I am amused that in a country recognized internationally for its high prevalence of gout (yes, I’m referring to the Philippines!), there has only been ONE gout guideline. But other nations and groups have produced several iterations of recommendations. Case in point, EULAR released last month its second version of gout guidelines – this time employing the GRADE approach in evaluating the evidence. But how does it compare to the Philippine Guidelines in 2008 (which also used GRADE) and the 2012 ACR Recommendations?
The 2016 EULAR consists of three overarching principles and 11 final recommendations. If you’re after specifics it would be best to read the full article here.
The first interesting part of this guideline are its two overarching principles which deal with patient education and screening for co-morbid conditions in gout. This is probably the first group that I’ve come across that emphasized the importance of educating patients about their disease. It’s even quite specific in enumerating what should be discussed:
- Availability of Effective Treatments
- Dealing with co-morbid conditions (like hypertension, CKD, etc.)
- Principles of treating acute flares and LIFELONG lowering of serum uric acid.
This the puts a premium on what we discuss with our patients. And probably, from now on, we would consider management incomplete when education is not one of the given interventions.
It also advises us to screen (and treat) patients for the following:
- Renal impairment
- Cardiovascular disease – coronary artery disease, heart failure, stroke, peripheral artery disease
It emphasizes the integral part of treating these co-morbid conditions as it may significantly affect our management of gout. Hence, doctors managing gout should also know how to manage these other conditions.
The third overarching principle focuses on diet and lifestyle changes. Again we see the instructions to avoid alcholic beverages and sugar sweetened beverages (another reason to support sin tax on SSBs), limit intake of meat and sea food and lose weight. Intake of dairy products and cherries were also advised as it was shown to reduce incidence of flares but without impact on SUA levels. (I think it’s only that Philippine CPG that recommends hydration as part of non-pharmacologic interventions).
EULAR, like the ACR and PRA, also didn’t place a hierarchy on which was the treatment of choice for acute gout. Again, we are told to tailor therapy based on pre-existing illnesses, prior response and patient preference. There are differences in the recommendations for colchicine (1 mg followed by 0.5mg after 1 hour) and steroids (prednisone 30-35mg/day for 5 days; no mention of tapering) administration. There is also a provision to combine agents when with severe attacks and polyarthritis. IL-1 blocking agents are recommended for conditions when colchicine, NSAIDs and steroids can’t be given (except for curent infections for which anti-IL-1 are also contraindicated). Again, i don’t see ACTH being considered as part of acute gout treatment – which I believe should be – just before anti-IL-1.
For flare prophylaxis, colchicine at 0.5-1 mg/day is recommended during the first 6 months of urate lowering therapy (ULT). Do note that it just indicates 6 months since starting ULT – with no mention of whether there was a flare of gout during the period or how long the target SUA has been achieved. On this, the EULAR departs from what ACR and PRA advices on prophylaxis duration. Caution was advised when using colchicine in the setting of severe renal impairment and concomitant statin therapy due to the increased risk of neuromuscular toxicity. I remember coming across a guideline advising us to refrain from using colchicine when creatinine clearance was <= 10 ml/min or if on dialysis (as colchicine is non-dialyzable). Low dose NSAIDs were recommended as an alternative to colchicine should it be contraindiacted. There was no mention of steroids for prophylaxis unlike that of the ACR.
EULAR didn’t make a strong recommendation on when to initiate ULT following a flare of gout. It’s common practice among Pinoy rheumas to wait for 7-10 days after flare resolution to minimize the chances of having another flare when starting ULT.
However, three things were surprising about the recommendations concerning ULT. First, is the recommendation to start ULT after the first attack of gout (and not wait for the third one or wait until there are >2 attacks/year). This is aside from the other indications such as recurrent attacks, presence of tophi and nephrolithiases and urate arthropathy. Second is the additional indications introduced by the paper:
- Gout at age <40 years
- Serum uric acid levels ≥8 mg/dl (Although, standard IM textbooks already include this)
- Presence of renal impairment, hypertension, ischemic heart disease and heart failure as co-morbid conditions.
And lastly, is the return to a conservative approach when using allopurinol in the background of decreased renal function. I had thought that the principle of “treat to target” in gout had killed this notion of having a maximum allopurinol dose based on renal function. EULAR advocates its return citing concerns over severe cutaneous adverse reactions (SCARs) which include SJS and TENS. With ACR 2012, I believed using a low starting dose (50mg every 2-3 days) and low titration dose (increasing by 50mg every titration) were all that was needed when dealing with patients with severe renal impairment. This is despite data suggesting that there will be more patients unable to reach their target SUA (which was the same with ACR) on a renal function based Allopurinol dosing system. Fortunately, the saving grace was the instruction to shift to febuxostat should patients be unable to reach their targets based on that dosing system. There was no advise, however, on how to use febuxostat in severe renal impairment. For which, I refer you to my previous post on the matter which is posted here.
The choice of allopurinol as the first line ULT by EULAR is not surprising. Cost effectiveness studies would support its routine use in gout. We have to remember that febuxostat prices start at roughly US$2 a piece in Western countries. In the Philippines, generic febuxostat prices start at an equivalent to US$0.50 (I’ve tried it on my patients and works just as nicely). ButI believe, given our local situation (Allopurinol is included in the Philippine National Formulary while febuxostat is not. Hence, the former is available in government hospitals and health centers and the latter can only be bought through private pharmacies), we should still remain skilled in using it for our patients with gout.
I’ve yet to encounter a recommendation for combining allopurinol with febuxostat for lowering SUA (but why do I encounter patients placed on such). So please, if maximum doses of either allopurinol or febuxostat aren’t enough to reach target SUA, the next step, as recommended by both ACR and EULAR, would be to add a uricosuric and NOT combine the two.
Pegloticase is once again mentioned as last resort for those unable to achieve target SUA on usual ULTs.
Now, back to my earlier comment about not having updates to the local practice guidelines. As part of the technical review group that made the first one, I can vouch that such an endeavor is demanding of both time and resources. There were attempts to update the guideline between 2012-2015 but then work was surpassed by the release of gout guidelines by several other groups (ACR, the 3E Initiative and BSR). Other agents (anti-IL-1 agents, pegloticase and lenisurad) while both interesting and exciting are not locally available and there’s no news whether it would be coming to the country. And save for febuxostat, the use of combination treatments and a different target SUA for complicated gout, the core of gout management can be found in the 2008 Philippine Clinical Practice Guidelines for Uncomplicated Gout which I’d like to believe remains relevant to this time.