Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review

Abstract

Paediatric Rheumatology International Trials Organisation (PRINTO) and the Eurofever/Eurotraps Projects. AbstractObjective To evaluate the response to treatment of autoinflammatory diseases from an international registry and an up-to-date literature review.Methods The response to treatment was studied in a web-based registry in which clinical information on anonymised patients with autoinflammatory diseases was collected retrospectively as part of the Eurofever initiative. Participating hospitals included paediatric rheumatology centres of the Paediatric Rheumatology International Trial Organisation network and adult centres with a specific interest in autoinflammatory diseases. The following diseases were included: familial Mediterranean fever (FMF), cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor (TNF)-receptor associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), pyogenic arthritis pustulosis acne (PAPA) syndrome, deficiency of interleukin-1 receptor antagonist (DIRA), NLRP12-related periodic fever and periodic fever aphthosis pharyngitis adenitis (PFAPA) syndrome. Cases were independently validated by experts for each disease. A literature search regarding treatment of the abovementioned diseases was also performed using Medline and Embase.Results 22 months from the beginning of the enrolment, complete information on 496 validated patients was available. Data from the registry in combination with evidence from the literature confirmed that colchicine is the treatment of choice for FMF and IL-1 blockade for DIRA and CAPS. Corticosteroids on demand probably represent a valid therapeutic strategy for PFAPA, but also for MKD and TRAPS. Patients with poorly controlled MKD, TRAPS, PAPA or FMF may benefit from IL-1 blockade; anti-TNF treatment may represent a possible valuable alternative. ConclusionsIn the absence of high-grade evidence, these results could serve as a basis for therapeutic guidelines and to identify candidate drugs for future therapeutic trials.

Recommendations for the management of autoinflammatory diseases

“…In CAPS, there is no evidence for the efficacy of disease-modifying antirheumatic drugs or biological therapy other than IL-1 blockade 50. Some patients benefit from non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, mostly as on-demand symptom relief next to IL-1 blocking agents 39 50.…”

Trapped without a diagnosis: Tumour necrosis factor receptor-associated periodic syndrome (TRAPS)

“…Anakinra provides complete resolution of symptoms and inflammatory response in over 80% of patients with TRAPS and is therefore the first-line adjunctive treatment in patients requiring long-term corticosteroids 7. In a population of children, when anakinra was withdrawn after 15 days of treatment, the disease relapsed within an average of 5 days but resolved with reintroduction of anakinra.…”

In silico validation of the Autoinflammatory Disease Damage Index

“…Furthermore, the majority of studies on new biological therapies for AIDs are recently initiated, with limited follow-up, hence the potency of these drugs to prevent or stop the development of damage is not yet known 3 7 8. The Autoinflammatory Disease Damage Index (ADDI) has been developed to enable assessment of the long-term burden of AIDs in a standardised manner, as a comprehensive tool measuring damage in patients with AIDs 5. Although developed for the four main monogenic AIDs, the ADDI may potentially also be useful in other diseases with autoinflammatory features 9 10…”