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THU0505 The Development of A New European Regulatory Guideline on The Clinical Investigation of Medicinal Products for The Treatment of Gout
  1. E. Rook,
  2. on behalf of Rheumatology/Immunology Working Party, European Medicine Agency
  1. Medicine Evaluation Board, Utrecht, Netherlands

Abstract

Background The EMA's Committee for Medicinal Products for Human Use (CHMP) prepares scientific guidelines in consultation with regulatory authorities in the EU Member States, to help applicants prepare marketing-authorisation applications for human medicines, including in the domain of rheumatology. These guidelines are developed by the Rheumatology/Immunology Working Party (RIWP), which is composed of European experts selected from or associated with national agencies.

Objectives There is a need of new and safe treatment options for the prevention and treatment of gout attacks, and several are under development. Moreover, the EULAR an ACR have updated their recommendations for the diagnosis and treatment of gout. Imaging techniques become increasingly important in diagnosing and monitoring of gout. Therefore, a CHMP guidance is developed to promote drug development and European consensus on the choice of the endpoints and design of the studies.

Results The development plan and endpoints will mainly be related to the mode of action of the drug. This may either urate lowering therapy (ULT), or anti-inflammatory drugs. For ULT products, serum uric acid (SUA) could serve as a surrogate endpoint. The primary endpoint is defined as SUA levels below a target level of 6 mg/dl, for a period of 3 consecutive months. For tophaceous gout patients SUA levels <5 mg/dl are considered a more appropriate primary endpoint. Tophi can be included as secondary endpoint. At present, imaging of tophi by e.g. ultrasound is considered as supportive evidence, since it's validation has been limited thus far to case series of selected patients. The treatment goal of anti-inflammatory drugs could be the acute treatment of flares. The primary endpoint should reflect a clinically relevant reduction in pain, in a relatively short time frame of 12–24 hrs. A specific goal of anti-inflammatory drugs could be the prophylaxis of flares upon initiation of ULT. The primary endpoint should be the mean number of flares within 3–6 months after the start of ULT. In general, parallel, randomised, double-blind, active-controlled trials should be performed for both ULT and anti-inflammatory drugs.

In addition, long-term anti-inflammatory treatment options may be developed for refractory gout patients with chronic gouty arthropathy, without symptom-free intervals. A suitable primary endpoint could be the reduction of pain, with the improvement of function (e.g. measured by HAQ-DI or Patient's Global Assessment) as co-primary endpoint.

The development of treatment options for asymptomatic hyperuricaemia is beyond the scope of this guideline.

Conclusions A European regulatory guideline for the development of new treatment options of gout is under development. The guideline is open for public consultation.

  1. European Medicine Agency's Concept paper on the need of the guideline on clinical investigation of medicinal products for the treatment of gout, EMA/CHMP/937321/2011, 14 May 2012

Disclosure of Interest None declared

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