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PhD Defence Carly Janssen

gout: patients, medicine and society

Carly Janssen is a PhD student in the department of Psychology, Health & Technology. Her supervisor is prof.dr. M.A.F.J. van de Laar from the Faculty of Behavioural, Management and Social sciences (BMS).

Gout is a common form of inflammatory arthritis belonging to the family of rheumatic conditions. It is caused by deposited uric acid crystals in the synovial fluid of joints following prolonged hyperuricemia. The (sudden) onset of such an inflammatory reaction is referred to as an acute gout flare, which is characterized by symptoms as joint pain, swelling and tenderness of the affected joint. Repeated attacks of acute gout flares may lead to worsening of the disease and development of tophi (lumps of crystals), also commonly referred to as chronic gout. In general, gout may lead to patients experiencing impaired physical functioning and decreased quality of life.

In this thesis, various studies are presented related to gout and hyperuricemia, divided among three parts. The first part contains studies that focus on the clinical management of gout and hyperuricemia. The main study of this section, a multicenter, double-blind randomized controlled trial, revealed that the interleukin-1 inhibitor anakinra is an efficacious, alternative treatment option for managing acute gout flares by showing non-inferiority to conventional treatments in reducing pain in patients with an acute gout flare. In addition, anakinra showed to reduce other gout-related symptoms (e.g. joint swelling, tenderness) in a similar manner as conventional therapy. As such, these findings further support the validity of the role of interleukin-1 in gout. Furthermore, studies in this section showed that the long-term management of gout and hyperuricemia is suboptimal in terms of the one-year medication compliance and persistence of urate-lowering therapy (ULT) in the Netherlands, and the high frequency of gout flare recurrences within three months after starting this therapy in gout patients. At last, this section revealed that the concept of treating to a serum urate target with ULT needs further substantiation in gout, but may be beneficial in lowering serum urate levels.

The studies described in the second part of this thesis focused on measuring the effects of gout on patients from the patient perspective using patient-reported outcome measure (PROMs). It was shown that more evidence on the measurement properties of commonly used PROMs in gout clinical research should become available, based on modern psychometric techniques and methodological sound studies. That is, the systematic review in this section showed that for many of the commonly used PROMs in gout, limited evidence is available regarding their validity and reliability. At present, only the physical functioning subscale of the Short Form-36 version 2 had sufficient evidence supporting its measurement properties that were included in this review. In addition, this study showed that a variety of PROMs are used to measure a single outcome. To enhance comparability among studies in gout using PROMs, it may become necessary to standardize outcomes. In that respect, in this section the Gout Attack Intensity Score (GAIS) was introduced as a score for use in acute gout trials for determining the severity of gout flare symptom intensity, considering the levels of patient-reported pain, swelling and tenderness. The GAIS was shown to be a reliable and responsive PROM. 

At last, the third part of this thesis examined the societal burden of gout and hyperuricemia in terms of the cost-effectiveness of the treatment options for these diseases. Results of this study showed that the ULT allopurinol and febuxostat were both cost-effective compared to no ULT. At higher willingness-to-pay thresholds (>€25,173) febuxostat had a greater probability of being cost-effective compared to allopurinol, while below this threshold allopurinol was the favored treatment. For the management of acute gout flares, the conventional therapies offered similar health economic implications, although naproxen was overall most favored. Compared to conventional therapies, anakinra was not cost-effective, driven by its higher costs per treatment, even though it did yield the highest utility. As such, from a health economic perspective, anakinra would most likely be suited as a second-line therapy for the management of acute gout flares.