IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis: rationale and study protocol of a phase 3b, randomised, double-blind, multicentre study in participants with moderate-to-severe plaque-type psoriasis (GUIDE).

BACKGROUND: Guselkumab is an interleukin (IL)-23 pathway blocker with proven efficacy in patients with moderate-to-severe plaque psoriasis. Early intervention with guselkumab may result in changes to the clinical disease course versus later intervention. METHODS AND ANALYSIS: Here we present the rationale and design of a phase 3b, randomised, double-blind, multicentre study (GUIDE), comparing treatment effects of guselkumab in patients with short (≤2 years) or longer (>2 years) duration of plaque-type psoriasis, measured from first appearance of psoriatic plaques. Participants achieving skin clearance (Psoriasis Area and Severity Index (PASI)=0) by week 20 and maintaining complete clearance at week 28 visit ('super-responders' (SRe)) will be randomised to continue approved maintenance dosing every 8 weeks (q8w) versus an investigational maintenance dosing interval of 16 weeks (q16w) until week 68. Primary endpoint: proportion of participants in the q8w vs q16w arms with absolute PASI <3 at week 68. Participants with PASI <3 at week 68 will be withdrawn from guselkumab treatment for up to 48 weeks. Participants not achieving SRe criteria (non-SRe) will remain in the study with q8w guselkumab dosing through week 68. Additional to serum samples obtained from all patients, skin biopsies and whole-blood samples will be taken from SRe and non-SRe participants at various time points in optional substudies. Analyses include: genetics; immunophenotyping (fluorescence-activated cell sorting); gene and protein expression profiling; immunohistology. By merging clinical endpoints with mechanistic findings, this study aims to elucidate how IL-23 blockade with guselkumab can modify the disease course by altering molecular and cellular drivers that cause relapse after treatment withdrawal, particularly among SRe. ETHICS AND DISSEMINATION: Approval obtained from ethics committee Medical Council Hamburg, Germany (PVN5925). GUIDE is compliant with the Declaration of Helsinki. TRIAL REGISTRATION NUMBER: Registered at ClinicalTrials.gov (NCT03818035). All primary endpoint results (prespecified analyses) will be submitted to peer-reviewed, international journals within 18 months after primary completion date.

Similar efficacy, safety, and immunogenicity of the biosimilar BI 695501 and adalimumab reference product in patients with moderate-to-severe chronic plaque psoriasis: results from the randomized Phase III VOLTAIRE-PSO study.

Background: BI 695501 is an approved biosimilar to Humira® reference product (RP). Research design and methods: In this randomized Phase III trial (VOLTAIRE-PSO), patients with moderate-to-severe chronic plaque psoriasis received BI 695501 or adalimumab RP (24-week treatment). Primary efficacy endpoint: the proportion of patients with ≥75% reduction in Psoriasis Area and Severity Index (PASI 75) response at week 16 (±18% equivalence limits for two-sided 95% confidence interval between treatment groups). Safety, pharmacokinetics, and immunogenicity were also assessed. Results: Baseline characteristics were balanced between treated groups (BI 695501, n = 159; adalimumab RP, n = 158). PASI 75 response rates (full analysis set, n = 158; n = 157) were 68.2% (BI 695501) and 70.4% (adalimumab RP) at week 16 (95% CI: -14.4%, 8.7%), and 75.3% and 72.4%, at week 24, respectively. At week 24, 41.5% (BI 695501) and 44.9% (adalimumab RP) of treated patients had treatment-emergent adverse events (AEs), 3.1% and 4.4% had serious AEs, and 0.0% and 1.9% had AEs of special interest. Of treated patients, 75.3% (BI 695501) and 77.9% (adalimumab RP) were anti-drug antibody-positive. Conclusion: These data demonstrate equivalent efficacy and highly similar safety and immunogenicity between BI 695501 and adalimumab RP in patients with chronic plaque psoriasis. Study identifier: NCT02850965.

Efficacy and safety of fumaric acid esters in combination with phototherapy in patients with moderate-to-severe plaque psoriasis (FAST).

BACKGROUND: While treatment of patients with moderate-to-severe psoriasis using a combination of fumaric acid esters (FAE, Fumaderm® ) and phototherapy (UV) is common practice, there have been hardly any studies investigating this regimen. Available information is limited to data from a small pilot study. The objective of the present study was to evaluate FAE/UV combination therapy in a larger patient cohort with moderate-to-severe psoriasis. PATIENTS AND METHODS: In this prospective noninterventional multicenter study, data from patients treated with FAE/UV combination therapy was assessed with regard to efficacy (PGA' PASI, DLQI, EQ-5D), safety, and dosage over a twelve-month period. The findings were subsequently compared to data from a previous retrospective study on FAE monotherapy. RESULTS: Data from 363 patients was included in the analysis. Efficacy measures improved substantially on combination therapy. Compared to FAE monotherapy, FAE/UV therapy led to a faster clinical response, however, there was no difference in efficacy after 12 months. Neither the duration nor the type of phototherapy had an impact on efficacy. In general, combination therapy was well tolerated. Seven percent of patients experienced adverse events. CONCLUSIONS: FAE/UV combination therapy is effective and well tolerated in patients with moderate-to-severe psoriasis. Such treatment may induce a faster therapeutic response, and appears to be useful, particularly in the first three months of FAE therapy.

Wirksamkeit und Sicherheit von Fumarsäureestern in Kombination mit Phototherapie bei Patienten mit moderater bis schwerer Plaque-Psoriasis (FAST).

HINTERGRUND: Die Behandlung von Psoriasis-Patienten mit einer Kombination aus Fumarsäureestern (FSE, Fumaderm® ) und Phototherapie (UV) ist verbreitet, wurde aber im Rahmen von Studien wenig untersucht. Bisher liegen lediglich Daten aus einer kleinen Pilotstudie vor. Intention dieser Studie war, eine FSE/UV-Kombinationsbehandlung an einem größeren Patientenkollektiv mit mittelschwerer bis schwerer Psoriasis zu untersuchen. PATIENTEN UND METHODIK: In dieser prospektiven, multizentrischen, nichtinterventionellen Studie wurden Daten von Patienten mit FSE/UV-Kombinationstherapie hinsichtlich der Wirksamkeit (PGA' PASI, DLQI, EQ-5D), Sicherheit und Dosierung über einen Zeitraum von zwölf Monaten erfasst und mit Daten einer retrospektiven Studie mit FSE-Monotherapie verglichen. ERGEBNISSE: Es wurden Daten von 363 Patienten ausgewertet. Unter der Kombinationstherapie verbesserten sich alle Wirksamkeitsparameter deutlich. Im Vergleich zur Monotherapie mit FSE konnte durch die Kombination mit UV ein schnellerer Wirkeintritt erzielt werden, wobei nach zwölf Monaten kein Unterschied in der Wirksamkeit bestand. Die Dauer und Art der Phototherapie zeigte keinen Einfluss auf die Wirksamkeitsparameter. Allgemein wurde die Kombinationstherapie gut vertragen. Unerwünschte Ereignisse wurden bei 7 % der Patienten berichtet. SCHLUSSFOLGERUNGEN: Die FSE/UV Kombinationstherapie zeigt eine gute Wirksamkeit und Verträglichkeit und kann zu einem schnelleren Wirkeintritt führen. Eine Kombinationstherapie erscheint vor allem in den ersten drei Monaten der FSE Behandlung sinnvoll.

Efficacy and safety of fumaric acid esters in patients with psoriasis on medication for comorbid conditions - a retrospective evaluation (FACTS).

BACKGROUND: Safety and efficacy of fumaric acid esters (FAE) in patients with psoriasis requiring treated comorbidit condition were investigated. PATIENTS AND METHODS: Data collected from 7 dermatology centers were used for a retrospective analysis of patients treated continuously with FAE for at least 6 weeks who required at least one medication for a comorbid condition. The records were analyzed at baseline and after 1, 3, 6, 12 and 24 months of therapy. Safety parameters were monitored and the severity of skin symptoms was assessed by 'Physician's Global Assessment' (PGA). RESULTS: A total of 69 patients with moderate to severe psoriasis and a mean duration of 27.4 months of continuous treatment were included in the study. In less than 5% were interactions between FAE and co-medications observed. Changes of hepatic, renal or hematological laboratory parameters were usually insignificant and required a modification of FAE treatment in less than 12% of the cases. The percentage of patients documented as markedly improved or clear was 61% after 6 months, 77% after 12 months, and 75% after 24 months of therapy. CONCLUSIONS: In patients with moderate to severe psoriasis on co-medications, FAE were effective and safe without any noteworthy drug interactions.

Lichen planus and hepatitis virus infections: causal association?

BACKGROUND: The causal association between hepatitis virus infections and lichen planus (LP) remains a matter of controversy. Reliable figures for German patients are still lacking. PATIENTS AND METHODS: We analyzed the prevalence of serum antibodies against hepatitis B and C viruses (HBV, HCV) in 265 LP patients and compared the results to 257 patients with chronic urticaria (URT) and 222 patients with malignant melanoma (MM). Additionally, we analyzed age- and sex-specific differences. RESULTS: The prevalence of HBV (13.2 % or 14.7 %) antibodies was significantly higher in patients with LP and URT patients than in the MM control group (HBV: 5.4 %, p < 0.001). The prevalence of HCV antibodies among LP and URT patients (2.6 % or 0.8 %) was not significantly greater (p > 0.05) than in MM patients (0.4 %). The prevalences of HBV and HCV in the MM control group were comparable to those in the general German population (HBV: 5-8 %, HCV: 0.4-0.7 %). An analysis by sub-groups showed that these differences resulted from sex- and age-dependent prevalences. HBV antibodies were significantly more common only in male LP patients (16.1 %) and in male (20.0 %) and female URT patients (15.6 %) aged 31-60 years. The greater prevalence of HCV in female LP patients older than 60 years of age was not significant. CONCLUSIONS: LP is not specifically associated with hepatitis B or C antibodies in the Caucasian population of Germany. The higher prevalences of HBV antibodies found in LP and URT patients may be a reflection of age- and sex-related factors rather than disease-specific exposure to HBV infections. The increased prevalences seen in patients with LP or URT compared to MM patients may suggest that HBV infection serves as an unspecific trigger for a specific immune reaction of another origin.

Evidence-based (S3) guideline for the treatment of psoriasis vulgaris - Update: "Therapeutic options" and "Efalizumab".

In February 2009, the European Medicines Agency's (EMEA) Committee for Medicinal Products for Human Use (CHMP) had recommended the suspension of efalizumab's (Raptiva) marketing authorization, because its benefits in the treatment of psoriasis were modest, while there was a risk of serious side effects in patients receiving the medicine, including the occurrence of progressive multifocal leukoencephalopathy (PML). The guideline group has changed the guideline accordingly.

Acupuncture in acute herpes zoster pain therapy (ACUZoster) - design and protocol of a randomised controlled trial.

BACKGROUND: Acute herpes zoster is a prevalent condition. One of its major symptoms is pain, which can highly influence patient's quality of life. Pain therapy is limited. Acupuncture is supposed to soften neuropathic pain conditions and might therefore act as a therapeutic alternative. Objective of the present study is to investigate whether a 4 week semi-standardised acupuncture is non-inferior to sham laser acupuncture and the anticonvulsive drug gabapentine in the treatment of pain associated with herpes zoster. METHODS/DESIGN: Three-armed, randomised, placebo-controlled trial with a total follow-up time of 6 months. Up to estimated 336 patients (interim analyses) with acute herpes zoster pain (VAS > 30 mm) will be randomised to one of three groups (a) semi-standardised acupuncture (168 patients); (b) gabapentine with individualised dosage between 900-3600 mg/d (84 patients); (c) sham laser acupuncture. Intervention takes place over 4 weeks, all patients will receive analgesic therapy (non-opioid analgesics: metamizol or paracetamol and opioids: tramadol or morphine). Therapy phase includes 4 weeks in which group (a) and (c) consist of 12 sessions per patient, (b) visits depend on patients needs. Main outcome measure is to assess the alteration of pain intensity before and 1 week after treatment sessions (visual analogue scale VAS 0-100 mm). Secondary outcome measure are: alteration of pain intensity and frequency of pain attacks; alteration of different aspects of pain evaluated by standardised pain questionnaires (NPI, PDI, SES); effects on quality of life (SF 36); analgesic demand; alteration of sensoric perception by systematic quantitative sensory testing (QST); incidence of postherpetic neuralgia; side effects and cost effectiveness. Credibility of treatments will be assessed. DISCUSSION: This study is the first large-scale randomised placebo controlled trial to evaluate the efficacy of acupuncture compared to gabapentine and sham treatment and will provide valuable new information about the clinical and physiological effects of acupuncture and gabapentine in the treatment of acute herpes zoster pain. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if acupuncture can be shown to be an effective treatment strategy in acute herpes zoster pain. TRIAL REGISTRATION: NCT00885586.

"Borrelia-associated early-onset morphea": a particular type of scleroderma in childhood and adolescence with high titer antinuclear antibodies? Results of a cohort analysis and presentation of three cases.

BACKGROUND: Morphea is an inflammatory autoimmune skin sclerosis of unknown etiology. A causative role of Borrelia burgdorferi infection has been controversially discussed, but no conclusive solution has yet been achieved. OBJECTIVE: Intrigued by 3 young patients with severe Borrelia-associated morphea and high-titer antinuclear antibodies, we retrospectively examined the relationship between Borrelia exposure, serologic autoimmune phenomena and age at disease onset in morphea patients. METHODS: In 90 morphea patients the presence of Borrelia-specific serum antibodies was correlated to the age at disease onset and the presence and titers of antinuclear antibodies. Patients with active Borrelia infection or high-titer antinuclear antibodies due to systemic sclerosis or lupus erythematosus served as controls. RESULTS: We observed a statistically highly significant association between morphea, serologic evidence of Borrelia infection, and high-titer antinuclear antibodies when disease onset was in childhood or adolescence. LIMITATIONS: Because pathogenic Borrelia species may vary in different geographic regions the relevance of Borrelia infection in morphea induction may show regional variations. CONCLUSION: B burgdorferi infection may be relevant for the induction of a distinct autoimmune type of scleroderma; it may be called "Borrelia-associated early onset morphea" and is characterized by the combination of disease onset at younger age, infection with B burgdorferi, and evident autoimmune phenomena as reflected by high-titer antinuclear antibodies. As exemplified by the case reports, it may take a particularly severe course and require treatment of both infection and skin inflammation.

Photodynamic therapy for granuloma annulare: more than a shot in the dark.

BACKGROUND: Granuloma annulare (GA) is a benign granulomatous and inflammatory skin disorder. The pathogenesis remains enigmatic and convincingly effective treatment options are not available. Inspired by a report showing photodynamic therapy (PDT) to be effective in a single patient with GA, we sought to evaluate this benefit in a series of patients with GA. OBSERVATIONS: PDT was performed in 7 consecutive patients with histologically confirmed GA located at the extremities. First, 20% ALA gel was applied under an occlusive dressing for 5 h, followed by illumination with 100 J/cm(2) by a standard red-light source. In total, 2-3 PDT sessions were performed, with an interval of 2-4 weeks between each session. Treatment was stopped when complete remission was achieved or when GA lesions remained unchanged after 2 consecutive PDT sessions. The overall response rate was 57%. In 2 patients (29%), GA cleared completely, in 2 patients (29%) the skin lesions improved markedly and in 3 patients (43%) no clinical response could be observed. CONCLUSION: These promising results should be evaluated in larger controlled studies. In selected patients, PDT might be a valuable recruit for the sparse armory available to treat GA.

Disseminated eruptive giant mollusca contagiosa in an adult psoriasis patient during efalizumab therapy.

Molluscum contagiosum is a common viral skin infection in children with atopic diathesis and not rare in HIV patients. We report a 45-year-old psoriasis patient who developed eruptive mollusca contagiosa during an antipsoriatic treatment with efalizumab.

[Implementation of the S3-guidelines for systemic and UV therapy of moderate to severe psoriasis vulgaris by an algorithm]. / Implementierung der S3-Leitlinien zur systemischen und UV-Therapie der mittelschweren bis schweren Psoriasis vulgaris durch einen Therapiealgorithmus.

The recently published German S3- guidelines for the treatment of psoriasis vulgaris offer an extensive evidence-based documentation and evaluation of currently available treatment modalities. In order to incorporate this detailed information into the actual treatment decisions in individual patients, we have transformed the recommendations regarding phototherapy and systemic therapies into an algorithm. This algorithm should allow a stepwise treatment approach in adult patients with moderate to severe psoriasis, in whom topical therapy is not sufficient. It can also facilitate documentation of treatment. In our hands the treatment algorithm proved to be feasible and reliable in a large number of patients.

Sequential use of infliximab and etanercept in generalized pustular psoriasis.

Generalized pustular psoriasis is a dramatic potentially life-threatening psoriasis variant and represents a major therapeutic challenge. Tumor necrosis factor alpha (TNF-alpha) inhibitors have been shown to be highly effective in psoriasis vulgaris and psoriasis arthritis. Currently, TNF-alpha can be targeted therapeutically by 2 different approaches. TNF-alpha antibodies show a fast onset of action and a long-lasting activity. Soluble TNF-alpha receptors have a slower onset and a shorter duration of activity, which allows a rapid cessation of the drug's activity in the case of adverse events. Here we report that a remission of generalized pustular psoriasis achieved by the TNF-alpha antibody infliximab was maintained by long-term application of the soluble TNF-alpha receptor etanercept. Sequential therapy with TNF-alpha antibodies and TNF-alpha receptors may represent a novel concept that combines a rapid onset of action in the initiation therapy with a lower risk for severe adverse events in the maintenance treatment of pustular psoriasis.

Detection of the 47-kilodalton membrane immunogen gene of Treponema pallidum in various tissue sources of patients with syphilis.

Polymerase chain reaction (PCR) was used to detect the 47-kDa immunogen gene of Treponema pallidum in peripheral blood mononuclear cells (PBMCs), skin lesions, and serum, but less consistently in purified granulocytes or ejaculates of patients with manifest and latent syphilis. Therefore, skin lesions and PBMCs may serve as the most reliable sources for a PCR-based diagnosis of syphilis.

[Diagnostic pitfall: herpes simplex recidivans on the finger]. / Diagnostischer Fallstrick: Herpes simplex recidivans am Finger.

Herpes simplex recidivans is one of the most common dermatological infections. In typical (perioral, labial or genital) localization, the diagnosis is simple and often made by the patient. In atypical locations, the disease may be misdiagnosed by the physician. A 28-year-old patient presented with recurrent herpes simplex virus exacerbations on his left index finger, accompanied by neuralgic pains and lymphadenitis. He had been misdiagnosed by a variety of specialists for several years and had often been unable to work. The diagnosis of recurrent herpes simplex was made by the patient's history and the clinical symptoms and was confirmed by the detection of Herpes simplex virus-specific DNA by PCR.