HPE Grunenthal handbook - Page 4

(CKD) type 3 and above, advanced heart failure, high blood pressure, and use of loop diuretics and thiazide diuretics. Diabetes mellitus and metabolic syndrome also contribute to the increased reabsorption of uric acid via hyperinsulinism. Who is affected by gout? Gout mainly affects men aged 40 or over. Earlier onset can be observed, from adolescence and before the age of 30, and has a definite genetic origin (mainly the ABCG2 gene). Gout is uncommon in women before menopause, because oestrogens have a uricosuric effect, that is, they increase the urinary elimination of uric acid. What are the consequences of gout attacks? Gout attacks usually begin abruptly in the foot, especially at the joint at the base of the big toe. Attacks usually trigger at night after a high-fat meal or after certain beverages. The pain is intense (in the order of 7–8 on a numerical pain scale of 10) and becomes maximal in less than 24 hours. Locally, joint swelling sets in, with often intense, local redness. Joint function is markedly impaired. The pain will gradually improve and disappear within 15 days, and medications can reduce the duration or stop the attack. In early disease, the joint returns to normal between attacks. Arthritis will repeat itself at an unpredictable rate, with the time between each attack gradually becoming shorter. Other joints can be affected: first, the foot and ankle, then the knee or, much later, the upper limb. Gout should be the diagnosis in cases of recurrent acute arthritis in men. What are the other manifestations? Apart from gout attacks, deposits of agglomerated microcrystals (tophi) can form in a number of sites including: Achilles’ tendons, patellar tendons, or even ear cartilage (helix). These clinically visible deposits reflect the importance of crystal stocks in the body. They can also be detected through imaging (joint ultrasound, dual energy scanner or dual energy CT). 4 Treating the crisis The mechanism of the gout attack is complex but the key inflammatory molecule is interleukin-1 (IL-1). There are three standard anti-inflammatory treatments (standard of care): colchicine; non- steroidal anti-inflammatory drugs (NSAIDs); and oral/ injectable corticosteroids. 5,6 In any case, the patient should be advised to start treatment as soon as possible after the first recognisable signs of the gout attack. Therefore, it is recommended patients carry colchicine or NSAIDs with them, ‘in their pocket or on their bedside table’. 1 Colchicine has good efficacy, particularly in Table 1 Conditions and comorbidities associated with gout • Ageing • Diabetes mellitus • Metabolic syndrome • Hypertension • Coronary heart disease, myocardial infarction • Cerebral vascular accident • Peripheral obliterans arteritis • Chronic kidney disease • Atrial fibrillation 4 | 2018 | hospitalpharmacyeurope.com The mechanism of the gout attack is complex, but the main inflammatory molecule involved in interleukin-1 regards to microcrystalline inflammation, when it is started early at low doses: 1–1.5mg might be sufficient on the first day. Conventional NSAIDs (naproxen, indomethacin) or COXIBs (etoricoxib) are effective if prescribed in full doses for a short period of time (3–5 days). They are at risk of adverse reactions and comorbidities dictate their use or otherwise. They are contraindicated in cases of renal failure and anti- vitamin K medication. Naproxen has the advantage of improved cardiovascular safety. Oral corticosteroids (prednisone 30mg/day, for 3–4 days) are also effective. They are useful in the event of adverse reactions, ineffectiveness or contraindication to colchicine or NSAIDs. Poorly controlled diabetes mellitus, heart failure or hypertension might limit their use. Canakinumab, an anti-IL-1 monoclonal antibody, has European marketing authorisation and is effective in the treatment of difficult-to-treat gout attacks (classified as patients who have had at least three gout attacks over a year, who are poorly relieved by NSAIDs and colchicine, and who are intolerant to both drugs and cannot be treated repeatedly with prednisone). However, the long duration of action of canakinumab (three months), along within increased risk of infections and its cost limit its use. Anakinra, an IL-1 receptor antagonist, is sometimes used off-label; its half-life is short but the risk of infection exists with prolonged administration. What are the comorbidities associated with gout? The main difficulty in the management of gout is related to the associated comorbidities (Table 1). They give rise to contraindications or dose limitations of so-called ‘standard of care’ drugs and hypouricaemic drugs. Diabetes mellitus and its macro- and microvascular complications, cardiovascular diseases and chronic renal failure (CKD) are the main comorbidities (see dedicated articles in this handbook). Some of these comorbidities such as diabetes and metabolic syndrome and CKD are also involved in the development of hyperuricaemia. Comorbidities are already known to the patient’s treating physician and pharmacist: in other words, the occurrence of acute arthritis of the foot in such a patient must be consistent with the diagnosis of recent gout. What is the real treatment for gout? The cause of the disease is the accumulation of urate microcrystals due to chronic hyperuricaemia; and so the real treatment comprises reducing uricaemia with urate-lowering therapies (ULT) below the threshold of urate solubility. The threshold is 360µmol/l (6.0mg/dl) for uncomplicated gout and 300µmol/l (5.0mg/dl) for severe gout with tophi. Two classes of ULT are available: xanthine oxidase inhibitors (XOIs), which block uric acid synthesis; and uricosurics, which block the mechanism of increased reabsorption of uric acid into the renal tubule. XOIs There are two XOIs: allopurinol and febuxostat. Allopurinol is available at doses of 100, 200 and 300mg (this is the reference treatment in various treatment guidelines). It is inexpensive and effective, except in certain circumstances where its effectiveness may be reduced, such as in CKD, in particular. The initial dose is 100mg/day, or even 50mg/