens with systemic antipsoriatic agents. However, if systemic monotherapy is not efficacious enough to control the disease, a combination therapy might be necessary. OBJECTIVE: To evaluate the use of fumaric acid esters (FAEs) in combination with other antipsoriatic agents in 6 specialized dermatological departments in Germany. METHODS: A systematic retrospective chart review of patients receiving FAEs was performed. RESULTS: A total of 17 cases of patients receiving FAEs combined with at least one other systemic therapy (methotrexate, acitretin, etanercept, cyclosporine, leflunomide and infliximab) to treat psoriasis or psoriatic arthritis were identified. CONCLUSION: FAEs can be combined in an off-label setting with conventional as well as biological agents to treat recalcitrant psoriasis or psoriatic arthritis. Safety monitoring should be taken seriously as no controlled data for these combination regimens exist.

Pimecrolimus 1% cream in the treatment of facial psoriasis: a 16-week open-label study.

BACKGROUND: Facial psoriasis requires a treatment approach other than topical corticosteroids which bear the risk of skin atrophy. Topical pimecrolimus has been shown to be effective in atopic eczema and recently in psoriasis. OBJECTIVE: The aim of this open-label single-center investigator-initiated study was to evaluate the efficacy and safety of pimecrolimus 1% cream in patients with facial psoriasis. METHODS: 20 adults with facial psoriasis were enrolled. Pimecrolimus 1% cream was applied twice daily to psoriatic lesions of the face over an 8-week period. An 8-week follow-up was added. RESULTS: All clinical parameters showed a significant improvement after 8 and 16 weeks compared to baseline. Pimecrolimus 1% cream was effective and well tolerated. CONCLUSIONS: This is the first clinical study with a larger patient cohort reporting a relevant therapeutic effect and favorable safety profile of pimecrolimus 1% cream in facial psoriasis.

Increased levels of lipocalin 2 in palmoplantar pustular psoriasis.

BACKGROUND: Palmoplantar pustular psoriasis (PPP) is a recalcitrant chronic skin disease affecting the palms and soles. OBJECTIVE: To identify and characterize pathogenetic players in PPP. METHODS: Clinical and anamnestic data as well as skin and blood samples of 60 PPP patients were collected. Healthy participants served as controls. Analysis of patient samples and cultured primary skin cells was performed by ELISA, qRT-PCR, and immunohistochemistry. RESULTS: Upon screening of blood mediators in PPP patients, lipocalin 2 (LCN2) emerged as being significantly upregulated compared to healthy participants. LCN2 blood levels were independent of age, sex, or concomitant psoriasis vulgaris. Keratinocytes in PPP skin lesions were important LCN2 producers. In vitro, LCN2 production of these cells was upregulated by IL-1ß and further enhanced by IL-17 and TNF-α, while IL-22 had no effect. Accordingly, a positive relationship between blood IL-1ß and LCN2 levels was evident in PPP. LCN2 blood levels also showed a positive correlation with PPP pustule score, Dermatology Quality of Life Index and blood levels of the pro-atherogenic molecule resistin. CONCLUSIONS: In PPP, increased blood levels of LCN2 indicate an important activity of IL-1ß in the epidermis, may contribute to skin neutrophil infiltration, and may point to an increased pro- atherosclerosis risk.

Hepatitis C and ocular surface disease.

PURPOSE: To assess the frequency of changes in the ocular surface and the presence of hepatitis C virus (HCV) in tear samples of patients with chronic HCV infection. DESIGN: Prospective, nonrandomized, clinical, interdisciplinary, single-center study. METHODS: Seventy-one patients with previously untreated chronic HCV infection and a control group consisting of 66 patients without systemic HCV infection were enrolled in the trial. The patients with HCV infection were screened for ocular symptoms, visual acuity, and ocular changes. Tear production was measured by the Jones test. Conjunctival impression cytologic analysis was performed. The presence of HCV ribonucleic acid (RNA) in tear and blood samples was determined by quantitative polymerase chain reaction. RESULTS: On examination, systemic HCV infection was present for a median of 30 months. Fifty percent of all HCV patients showed a decrease in tear production measured by the Jones test. Apart from epithelial changes related to dry eye syndrome in 12 patients, two patients presented mild peripheral corneal thinning. Polymerase chain reaction analysis detected HCV RNA in five (10%) of 52 tear samples. HCV RNA levels in tear samples (mean, 1.0 x 10(4) copies/ml) were considerably lower than in blood samples (mean, 5.3 x 10(5) copies/ml). CONCLUSIONS: Dry eye syndrome is the most frequently observed ocular feature in HCV infection. Patients with HCV infection (age range, 21 to 60 years) compared with the controls had a significant lower tear production (P = .05). The presence of HCV RNA in 10% of tear samples emphasizes the potential risk of viral transmission through tears.

Efficacy and tolerability of liposomal polyvinylpyrrolidone-iodine hydrogel for the localized treatment of chronic infective, inflammatory, dermatoses: an uncontrolled pilot study.

Infection is common in many chronic, inflammatory skin conditions but is often difficult to treat, in part due to growing bacterial resistance to antibiotics. Liposomal polyvinyl-pyrrolidone (PVP)-iodine hydrogel has a unique mode of action, combining the antiseptic and anti-inflammatory actions of PVP-iodine with the drug delivery and moisturizing properties of liposomes. We investigated the utility of liposomal PVP-iodine to treat infective dermatoses. In this prospective, single-arm (uncontrolled), open-label Phase II pilot study, patients with acne vulgaris (n=30), atopic dermatitis (n=20), impetigo contagiosa (n=10), and rosacea (n=10) received PVP-iodine (3%) hydrogel for ≤4 weeks. Global Clinical Severity score improved for all dermatoses (range: 0.5 for acne vulgaris [p<0.001] to 1.0 for impetigo contagiosa [p=0.011]). Improvements in pain, quality of life, (Freiburg Life Quality Assessment), and Eczema Area and Severity Index scores were also seen. Treatment was well tolerated; most frequent adverse events were burning (14%) or itching (9%) sensations. Thus, liposomal PVP-iodine hydrogel has potential utility as an effective treatment for inflammatory skin conditions associated with bacterial colonization.

Comorbidity as a predictor for drug survival of biologic therapy in patients with psoriasis.

BACKGROUND: Psoriasis often requires lifelong therapy, and adherence to treatment is considered a marker for treatment success. Data on the drug survival of biologics in psoriasis patients with comorbidities are lacking. OBJECTIVES: This study was designed to estimate the long-term drug survival rates of different biologic agents in a cohort of psoriasis patients and to evaluate reasons and predictors for treatment adherence. METHODS: Drug survival rates and outcome parameters in psoriasis patients treated with biologic agents were analyzed. RESULTS: A total of 125 treatment periods with adalimumab (n = 37), efalizumab (n = 9), etanercept (n = 55), infliximab (n = 13), and ustekinumab (n = 11) were administered to 67 psoriasis patients. Patients with psoriatic arthritis (P = 0.010) and without comorbidity (P = 0.033) demonstrated significantly greater rates of drug survival. CONCLUSIONS: The overall efficacy of biologic agents is reduced with time. Patients with the comorbidity of metabolic syndrome demonstrate a loss of adherence to biologic treatment.

Quality of psoriasis care in Germany: results of the national health care study "PsoHealth3".

Two national surveys conducted in 2005 and 2007 indicated deficits in psoriasis care and induced the composition of the ''National Goals for Health Care in Psoriasis 2010-2015''. The aim of this work was to (1) evaluate the quality of care for patients with psoriasis in Germany, (2) compare this with prior psoriasis studies PsoHealth1 (2005) and PsoHealth2 (2007), and (3) review the implementation of national treatment goals. By means of a cross sectional study the following indicators of health care quality were collected: psoriasis severity (Psoriasis Area Severity Index (PASI) and proportion of PASI >20), quality of life (Dermatology Life Quality Index (DLQI) were corporated: proportion of DLQI >10), previous systemic treatment, inpatient treatment, and days absent from work due to psoriasis. Between January 2013 and March 2014, 1265 patients from 82 dermatological centres were included (mean age of 52 years). 9.2 % had a PASI >20 (2007: 11.6 %; 2005: 17.8 %). 21.3 % reported strong quality of life restrictions (DLQI >10) (2007: 28.2 %; 2005: 34.0 %). 59.5 % had received a systemic treatment at least once within the last 5 years (2007: 47.3 %; 2005: 32.9 %). 20.1 % were treated inpatient within the last 5 years (2007: 20.1 %; 2005: 26.9 %). The current data indicate a better health care situation for psoriasis in Germany. The implementation of the S3-Guideline and the ''National Goals for Health Care in Psoriasis 2010-2015'' could have been contributing factors.

Infliximab in the treatment of moderate to severe atopic dermatitis.

BACKGROUND: Chronic use of standard therapies for atopic dermatitis (AD) is associated with variable efficacy and potential side effects. Targeted therapeutic approaches, such as the inhibition of tumor necrosis factor-alpha, may be a novel option. OBJECTIVE: This investigator-initiated, open, prospective, single-center, pilot study was conducted to evaluate the long-term efficacy and safety of infliximab in patients with AD. METHODS: Nine patients with moderate or severe AD were enrolled. AD in these patients was resistant to conventional therapy. Infliximab 5 mg/kg was administered by intravenous infusion at weeks 0, 2, 6, 14, 22, 30, and 38, and patients were followed for 46 weeks. RESULTS: Induction therapy with infliximab significantly improved all clinical parameters, but this improvement was not sustained through maintenance therapy. Only two patients with severe AD achieved an excellent clinical response by 46 weeks. CONCLUSIONS: Infliximab monotherapy may be an additional therapeutic option for the management of refractory severe AD.

Keratolytics and emollients and their role in the therapy of psoriasis: a systematic review.

INTRODUCTION: Psoriasis is a common chronic disease with significant impairment in quality of life. As there is no cure, it often requires lifelong disease control to minimize the development of skin lesions and to relieve symptoms. The aim of this publication is to systematically review the role of currently used emollients and keratolytics in the treatment of psoriasis. METHODS: A systematic literature search was conducted in Medline via PubMed regarding reviews, meta-analyses, and trials published from January 1983 to December 2013 dealing with topical administration of emollients and keratolytics in patients with psoriasis. A subsequent search in EMBASE regarding clinical trials published from 1983 to 2013 was performed to complement the findings. RESULTS: A total of 60 publications met the inclusion criteria for full-text evaluation. While current reviews, meta-analyses, and guidelines state that adjuvant therapy with emollients and keratolytics should be an obligatory part in the therapy of psoriasis to facilitate descaling and/or penetration enhancement, comprehensive trials on these agents are missing, with the exception of combination products containing salicylic acid and corticosteroids. In the mentioned trials, addition of salicylic acid was beneficial in inducing a more rapid onset of action as well as a reduction of severity parameters and the area affected. However, its use has substantial limitations in young children, in patients with renal/hepatic impairment, with widespread psoriasis, those undergoing phototherapy, or those concomitantly treated with calcipotriene/systemic salicylates. CONCLUSION: In view of these shortcomings, there is a need for well-designed studies on suitable keratolytic alternatives to salicylic acid offering an indisputable positive benefit-risk ratio.

Comorbidities, metabolic risk profile and health-related quality of life in German patients with plaque-type psoriasis: a cross-sectional prospective study.

BACKGROUND: Patients with psoriasis experience a higher risk of cardiovascular and metabolic comorbidities and have a high burden of treatment. There is still a gap between treatment options and quality of care. The purpose of this study was to determine the demographic data, comorbidities, and the limitations of quality of life in patients with plaque-type psoriasis. MATERIALS AND METHODS: This epidemiological evaluation was designed as a single-center, cross-sectional, prospective study in Marburg, Germany. To investigate the association between mild to severe psoriasis and comorbidities, data were obtained from 133 patients. RESULTS: The average Psoriasis Area and Severity Index was 13.4, and the average Dermatology Life Quality Index was 6.3. Among the patients with severe psoriasis, 95% had been prescribed systemic treatments. Comorbidities were evaluated, with depression 30.8%, arterial hypertension 39.1%, and hypercholesterolemia 20.3% in all patients. CONCLUSIONS: Our findings underscore the importance of cardiovascular and metabolic risk screening for all patients with psoriasis. There is still a need for systemic treatments and the definition of treatment goals for psoriasis as a systemic inflammatory disease. Such goals should integrate parameters that include comorbidities and an improvement in health-related quality of life.

Tear film osmolarity measurements in dry eye disease using electrical impedance technology.

PURPOSE: Tear film hyperosmolarity is recognized as an important pathogenetic factor in dry eye syndrome, but difficulties in its measurement have limited its utility in the recent past. This prospective, nonrandomized, clinical single-center study investigates the osmolarity in tear samples of patients with keratoconjunctivitis sicca compared with healthy controls. METHODS: One hundred thirty-three patients [aged 58 years (51-64 years), 86 women and 47 men] with moderate to severe keratoconjunctivitis sicca and 95 controls [aged 52 years (48-61 years), 55 women and 40 men] were enrolled in the trial. Tear samples were collected directly from the inferior lateral tear meniscus. Inclusion criteria were a tear breakup time of less than 5 seconds, a Schirmer test with anesthesia less than 5 mm, and positive symptoms (Ocular Surface Disease Index score > 83). Tear film osmolarity was analyzed by the TearLab osmometer. RESULTS: In our study, patients with moderate to severe keratoconjunctivitis sicca showed a tear film osmolarity of 320 mOsmol/L (301-324 mOsmol/L). The results of the control group were 301 mOsmol/L (298-304 mOsmol/L). Our results revealed a significantly higher tear film osmolarity in patients with moderate to severe keratoconjunctivitis sicca compared with the control group. The sensitivity was 87%, and the specificity was 81%. CONCLUSIONS: Our results approved the referent value in moderate to severe dry eye of approximately 316 mOsmol/L, as described in the literature. The results showed a significantly higher tear film osmolarity in patients with severe keratoconjunctivitis sicca compared with the healthy controls. Testing tear film osmolarity can be a very effective objective diagnostic tool in the diagnosis of dry eye disease.