Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson’s disease

An increase in the efficiency of clinical trial conduct has been successfully demonstrated in the oncology field, by the use of multi-arm, multi-stage trials allowing the evaluation of multiple therapeutic candidates simultaneously, and seamless recruitment to phase 3 for those candidates passing an interim signal of efficacy. Replicating this complex innovative trial design in diseases such as Parkinson’s disease is appealing, but in addition to the challenges associated with any trial assessing a single potentially disease modifying intervention in Parkinson’s disease, a multi-arm platform trial must also specifically consider the heterogeneous nature of the disease, alongside the desire to potentially test multiple treatments with different mechanisms of action. In a multi-arm trial, there is a need to appropriately stratify treatment arms to ensure each are comparable with a shared placebo/standard of care arm; however, in Parkinson’s disease there may be a preference to enrich an arm with a subgroup of patients that may be most likely to respond to a specific treatment approach. The solution to this conundrum lies in having clearly defined criteria for inclusion in each treatment arm as well as an analysis plan that takes account of predefined subgroups of interest, alongside evaluating the impact of each treatment on the broader population of Parkinson’s disease patients. Beyond this, there must be robust processes of treatment selection, and consensus derived measures to confirm target engagement and interim assessments of efficacy, as well as consideration of the infrastructure needed to support recruitment, and the long-term funding and sustainability of the platform. This has to incorporate the diverse priorities of clinicians, triallists, regulatory authorities and above all the views of people with Parkinson’s disease

Doença de Mucha-Habermann (variante febril úlcero-necrótica) com acometimento mucoso exuberante: relato de caso Febrile ulceronecrotic Mucha-Habermann disease with exuberant mucosal involvement: case report

A pitiríase liquenoide é dermatose incomum, idiopática, com espectro clínico-histopatológico onde inclui a forma varioliforme aguda (doença de Mucha-Habermann), sua variante febril úlceronecrótica e a forma crônica. Manifestações sistêmicas podem ocorrer na variante febril úlcero-necrótica, com relatos de casos fatais em adultos. Relata-se o caso de um paciente jovem, com diagnóstico clínico e histopatológico de doença de Mucha-Habermann, variante febril úlcero-necrótica, e acometimento mucoso exuberante, fato ocasional, mesmo nas formas mais graves de pitiríase liquenoide. Além do aspecto clínico inusitado, demonstra-se excelente resultado terapêutico, com a associação de prednisona e metotrexato.<br>Pityriasis lichenoides is a rare idiopathic cutaneous disorder, with a clinical-histopathological spectrum comprising the acute varioliform form (Mucha-Habermann's disease), its febrile ulceronecrotic variant, and its chronic form. Systemic manifestations may occur in the febrile ulceronecrotic variant, with reports of adult mortality. The case of a young male patient with clinical and histopathological diagnosis of Mucha-Habermann&#8217;s disease, febrile ulceronecrotic variant, with severe mucosal involvement - an occasional incidence even in the most severe forms of pityriasis lichenoides - is presented. In addition to the atypical clinical aspect, an excellent therapeutic result is shown with the association of prednisone and methotrexate