POS0508 A RANDOMISED CONTROLLED TRIAL COMPARING ANAKINRA VERSUS STEROIDS FOR THE TREATMENT OF GOUT ATTACKS IN PEOPLE WITH RENAL DISEASE (ASGARD): A FEASIBILITY STUDY

Background

Title: A study to determine the feasibility of undertaking a definitive randomised multi-centre, double-blind, double-dummy controlled study of Anakinra vs. intramuscular methylprednisolone acetate for acute gout attacks in patients with chronic kidney disease. Gout is common in people with chronic kidney disease (CKD) where effective treatments like non-steroidal anti-inflammatory drugs are contra-indicated. Anakinra, an IL-1 receptor antagonist, could be an important treatment option for treating gout flares in people with CKD (eGFR<60mls/min/1.73m2).

Objectives

Aim: to assess the feasibility of the design and procedures for a future definitive randomised trial of anakinra in people with moderate to severe CKD. Specific objectives were to: test recruitment and retention; test eligibility criteria; collect outcome data to inform sample and power calculations for a future trial; collect economic data to inform a future economic evaluation; and assess capacity for to scale up to a larger trial.

Methods

Design: two-parallel group, double-blind, double-dummy, multicentre randomised feasibility trial comparing subcutaneous anakinra 100mg for 5 days with a single injection of intramuscular methylprednisolone acetate 120 mg for treating gout flares in people with CKD (eGFR <60mls/min/1.73m2). Participants were planned to be recruited from five sites in the South East region of the UK over 15 months, the target sample size was 32. Proposed primary outcome was self-assessed pain intensity using Visual Analogue Scale (VAS) (0–100mm) and 5-point Likert scale. Proposed secondary outcome measures consisted of physician assessment of joint; assessment of activity limitation and quality of life using Health Assessment Questionnaire Disability Index, 36-Item Short Form Survey, Five-level EuroQol Five-Dimensional Questionnaire and Lower Extremity Functional Scale.

Results

21 patients were randomised (anakinra 10, depo-Medrone 11), 3 were lost to follow-up. Mean age was 72 years and mean eGFR was 43.6 mls/min/1.73m2. The first metatarsophalangeal joint was the commonest joint affected (10/21). 2 participants were taking urate-lowering therapy although 16 reported previous flares. Mean overall change in pain from baseline was 35.88 by VAS and 1.69 by Likert scale. Functional assessment and quality of life assessment was highly completed. The baseline assessment was low for the SF-36 and HAQ-DI, the LEFS showed a trend of improvement and the HAD-QI showed a decline from day 7 to week 8. Health resource use was higher when assessed by health records compared to self-reporting. Qualitative feedback from participants alluded to high questionnaire burden and delays in receiving treatment. There were no serious adverse events or reactions. One patient needed rescue medication 10 days later for recrudescence of flare in the anakinra arm. We met three out of its four success criteria: recruiting at least 70% of eligible patients; 85% of participants completing 5 out of 7 pain outcome measure; and ≤10% treatment cross-over or failure.

Conclusion

Our study did not meet its entire feasibility target due to poor recruitment. This was compounded by various factors which may be possible to overcome. Aspects to rationalise the study would be utilising VAS and patient reported Likert, without physician assessment of joints. Functional assessment and quality of life assessment could be reconciled to using EQ-5D-5L and SF-36 at day 1, day 7 and week 8 minimising the questionnaire burden. We did not find good functional assessment with the LEFS and HAQ-DI, the gout flare score may be a possible alternative, bearing in mind the impact of questionnaire burden. A future definitive trial may be feasible if we are able to overcome challenges in recruitment, better ways of case finding, and initiating randomised treatment during gout flare. Our study is the first gout study looking specifically at people with advanced CKD and showed good safety and efficacy with these agents for this group of patients.

REFERENCES:

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Acknowledgements:

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Disclosure of Interests

None Declared.