Gout is very common disease and here is the presentation with latest drugs and guidelines for management of gout.

2. ● “King of diseases” & “Disease of kings”
● Encompasses heterogenous group of diseases
● Normal value of uric acid is 5-6 mg/dl
● Solubility exceeds if monosodium urate level > 6.8 mg/dl
● Prevalence ranges from 2.6% - 47.2%
Heterogenous group of diseases includes-
- hyperuricemia, arthritis due to monosodium urate monohydrate crystals, tophi deposits
in joint leading to deformity, renal disease, uric acid nephrolithiasis

3. ● Term is derived from Latin word gutta meaning “drop”
● First identified by the Egyptians in 2640 BC
● Galen was the first to describe tophi
● “Gout” was 1st used by Dominican monk Randolphus
● Later “gout” was described by Thomas Sydenham, the
famous English physician who himself was a patient of gout

5. ● Acute arthritis
● Night attacks
● First attack usually at 40-60 yrs (M:F is 3:1)
● Three stages of gout
- Asymptomatic hyperuricemia
- Acute and Intercritical gout
- Chronic gouty arthritis

6. - Acute arthritis is the most common early clinical manifestation of gout.
-Attacks usually occurs at night with dramatic joint pain an swelling. Most attacks
especially early in the course of disease are monoarticular with predisposition to 1st
MTP (Podagra)
- The intervals between attacks of gouty arthritis are referred to as intercritical
periods. A patient who has intercritical gout simply has gout that has caused attack(s)
of inflammation in a joint(s) in the past, but it is not visibly active at the time the doctor
is evaluating the patient.

8. ● Terminate acute attack
● Prevent recurrence
● Prevent or reverse complications of disease
● Prevent or reverse deleterious conditions associated with
gout.
- Prevent recurrence of acute gouty arthritis
- Deleterious conditions are- Obesity, Hypertriglyceridemia and Hypertension.
- Complications of the disease resulting from the deposition of sodium urate or uric acid crystals
in joints, kidneys or other sites

9. ● Moderate calorie intake
● Proportionally increased protein and unsaturated fat
● Foods to be avoided -:
1. Meat - pork, beef, lamb, liver
2. Fish - salmon, cod, mackerel
3. Vegetables- green peas, cauliflower, spinach, mushroom
4. Avoid alcohol (especially beer)
● Drink plenty of water and fruits
● Use olive or sunflower oil for cooking

10. -Among alcohol “beer” is responsible for gout- Choi et al in Lancet. 2004 Apr 17.
- Olive oil and sunflower oil have Polyphenol which have anti-inflammatory property.
They also inhibit xanthine oxidase. (Journal of Funtional Food)

11. ● “ Is treatment really necessary ? ”
● Ask a few questions to yourself
● Following data are pertinent-
- Study by Nakagawa published in Am J Nephrol (2002;23:2)
- Renal disease mostly related to poorly controlled
hypertension
- Hyperuricemia as independent risk factor for CAD ????
Questions are- What is the cause? , Are associated findings present, Has any damage to tissue or
organs occurred as a result of hyperuricemia.

12. ● Better to refrain from treatment
● Rare exceptions-
- hereditary cause of uric acid production
- at risk of acute uric acid nephropathy
● Better to find and treat the cause
● Address the associated factors
Associated factors like hyperlipidemia - Fenofibrate
hypertension – Losartan
These have modest uricosuric effects.

13. ● NSAIDs
● Colchicine
● Corticosteroid preparation
● Adrenocorticotrophic hormone (ACTH)
● IL-1ꞵ inhibitors
● Icepacks
Timing of initiation of therapy is more important than the choice of drug
Colchicine preferred when diagnosis of gout is in doubt and NSAID is preferred when diagnosis is
confirmed.

14. ● Mechanism of Action
● Traditional dosing
● 2012 ACR guideline recommendation-
- 1.2 mg stat followed by 0.6 mg 1 hr later and then 0.6 mg
every 12 hrs till attack has subsided.
● Low therapeutic index (Css – 0.5-3 ng/ml)
● Stop medication at first sign of GI irritation.
● Care should be taken if prescribed with Macrolides,
Cyclosporine, Statins

15. MOA- Blocks the processing of IL-1ꞵ, inhibit E-selectin mediated adhesiveness,
decreases IL1 expression, Leucotriene-B4 expression, and Phospholipase A2 production.
- Traditional dosing was 0.5-0.6 mg taken hourly unit one of the three occurred- joint
pain relieved, GI symptoms, 10 doses taken.
- Css is steady state plasma concentration achieved after acute treatment.
- Toxic effects also occur at approx. 3 ng/ml , so the adverse effects almost coincide
with the relief in joint symptoms.
- Macrolides and cyclosporine are inhibitors of CYP3A4 and P-glycoprotein which are
required for the elimination of colchicine. So, colchicine in plasma increases to toxic
level. Statins cause myopathy so concomitant use will increase the chance of
myopathy.

16. ● Indomethacin “Traditional choice”
- 50 – 75 mg stat followed by 50 mg every 6-8 hr with max.
200mg in 1st 24 hrs
- To prevent relapse cont. this dose for next 24 hrs followed
by tapering to 50 mg 6-8 hr for next 2 days.
● Naproxen 500 mg twice daily
● Ibuprofen 800 mg thrice daily
● Celecoxib 800 mg stat followed by 400 mg after 12 hrs then
400 mg twice daily.

17. ● Reserved if intolerance to NSAID or Colchicine
● If monoarticular ----------- Intra-articular route preferred
● High dosage (0.5 mg/kg) required if given per oral
● Flare ups have been note after withdrawal
High dose is required because flare ups have been seen at 7.5 mg to 15 mg per day dose. (Study
by Clive et al in J Am Soc Nephrol)

18. ● Best in the field
● Single injection im (25-80 IU)
● Mechanism-
- Stimulates adrenal gland
- interferes with inflammatory process
● Too expensive
● Not approved by FDA (2010)
- At this doe of 25-80 the acute attack of gout is terminated.
- Stimulating adrenal gland will produce corticosteroid, inflammatory process is interfered by
activating melanocortin receptor-3
- Because of it’s expense this drug has not been handy for most of the patients

19. ● Anakinra
- 100 mg sc daily for 3 days
● Rilonacept
- Schumacher et al. 2012 (160 mg/week)
- Many phase II and III trials going on
● Canakinumab
- cost and adverse effect
- Approved by European Commission
- Single sc injection 150 mg

20. - Anakinra and Rilonacept block both IL-1α and IL-1ꞵ but Canakinumab is specific for
IL-1ꞵ.
- In study by Schumacher results were that, during the 16-week trial, 39/42 patients
receiving placebo had flares versus 9/41 patients receiving rilonacept.
- Canakinumab is a fully human monoclonal anti-IL-1β antibody with a 28-day half-life.
Approved by FDA and EMEA for Cryopyrin-Associated Autoinflammatory Syndromes
(CAPS).
- Canakinumab is approved by ONLY European Commission and NOT by FDA.

22. Evidence level A- Supported by multiple trials
Evidence level B- Derived from single RCT or non-radomized controlled studies
Evidence level C- Consensus opinion of expert.

23. ● When to start?
● What the guideline says ……
● Target should be <6.8 mg/dl (5-6 mg/dl)
● Available drugs-
- Xanthine oxidase inhibitors (for over producers)
- Uricosuric agents (for under excreters)
- Uricases

24. - Controlling hyperuricemia is of foremost importance as it can prevent and reverse
urate deposition
- Regarding starting of the urate lowering therapy there are two schools of thought.
Some physicians think that the first attack is the late manifestation o the disease
process. Others think that because tophi and symptomatic chronic gouty arthritis
dev. only in a few cases so premature use of this medication can be avoided.
- 2012 ACR guidelines says- Established diagnosis of gouty arthritis AND tophaceous
deposits by examination or imaging, frequent attacks (min. 2 per yr), CKD (Stage 2 or
worse), h/o urolithiasis
- <4 mg/dl is req. if multiple tophi present

25. ● Hypoxanthine Xanthine oxidase (XO) Xanthine XO Uric acid(UA)
● Indications-
- Urinary UA > 1000 mg/24 hrs
- Hyperuricemia due to HPRT synthase deficiency or PRPP
synthetase overactivity
- Uric acid nephropathy
- Nephrolithiasis
- Prophylaxis before cytolytic therapy
- Intolerance or reduced efficacy of uricosuric agents

26. ● Allopurinol-
- 100mg in morning initially
- can be increased upto 800mg
- dose should be adjusted in renal disease
- adverse effects include- TEN, vasculitis, renal failure
● Febuxostat-
- 40-80 mg once daily dose
- no adjustment required in mild to moderate renal
insufficiency

27. ● Ideal candidates are-
- < 60 yrs age
- normal renal function
- uric acid in urine < 800 mg/24 hrs
- no history of renal calculi
● Probenecid-
- 250 mg twice daily (Max 3 gm/day)
- not effective if creatinine >2 mg/dl

28. ● Benzbromarone-
- suppression of uric acid resorption via inhibition of
URAT1 (OAT)
- non-competitive inhibitor of xanthine oxidase
- 100 mg once daily
-Adverse effect – hepatotoxicity
● Lesinurad-
- recently approved in 2015 Dec. by FDA
- moderate renal impairment
- 400-600 mg/day

29. In a trial combination of Lesinurad 400 mg with Allopurinol 200-600 mg achieved a
target level of uric acid <6 mg/dl in 75% cases. Whereas Lesinurad 400 mg with
Febuxostat 40 or 80 mg led to achieving serum uric acid <5 mg/dl in 100% cases.
Harris M et al. Effect of low dose daily Aspirin on serum urate levels and urinary
excretion in patients receiving Probenecid for Gouty arthritis. J Rheumatol
27:2873,2000

30. ● The latest drugs –
1. RDEA3170 (Verinurad) :-
- URAT1 inhibitor
- equipotent to benzbromarone but 500 times more potent
than probenecid in in-vitro assays
2. Arhalofenate :-
- being developed as an insulin-sensitizer for type II
Diabetes
- found to inhibit URAT1
- completed phase II of the ongoing trial

31. ● Uric acid urate oxidase Allantoin
● Rasburicase-
- obtained from Aspergillus flavus
- 1.5 mg/ml once daily for 5 days
● Pegloticase-
- a mammalian uricase attached to polyethylene glycol
- decreases the infusion reaction
- 8 mg/ml twice weekly for one week
Infusion reactions like anaphylaxis. Indicated for those who have failed all the other therapies

32. ● An ancient affliction of joint
● One of the best understood diseases but very poorly
controlled
● Dietary restrictions are very important
● New insight into the pathogenesis has led to the progress in
the drug discovery
● Hoping that they make a positive effect on gout incidence
and prevalence in the coming years
Cause for poor control is the non- compliance of the patient to the medication, misconceptions
about the gout medications.

33. THANK YOU ALL