Impact of off-label use regulations on patient care in dermatology - a prospective study of cost-coverage applications filed by tertiary dermatology clinics throughout Germany.

BACKGROUND: In dermatology, a medical speciality with a relatively high number of rare diseases, physicians often have to resort to off-label treatment options. To avoid claims, physicians in Germany can file a cost-coverage request (off-label application, OL-A). OBJECTIVES: Our aim was to investigate the extent to which the current regulations affect patient care. MATERIAL AND METHODS: Prospective cohort study among tertiary dermatology clinics throughout Germany, consecutively including OL-As (05/2019-09/2020) and assessing the follow-up correspondence. We modelled regressions to assess factors associated with cost-coverage decisions and the time needed by health insurers to process the OL-As. RESULTS: Thirteen clinics provided data on 121 OL-As, two of which applied for on-label treatments. Of the remaining 119 OL-As, 70 (58.8%) were immediately approved and 44 (37.0%) rejected. Including cases with one or more appeals, 87 of 119 OL-As (73.1%) were finally approved and 26 (21.9%) rejected. There was an association of the final approval rate with (1) the class of medication/treatment, with approval rates being significantly lower for JAK inhibitors than for biologics (OR 0.16, 95%-CI: 0.03-0.82); (2) German state, with approval rates being lower in eastern than in western states (OR 0.30, 95%-CI 0.12-0.76); and (3) cost of the intervention (no linear trend). However, none of these predictors was significant in our multiple logistic regression models. The median health insurer's processing time (first response) was 29 days (IQR 22-38). Our analyses showed no evidence of an association with the predictors we assessed. In cases approved, the median time from the decision to file an OL-A to the actual initiation of the treatment was 65.5 days (IQR 51-92). CONCLUSIONS: Our study points to substantial delays and inequalities in the provision of timely health care for dermatological patients with rare diseases, often involving treatments for which there is no adequate approved therapy.

[Current dermatology guidelines in Germany and Europe : A selection of clinically relevant recommendations]. / Aktuelle dermatologische Leitlinien in Deutschland und Europa : Eine praxisorientierte Übersicht ausgewählter Empfehlungen.

Clinical practice guidelines are systematically developed decision aids for specific medical conditions. In Germany, national dermatology guidelines are developed chiefly under the aegis of the German Dermatological Society in collaboration with the Professional Association of German Dermatologists. European and international dermatological guidelines also exist and are developed by a range of organisations, such as the European Centre for Guidelines Development, which was founded by the European Dermatology Forum in 2018. In the years 2019 and 2020, new or updated German national guidelines were published on topics such as pathological scars (hypertrophic scars and keloids), cutaneous lupus erythematosus, pyoderma grangrenosum, anal pruritus, anal eczema, anal canal and anal rim carcinomas, as well as the prevention of HPV-associated neoplasms through vaccination, syphilis and the systemic treatment of neurodermitis. A new European guideline on lichen planus closes a gap in the spectrum of guidelines available in Germany. Key recommendations and relevant changes in the guidelines are presented in this article.

2019 IUSTI-Europe guideline for the management of anogenital warts.

This guideline is an update of the 2011 European Guideline for the Management of Anogenital Warts. It is intended to support best practice in the care of patients with anogenital warts by including evidence-based recommendations on diagnosis, treatment, follow-up and advice to patients. It is intended for use by healthcare professionals in sexual healthcare or dermato-venereology clinics in Europe but may be adapted for use in other settings where the management of anogenital warts is undertaken. As a European guideline, recommendations should be adapted according to national circumstances and healthcare systems. Despite the availability of vaccine to prevent HPV types 6 and 11, the cause of >95% anogenital warts, they remain an important and frequent health problem. The previous systematic review of randomized controlled trials for anogenital warts was updated. The changes in the present guideline include the following: Updated background information on the prevalence, natural history and transmission of human papillomavirus (HPV) infection and anogenital warts. Key recommendations for diagnosis and treatment have been graded according to the strength of the recommendation and the quality of supporting evidence. 5-fluorouracil, local interferon and photodynamic therapy have been evaluated and included as potential second-line treatment options. Evidence of the impact of HPV vaccination on the incidence of anogenital warts has been updated.

Prioritizing topics in guideline development: results of a two-phase online survey of dermatologist members of the EADV.

BACKGROUND: Most clinical guidelines in dermatology are encyclopaedic, covering a disease and its aetiology, diagnosis, treatment and prevention in their entirety. The usability and uptake of guideline recommendations might be improved by guidelines that are more concise and address specific questions ranked by users according to their perceived importance. OBJECTIVE: To survey the largest association of dermatologists in Europe, identify which questions in their everyday practice they felt would benefit from short, evidence-based guidance and rank these systematically. METHODS: A two-phase online survey using a structured ranking approach and the members directory of the European Academy of Dermatology and Venereology (EADV). RESULTS: The first survey yielded 265 suggestions, indicating a response rate of 3.7%. We grouped all responses according to themes and subsequently combined these into a list of 35 broader topics. These were presented to all members of the EADV in the second survey (response rate: 9.7%), which yielded a list of the top 10 topics participants felt were most in need of guidance. The first three were 'Systemic drug treatment in dermatology during pregnancy and for women wishing to have children in the near future', 'alopecia areata' and 'interpretation of laboratory results in connective tissue diseases'. CONCLUSION: Our two-phase survey of EADV members and a structured ranking process were practical to implement and yielded a list of the top 10 topics in dermatology and venereology for guideline development. Guideline dissemination needs to be improved, and practical, more concise guidelines may facilitate efforts to do so.

The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria.

This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

[Diagnostics and management of herpes zoster ophthalmicus]. / Diagnostik und Management des Herpes zoster ophthalmicus.

Herpes zoster (HZ, shingles) represents the secondary manifestation of an infection with varicellazoster virus (VZV). A reactivation of dormant VZV in the ophthalmic branch of the fifth cranial nerve leads to ophthalmic HZ (HZO). The predominantly older and immune compromised patients often present with eye involvement (approximately 50%) as well as characteristic skin changes. Clinical manifestations include the cornea and conjunctiva but anterior uveitis and (rarely) acute retinal necrosis may also occur. Associated sensory symptoms that range from paresthesia to severe pain may severely affect the quality of life. Particularly in immunocompromised and/or elderly patients, HZO is associated with complicated courses. Systemic antiviral treatment and an adequate pain medication are the mainstay of the recommended management. The present article provides an overview of the contents of the current consensus-based European guidelines on the management of HZ with a specific focus on HZO.

Topical treatments for scalp psoriasis: summary of a Cochrane Systematic Review.

People with chronic plaque psoriasis often have lesions on the scalp that are difficult to treat. This report is a summary of a Cochrane review on the efficacy and safety of topical treatments for scalp psoriasis. For quality-of-evidence assessment, we used the Grading of Recommendations Assessment, Development and Evaluation Working Group approach. Only randomized controlled trials (RCTs) were eligible for inclusion. We searched the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS; ongoing trials; indexes of included studies and screened abstracts of six psoriasis-specific conferences up to August 2015. We included 59 RCTs, with 11 561 participants overall. Most findings were limited to short-term treatments (< 6 months). According to the clinician and patients' self-assessment, a corticosteroid-vitamin D combination (e.g. betamethasone dipropionate plus calcipotriol) and corticosteroids of high and very high potency were better than vitamin D. The two-compound combination was superior to the corticosteroid alone, but the additional benefit was small. Reporting of quality-of-life data was insufficient. The two-compound combination and corticosteroids caused fewer withdrawals due to adverse events than vitamin D. There was no difference between the two-compound combination and corticosteroid monotherapy concerning this outcome. Overall the evidence was of moderate quality. Evaluation of other topical treatments was limited. Given the comparable safety profile and only slim benefit of the two-compound combination over the corticosteroid alone, monotherapy with generic topical corticosteroids of high and very high potency may be fully acceptable for short-term therapy. More quality-of-life data and long-term assessments are needed.

European consensus-based (S2k) Guideline on the Management of Herpes Zoster - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 2: Treatment.

Herpes zoster (HZ, shingles) is a frequent medical condition which may severely impact the quality of life of affected patients. Different therapeutic approaches to treat acute HZ are available. The aim of this European project was the elaboration of a consensus-based guideline on the management of patients who present with HZ, considering different patient populations and different localizations. This interdisciplinary guideline aims at an improvement of the outcomes of the acute HZ management concerning disease duration, acute pain and quality of life of the affected patients and at a reduction in the incidence of postherpetic neuralgia (PHN) and other complications. The guideline development followed a structured and pre-defined process, considering the quality criteria for guidelines development as suggested by the AGREE II instrument. The steering group was responsible for the planning and the organization of the guideline development process (Division of Evidence-Based Medicine, dEBM). The expert panel was nominated by virtue of clinical expertise and/or scientific experience and included experts from the fields of dermatology, virology/infectiology, ophthalmology, otolaryngology, neurology and anaesthesiology. Recommendations for clinical practice were formally consented during the consensus conference, explicitly considering different relevant aspects. The guideline was approved by the commissioning societies after an extensive internal and external review process. In this second part of the guideline, therapeutic interventions have been evaluated. The expert panel formally consented recommendations for the treatment of patients with HZ (antiviral medication, pain management, local therapy), considering various clinical situations. Users of the guideline must carefully check whether the recommendations are appropriate for the context of intended application. In the setting of an international guideline, it is generally important to consider different national approaches and legal circumstances with regard to the regulatory approval, availability and reimbursement of diagnostic and therapeutic interventions.

European consensus-based (S2k) Guideline on the Management of Herpes Zoster - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 1: Diagnosis.

Herpes zoster (HZ, shingles) is a frequent medical condition which may severely impact the quality of life of affected patients. Different therapeutic approaches to treat acute HZ are available. The aim of this European project was the elaboration of a consensus-based guideline on the management of patients who present with HZ, considering different patient populations and different localizations. This interdisciplinary guideline aims at an improvement of the outcomes of the acute HZ management concerning disease duration, acute pain and quality of life of the affected patients and at a reduction of the incidence of postherpetic neuralgia and other complications. The guideline development followed a structured and predefined process, considering the quality criteria for guidelines development as suggested by the AGREE II instrument. The steering group was responsible for the planning and the organization of the guideline development process (Division of Evidence based Medicine, dEBM). The expert panel was nominated by virtue of clinical expertise and/or scientific experience and included experts from the fields of dermatology, virology/infectiology, ophthalmology, otolaryngology, neurology and anaesthesiology. Recommendations for clinical practice were formally consented during the consensus conference, explicitly considering different relevant aspects. The guideline was approved by the commissioning societies after an extensive internal and external review process. In this first part of the guideline, diagnostic means have been evaluated. The expert panel formally consented recommendations for the management of patients with (suspected) HZ, referring to the assessment of HZ patients, considering various specific clinical situations. Users of the guideline must carefully check whether the recommendations are appropriate for the context of intended application. In the setting of an international guideline, it is generally important to consider different national approaches and legal circumstances with regard to the regulatory approval, availability and reimbursement of diagnostic and therapeutic interventions.

[Current guidelines in dermatology : A selection of clinically relevant recommendations]. / Aktuelle dermatologische Leitlinien : Eine praxisorientierte Übersicht ausgewählter Empfehlungen.

Guidelines are systematically developed decision aids for specific medical conditions. The German Dermatological Society, together with the German Professional Association of Dermatologists, takes the lead in the development of the guidelines for dermatology in Germany. In addition to national guidelines, European and international guidelines also exist. In 2014 and 2015 German guidelines on the following topics were newly developed or updated: cutaneous larva migrans, anticoagulation during dermatosurgery, pemphigus vulgaris and bullous pemphigoids, Mohs surgery, anal dysplasia, and anal carcinoma in HIV-infected patients. European guidelines on psoriasis vulgaris and hand eczema were updated among others. An international guideline on actinic keratosis was also published. The guidelines are available at www.awmf.org and www.euroderm.org .