Gout (Hyperuricemia): Drug Therapy

Goiter (goiter) change therapy goals

  • In an acute attack of gout, the primary goal is to relieve the patient’s discomfort (analgesia) and anti-inflammation (anti-inflammation).
  • In cases of confirmed gout disease, causal uric acid-lowering therapy should be started as soon as possible: The goal is to permanently reduce hyperuricemia and thus prevent a new gout attack and further complications as far as possible.
    • The goal of uric acid-lowering therapy is to permanently lower serum uric acid below the target value of <6 mg/dl (<360 μmol/l). The target value is defined by the physicochemically defined solubility of uric acid.
    • In severe tophous gout, a target value of < 5 mg/dl (300 μmol/l) should be aimed for.
  • The aim of therapy is furthermore the favorable influence of associated comorbidities (e.g. renal insufficiency/kidney weakness).

Therapy recommendations

  • Acute gout attack (initiation of therapy within 12-24 h after onset of pain; duration of therapy: usually.

    <14 d until symptoms resolve):

    Supportive cooling compresses and immobilization of the affected joint may be prescribed. Untreated, a gout attack lasts a few hours to several days. It passes again on its own, with or without treatment. Since 2012, according to a published guideline of the American College of Rheumatology, uric acid-lowering therapy can certainly be started during an acute gout attack (see also under). For attack prophylaxis can be recommended thereby Colchicum in low dosage of 0.5-1 mg/day for about 3-6 months.

  • Uric acid-lowering therapy: in cases of confirmed gout disease, causal, uric acid-lowering therapy should be started as soon as possible – even during an acute attack (under anti-inflammatory/anti-inflammatory therapy).
    • Indications according to guidelines:
      • recurrent gout attacks
        • 1-2 gout attacks/year
      • Chronic gouty arthritis (manifestation of gout at joints).
      • Gouty tophi (gouty nodules; if necessary, detection by imaging).
      • Kidney or urinary stone history
      • Renal insufficiency (kidney weakness)
        • ≥ stage 2 (glomerular filtration rate 60-89 ml/min/1.73 m2) if there is a history of gouty attacks and hyperuricemia is present

      In long-term therapy, a uric acid serum level < 6.0 mg/dl (≈ 357 μmol/l) should be aimed for; in severe gout (frequent gouty attacks and evidence of tophi) also < 5 mg/dl until all tophi have disappeared.At the beginning of therapy, checks of serum uric acid every 4 weeks are useful; later quarterlyNote: A uric acid-lowering therapy already started should not be interrupted because of a gouty attack occurring under it 10].

    • Drug therapy
      • Uricostatic agents (first-line therapy): allopurinol (1st-line therapy) or febuxostat (2nd-line therapy; lowers serum uric acid significantly more than allopurinol); if necessary. also combination of allopurinol with lesinurad (URAT1 inhibitor)Note: Contraindication (contraindications) in coronary heart disease (CHD), decomp. heart failure; notes on increased overall mortality (total mortality rate) and increased mortality with concomitant NSAID administration (non steroidal anti inflammatory drugs).
      • Uricosurics (drugs that increase renal (“via the kidneys”) uric acid excretion) (second choice).
      • If necessary, urinary alkalinization (transfer of the pH of urine from the acidic to a more alkaline range) with potassium sodium hydrogen citrate or basic minerals such as calcium, potassium and magnesium citrate.
      • Duration of therapy: uric acid lowering therapy is a continuous therapy:
        • Patients without tophi: at least 5 years
        • Patients with tophi: until resolution of all tophi and then another 5 years (to empty uric acid stores); aim for lower target than in non-tophyseal gout (e.g., ≤ 5 mg/dl)
    • Seizure prophylaxis: If gout is confirmed, uric acid-lowering therapy under antiinflammatory protection-with colchicine at low doses (1 to 2 times 0.5 mg daily) for 3 to 6 months/if colchicine is contraindicated with NSAIDs or glucocorticoids-should be initiated. This can be done immediately. Contrary to common practice, a controlled study shows that initiation of allopurinol therapy in acute relapse is feasible.
  • See also under “Further therapy”.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Non-steroidal anti-inflammatory drugs are drugs that have anti-inflammatory and analgesic effects. They include indomethacin and ibuprofen. They are the standard medications for acute gout attacks in Germany.Indications: Treatment of pain and, to a lesser extent, swelling.

Colchicine

Colchicine inhibits phagocytosis (uptake of foreign substances by phagocytes) of urate. It is the oldest drug in the treatment of acute gout attack. However, it is rarely used in Germany because of the increased risk of overdose. AkdÄ Drug Safety Mail | 67-2018: Due to the narrow therapeutic range of the active ingredient colchicine, overdoses with partly fatal outcome are possible. Therefore, the dosage recommendations have been changed: A daily dose of 2 mg on the first day, two to three times 0.5 mg on the second and third days, and two times 0.5 mg on the fourth day, if necessary, is considered sufficient (maximum dose per gout attack: 6 mg).

Glucocorticoids

Oral glucocorticoids, such as prednisone, have an antiphlogistic (anti-inflammatory) effect and are therefore used in addition to the above medications for acute gout attack. According to one study, the incidence of gastrointestinal side effects such as nausea, vomiting, and dyspepsia was lower with glucocorticosteroid therapy than with NSAIDs.

Uricosteroids

Uricosteroids, such as allopurinol or febuxostat, inhibit the synthesis of uric acid inhibition of the enzyme xanthine oxidase. The dose of allopurinol should be increased slowly-beginning with 100 milligrams per day-until the serum uric acid level is about half of what the respective laboratory indicates as the norm. The dose should be increased by 100 milligrams every two to four weeks. Febuxostat therapy should be started at 80 mg/d. If the uric acid level does not fall < 6 mg/dl in the next two to four weeks, the dose should be increased to 120 mg/d. Allopurinol therapy

  • Reduces the risk of nonfatal myocardial infarction/heart attack.
  • Of patients with uric acid levels above 6 mg/dl resulted in an 11% lower rate of the combined end point (nonfatal myocardial infarctions and strokes) and a 32% lower all-cause mortality (all-cause death rate) in treated subjects compared with nontreated controls.
  • May not halt further loss of renal function in patients with chronic renal failure.

Side effects of allopurinol: gastrointestinal (nausea, diarrhea), skin reactions (1 in 1. 196 patients developed a severe skin reaction; Stevens-Johnson syndrome or toxic epidermal necrolysis; most common after about 1 month; risk was low after patients had tolerated the drug for 3 months; high allopurinol dose (more than 100 mg/day; RR 2.78; 1.75-4.43) also increased risk (2.78; 1.75-4.43)), allergic reactions, reactive gout attackCaution: patients of Asian origin, eg. e.g., Han Chinese, Korean, and Thai, frequent association of HLA subtype HLA-B* 5801 with the occurrence of Stevens-Johnson syndrome.There is an increased risk of skin reactions in chronic renal insufficiency.A population-based cohort study suggests no association between therapy with at least 300 mg allopurinol and severe renal disease; doses of ≥ 300 mg allopurinol decreased the risk of decline in renal function by 13%. Warnings for Febuxostat:Do not use febuxostat in patients with ischemic heart disease or decompensated heart failureFDA: number of cardiac deaths and total deaths were increased in the febuxostat group

Uricosurics

Uricosurics increase uric acid excretion, for example, benzbromarone.Indication: when uricostatic agents cannot be used or are not sufficiently effective

Monoclonal antibodies

In patients with insufficient efficacy or contraindication to this agent and recurrent gout attacks (≥ 3 per year), the guideline recommends subcutaneous administration of canakinumab (monoclonal human IL-1β antibody) [recommendation grade B].

Supplements (dietary supplements; vital substances)

Appropriate dietary supplements should contain the following vital substances:

Legend* Risk group* * Urine alkalinization (transfer of the pH of urine from the acidic to a more alkaline range) with potassium sodium hydrogen citrate or basic minerals such as calcium, potassium and magnesium citrate. Note: The listed vital substances are not a substitute for drug therapy. Dietary supplements are intended to supplement the general diet in a given life situation.