Kieth Need Advice – Pronto (please)

[Luke Haymond]

So after almost 4 weeks of Allo 300 mg per day I just received a 7.1 UA result (an increase from 6.3). A bit discouraged by that. The Dr. is suggesting I change to Uloric? Can you give me your opinion of that recommendation, as well as, any experience with UA level rising while increasing Allo? I’ll continue the 300 mg per day of Allo for now, but would like to act on your advice sooner than later (increase Allo, try Uloric?)

Thanks

[Keith Taylor]

Leku asked:

Can you give me your opinion of that recommendation

Uloric is manufactured and distributed by Takeda.

From Japan (needs login)

Takeda Tops Physician Honoraria Payment List in FY2013

We surveyed 19 companies that had disclosed their funding as of September 24 and for which comparable data were available for the previous year. Takeda Pharmaceutical paid over 1.9 billion yen under this category, the largest among the 19, followed by Daiichi Sankyo and Novartis Pharma. The closely watched category consists of three subcategories of ?lecture fees,? ?manuscript writing fees or supervising fees,? and ?consulting or commissioning fees?

From USA:

Dollars for Docs: Who?s On Pharma?s Top-Paid List?

Psychiatrist Jon W. Draud […] speaks or consults not only for those companies, but also for Forest Laboratories, Sanofi-Aventis, Takeda Pharmaceuticals and Wyeth Pharmaceuticals (Pfizer acquired Wyeth in October 2009)

and How Much Money Does Your Doctor Get From Medical Companies? has a search tool for doctor payments and links to the database of payments. There are hundreds of Uloric related payments from Takeda in the database. I didn’t find any for allopurinol, but I was struggling with the search tool, so there might be some.

These people might be starving, or otherwise financially challenged. Buy as much Uloric as you can to prevent further suffering. On the other hand, a significant part of my advertising revenue comes directly, or indirectly from Uloric. Stop buying it so they advertise more!

I’m conflicted. 😕

[Luke Haymond]

Ok, let’s try this again…

1) have you seen periodic “rebounds” in UA levels during Allo dosage search phase – I was expecting steady, albeit maybe unacceptably little, change in UA

2) assuming liver and kidney levels are unchanged – I’m guessing you would increase Allo and continue search for correct dosage

[Keith Taylor]

It’s great to see three data points for uric acid levels in your Gout Profile. It’s also great to see three data points for allopurinol dosage. Other gout sufferers take note – record significant gout facts in your personal gout profile. Before I analyze that data, the most significant point is that none of those levels represent safe uric acid.

Your lowest level in your profile is 6.2 on 3/17. This is theoretically good, but has very little safety margin. I’m not sure if the 6.3 in your original question is an extra data point or a typo. Either way, it reinforces the important fact that uric acid is not down to the 5mg/dL that is required.

Moving to the uric acid data analysis. For many years, I have emphasized the need to think in terms of uric acid ranges rather than absolute values. There is natural fluctuation in uric acid levels. Of course, it is impossible to know if an individual test result represents the top or bottom of your daily range, or something in between. To be certain, you would need to test through the day, every two hours. Not very practical.

It is unusual for uric acid to rise when allopurinol dose increases, but we only have limited data to work with. More tests mean better data analysis, though I must repeat that this is all academic, as we are discussing different degrees of unsafe uric acid levels. To get a true comparison between individual test results, we must consider confounding factors. Possible explanations for a rise are:

• Presence of gout flare in early tests
• Recent crystal dissolution in latest test
• Blood drawn at different time of day
• Blood drawn at different time after eating animal purines

My conclusion is that, though this rise from 6.3 to 7.1 is unusual:

1. It is within the bounds of natural fluctuation
2. As a one-off comparison, confounding factors are more likely than cause-effect

My ‘recipe’ for analyzing uric acid test results is to ignore the lowest and highest values, then plot rolling averages to identify trends. In this case, there is insufficient data to draw conclusions, so we must continue to collect data, and switch focus to the treatment plan.

A good uric acid control plan is driven by targets, and tuned by results. The long-term target for uric acid control is 5mg/dL. This might be compromised by other health conditions in a small percentage of cases, where 6mg/dL is the absolute maximum. I describe the first phase of uric acid control as ‘debulking.’ The aim of the debulking phase is to dissolve most of the old uric acid crystals that have formed throughout the body in the years of untreated excess uric acid.

Doctors have a clear mandate from rheumatologists to consider uric acid lower than 5 to resolve visible tophi. My argument is that recent DECT technology proves that pre-visible tophi are rampant in every gout sufferer. These are the uric acid crystals that cause gout flares during uric acid lowering treatment. They are dangerous, destroying joints and compromising organ health. Several studies have proved that old deposits dissolve faster when uric acid is lower than 5. Therefore, I always recommend that patients agree a lower target during the first year of allopurinol, or other uric acid lowering treatment.

I feel it’s important that patient and doctor are both very clear about dose during different phases. They need to manage a high allopurinol dose during debulking, and a suitable lifetime dose to maintain uric acid no higher than 5. There are transition (aka titration) phases before debulking is achieved, and between debulking and maintenance doses. The transition phases need blood test control and dose adjustment every 2 to 4 weeks. Maintenance testing must be at least once a year, with debulking testing somewhere in between.

So, concluding with:

2) assuming liver and kidney levels are unchanged ? I?m guessing you would increase Allo and continue search for correct dosage

You are right to mention liver function and kidney function tests. These are recommended for every gout sufferer whenever uric acid is tested. They are vital for every gout patient undergoing any form of uric acid lowering treatment.

I would first set a target uric acid level for 2015. Personally, I would go for “as low as I can get,” but you and your doctor should agree what is best for you. Clearly, 300mg allopurinol is insufficient and so you need to agree an action plan with your doctor. Beyond 2015, you can reassess your allopurinol dose to maintain gout freedom for life.

We can discuss your maintenance dose specifically at the time. In my opinion, the end of the debulking period is marked by no gout flares for 6 months during a period when uric acid is never higher than 5mg/dL. In that regard, you haven’t actually started the debulking period yet.

In simple terms: Yes! increase the allopurinol as soon as you are sure that blood tests indicate that is safe.

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