HPE Grunenthal handbook - Page 12

be safely used for a prolonged period of time: intensified urate-lowering therapy with XOI plus uricosuric, that is, rapidly debulking ULT. Lifelong XOI monotherapy might be adequate to keep the patient out of the danger zone for gout attacks after an intensified XOI + uricosuric time period. Case study 4 A 62-year-old man having renal transplantation 30 years prior, myocardial infarction 25 years prior; calciphylaxis cutis one year prior with Staphylococcal bacteraemia from leg ulcers due to calciphylaxis and portal hypertension with hypersplenism without liver cirrhosis. During his hospital stay, he developed a fulminant left-sided arthritis of PIP5 left sided and MTP1 bilaterally. He remembered having a similar attack annually over the last four years only during hospital stays Physical examination A man recovering from a pneumosepsis with oligoarthritis and redness over affected joints with weight 74kg and BMI 20 with redness over MTP1 on both sides and PIP 5 on the left side. Ultrasonography Double contour sign a the MTP1 cartilage bilaterally and many intraarticular reflections in his left-sided PIP 5. Puncture of MTP1 Tophous debris at polarisation microscopy X-rays forefeet Not done. Gout calculator 13 (highly suggestive for gout) Laboratory test Serum urate 710 micromolar (12.10mg/dl) with serum creatinine 227 and CRP 200; haemoglobin 6.2mM and platelets 116; fractional urate excretion was not measured as total renal function was clearly a major problem. Course Dietary advice and started allopurinol 50mg daily aiming for a redefined target: any lowering of serum urate plus trying to get a setting without ongoing attacks In the most severe cases, renal function is diminished to a very low level (<20ml/min) with still significant tophaceous disease or bulky disease. The primary goal is then redefined as getting the patient free of attacks with a glucocorticoid and/or colchicine regimen, or, if not tolerated, interleukin-1 blockade such as with canakinumab or off-label anakinra. Simulateneously, any urate-lowering strategy with dietary restrictions regarding purines and ULT with allopurinol or febuxostat can be 12 | 2018 | hospitalpharmacyeurope.com References 1 Roddy E, Doherty M. Epidemiology of gout. Arthritis Res Ther 2010;12:223. 2 Zhu Y, Pandya BJ, Choi HK. Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007–2008. Am J Med 2012;125:679–87. 3 Richette P et al. Revisiting comorbidities in gout: a cluster analysis. Ann Rheum Dis 2015;74:142–7. 4 Jansen TL, Janssen M. The American College of Physicians and the 2017 guideline for the management of acute and recurrent gout: treat to avoiding symptoms versus treat to target. Clin Rheumatol 2017;36:2399–402. 5 Richette P et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2017;76(1):29–42. 6 Jansen TL. Rational pharmacotherapy (RPT) in goutology: define the serum uric acid target & treat-to-target patient cohort and review on urate lowering therapy (ULT) applying synthetic drugs. Joint Bone Spine 2015;82(4):225–9. undertaken. If renal function still exceeds the 20ml/ min level, adding a uricosuric should be considered. In some instances, a uricolytic uricase therapy can be offered, particularly if a bridging debulking therapy of XOI + uricosuric is considered ineffective. A three-month debulking period of uricase can be quite effective if conservative XOI and/or uricosuric can be continued afterwards. Without alternative long-term options, short-term uricase is of no use unless monthly uricase can be offered for chronic maintenance therapy. The predominant problem with PEGylated uricase for long-term use is antibody formation, resulting in loss of efficacy or anaphylaxis, and the slightly increased mortality associated with these potent serum urate reductions. Case study 5 A healthy 38-year-old female without a family history of gout and suffering from a similar attack in MTP1 two years prior reported an MTP1 arthritis in the ninth week of her second pregnancy. Healthy lifestyle but no specific diet. She had polycystic ovary syndrome, hypertension, and obesity. Physical examination A healthy young female with weight 100kg and BMI 30.8 with redness over the right MTP1 Ultrasonography Double contour sign rightsided MTP1 with grade 2-3 power Doppler; X-rays forefeet: not possible because of pregnancy. Gout calculator score 11 (highly suggestive for gout). Laboratory test Serum urate 550 micromolar (9.25mg/dl) with GFR >60 serum creatinine 90; urate excretion 4.3mM (72.28mg/dl) ; fractional urate excretion 4.3% Course To ascertain the gout diagnosis, a puncture was carried out and many monosodium urate needles were present in the aspirate; initially dietary advice (reduce purine ingestion and increase coffee intake) with low dose prednisone 10mg daily for 3–5 days if needed. This resulted in a significant improvement during her pregnancy, but afterwards, serum urate was unchanged and allopurinol treatment was started. Conclusions The patient journey in gout clearly shows that patients might be looking for medical attention for chronic arthropathy or severe acute attacks on one hand, or for a structural solution of the hyperuricaemia-induced sequelae on the other. Patients often only present to specialised care at an advanced stage, and then only a few treatment options remain; the earlier GPs are involved in the patient journey, the more options for individualised pharmacotherapeutic regimens exist. 5 Clinicians might be helped by realising the patient journey and the different phenotypes of gout patients: with high purine/calorie intakes and normal versus subnormal urate excretion. In finding personalised effective treatment, one should start with dietary advice and the possibility of lifelong treatment assessed; 5 some patient phenotypes are clearly more into lifelong treatment than others. If urate excretion is low but effective, predefined targets cannot be reached easily and if renal excretion still is adequate, then uricosurics in addition with uptitrated XOIs may be considered as any serum urate target is often within reach. 5,6 The more pharmaceutical options available, the more phenotyping is warranted to optimise an individual’s journey. However, once safe and very potent urate-lowering regimens are available, these might become the new panacea for any gout patient.