gout 2 Flashcards
Back to the Patient Case
Mo (he/him) is a 53 year old regular patient who is describing an acute onset
of red, swollen, and painful big toe. He states the pain began in the middle of
the night and it hurts so badly he is having difficulty ambulating.
* PMHx: T2DM
* SHx: nonsmoker, 1-2 glasses of wine/week
* ROS: 5’10”, 275lbs
* Otherwise unremarkable
* Medications:
* ECASA 81mg daily
* Metformin 850mg BID
Could his condition be treated by drug therapy?
ok
Approach to Treatment: Chronic
● KEY is to prevent recurrent attacks
● Recommend prophylactic therapy if:
○ ³2 flares/year, regardless of SUA
○ ³ 1 tophus on clinical exam or imaging
○ Radiographic damage (any modality) attributable to gout
● Consider prophylactic therapy with first flare if:
○ CKD ³Stage 3
○ SUA >535 µmol/L
○ History of urolithiasis
● When is the ideal time to initiate ULT?
○ Traditionally: Recommended to NOT start prophylaxis during an acute
gout flare
■ Does not improve symptoms, speed up resolution, or reduce inflammation
by starting during a flare
○ BUT Controversial!
■ Wait ~2 weeks after gout flare? Initiate during acute flare?
○ 2020 ACR Guidelines:
■ ULT may be started during acute flare, as long as effective anti- inflammatory management has been instituted
● Ongoing prophylactic therapy should NOT be interrupted during an
acute flare
● Must use an anti-inflammatory to prevent acute flare during initiation
If someone is on allopurinol therapy or Febuxostat therapy already and they have a flare. It’s really important that they don’t stop that chronic therapy to treat the flair and then think about restarting
So once someone is on uric acid lowering therapy, even if they flare, occasionally, that therapy should remain consistent.
● Should we be using a treat-to-target approach for gout?
○ Controversy ongoing!
■ Should we be managing gout in a similar fashion as RA, given it is a chronic inflammatory condition associated with cardiovascular risk factors, morbidity,and mortality?
EULAR 2017 “Treat to Target”
* target SUA <360µmol/L for all patients
with gout (ACR 2020 too!)
* target SUA <300µmol/L for those with
tophi or frequent flares until clinical
remission is attained
ACP 2017 “Treat to Avoid Symptoms”
* do not monitor SUA
* use a dose of urate lowering therapy if
necessary that prevents acute flares
following discussion of risks, benefits,
and costs
rheumatology folks said, we recognize this as a chronic systemic inflammatory condition. Cure is our goal. And we know that if we target serum uric acid less than 360, that we’re going to decrease long-term complications with, with gout, including cardiovascular events. The American College of Physicians said, we need to treat to avoid symptoms. Less people should be on this type of therapy. We shouldn’t be monitoring serum uric acid.
Interpreted differently
Non-Pharmacologic Therapy
● Patient Education
○ Role of uric acid excess
■ D/C any non-essential medications that contribute to ↑SUA
○ Importance of adherence (SUA lowering therapies/measures)
○ Importance of prompt self-treatment of future flares
● Weight loss for obese patients
○ Healthy diet and exercise
● Screening for CVD & risk factors
○ CKD, HTN, DM, lipids, smoking
● Stay well hydrated
● Purine restricted diet
○ No RCTs exist and observational data
shows low adherence
v One serving meat or
fish/day (vs. more)
v Wine instead of beer or spirits
v Weight loss
Correlated
with fewer
flares
Uric Acid Lowering Therapy
● Treat to Target:
○ SUA <360 µmol/L (but >180 µmol/L)
○ SUA <300 µmol/L in severe gout (tophi, frequent flares)
- Some guidelines will recommend a target of less than 300 if people have those TO phi.
● Therapeutic Approach
○ Xanthine Oxidase Inhibitors (first line)
■ decrease synthesis of uric acid
● allopurinol (classic)
● febuxostat (novel)
○ Uricosuric Agents (if refractory)
■ increase renal excretion of uric acid
● probenecid, sulfinpyrazone
● losartan, fenofibrate
Xanthine Oxidase Inhibitors: MOA
block xanthine oxidase changing hypoxanthine to xanthine and xanthine to uric acid
Efficacy:
● Effective in vast majority of patients (85%)
○ Long-term adherence is low
● However, 5% unable to tolerate it due to AE
Allopurinol
dose
Dose: range 100-800mg/d (average 300mg)
○ Needs to be titrated to an effective dose & for tolerability
■ Titrate to SUA <360 μmol/L
■ Limit risk of acute flares and serious adverse effects
○ Start at 100 mg/d (50 mg/d if CrCl <30 ml/min)
■ Titrate in 50-100 mg increments every 2-5 weeks
■ Usually takes about 3-6 months to reach target dose
■ Divide doses if >300 mg/d for GI tolerability
○ Dose adjust if:
■ Reduced renal function – traditionally, but not evidence based
■ Any drug interactions
Allopurinol
● Adverse Effects:
○ Mild: skin rash, GI upset, diarrhea, headache, urticaria, leukopenia
○ Serious: Allopurinol Hypersensitivity Syndrome (AHS)
■ Symptoms:
● Rash: maculopapular, pruritic; TEN, EM, SJS;
● Hepatitis or interstitial nephritis; and
● Fever or eosinophilia or leukocytosis
■ Occurs 1:1000 and results in up to 25% mortality!
■ Risks:
● Thiazides, high initial dose, CKD (perhaps DM, female sex)
● HLA-B*5801 allele: genetic marker of risk
○ Consider testing in patients with higher prevalence: those of Southeast Asian (Korean, Han Chinese, Thai) descent and Black patients
Allopurinol: Monitoring
Effectiveness:
● Reduction/elimination of
acute gout flares
● Reduction/resolution of
tophi (slowly, over time)
● SUA at regular intervals
when titrating (q2-6wks)
○ Once stable, q6mo to
monitor adherence
Safety:
● CBC/diff, SCr, BUN, ALT
○ baseline, while titrating; then
q6-12mo
● Pruritis, rash – early signs of
serious skin reactions
● If renally impaired:
○ watch ALT and eosinophils
more closely
XOI Drug Interaction
Blocks primary route
of metabolism
to inactive form!
Leading to increased “efficacy” =
life threatening
leukopenia!!!
Febuxostat (Uloric®)
● Dose: 80mg po daily
○ Doses from 40-240mg/d have been studied
■ as dose increases, see greater reductions in SUA but risk acute gout flare at higher doses
○ No dose adjustment if CrCl >30mL/min
■ Use not recommended (not studied) if CrCl <30mL/min
● Efficacy
○ Is newer better? Does febuxostat offer any advantages over allopurinol in
preventing gout?
Febuxostat Efficacy:
febuxostat is not better than allopurinolf or prventing gout and has higher rate of gout flares
it should only be considered in patients who experienced a serious AE w/ allopurinol
Febuxostat Safety: CARES v FAST
concern that it might actually increase the risk of cardiovascular events. I
Febuxostat was no worse. Then allopurinol was. However, in the care study, they actually saw a statistically significant increase in cardiovascular death and any death
what we saw there is that there wasn’t this statistically significant increase.
Febuxostat
MOA
AE
● Same MOA as allopurinol BUT unique structure
○ Alternative in 2% of patients who experience rash on allopurinol
■ Though allopurinol desensitization is also an alternative (if minor)
○ Mild: rash, nausea, arthralgias, LFT elevations
○ May be slightly better tolerated in short term, but evens out over long term
■ Have been case reports of hypersensitivity & serious skin reactions (DRESS) in patients
with history of allopurinol reactions
more safe with respect to those serious adverse events. So patients who have had an allopurinol hypersensitivity syndrome may have a serious rash with febuxostat as well. But many patients will tolerate Febuxostat if they don’t tolerate allopurinol.
allopurinol stil 1st (for now)
Febuxostat
monitoring
● Monitor:
○ SCr, LFTs at baseline, periodically thereafter (up to q6-12mo)
○ Signs/symptoms of hypersensitivity or severe skin reactions
