Preventing and treating acute gout attacks across the clinical spectrum: A roundtable discussion

NSAIDs: SPECIAL CONSIDERATIONS FOR USE

Dr. Mandell: Let’s drill down on the use of the specific classes of drugs, starting with NSAIDs. Larry made the point that NSAIDs should be used at high doses for acute gout attacks. What else is worth noting about the dosing and use of NSAIDs in this setting?

Dr. Sundy: In addition to that distinction between analgesic and anti-inflammatory dosing, it’s important that patients be told to treat at the appropriate dose intervals for whichever NSAID is chosen so that the anti-inflammatory benefit is maintained. I generally recommend that patients continue on that dosing regimen until they have substantial symptom improvement, at which point they can begin to back off, but that’s generally a 7- to 10-day treatment course, and typically closer to 10 days. Finally, I’m quick to use proton pump inhibitors or some sort of gastroprotective regimen with most patients that I start on NSAIDs in this setting.

Dr. Mandell: Your point about duration of therapy bears emphasizing. A common mistake with the use of NSAIDs is that they’re stopped too soon out of an understandable concern about their toxicity. Often they’re stopped when symptoms are still present, which means the attack hasn’t really resolved, and so it comes back. I tell patients to wait until their attack is completely gone, continue for a few days longer, and then stop the NSAID at that point.

Dr. Edwards: If we look at the natural course of disease, a patient’s first four to six gout attacks tend to be a bit shorter in duration, in the range of 5 to 7 days. As recurrent attacks occur over the decades, they tend to get more drawn out, lasting perhaps a couple or few weeks. We want treatment to at least cover the anticipated period of the natural attack since we’re not doing anything profound to the disease process itself, except perhaps with an IL-1 inhibitor. For instance, a typical treatment in emergency departments is an intramuscular injection of ketorolac. That may make patients feel good for the next 24 or 36 hours, but they’ll have a resumption of their acute attack at that point. I generally stick to 2 weeks as a reasonable treatment period. I might shorten that for a patient with diabetes in whom I have to use steroids or for a patient with congestive heart failure that I needed to put on an NSAID, but I generally try to cover patients with anti-inflammatory therapy for a couple of weeks.

Dr. Mandell: Your point about intramuscular ketorolac is important. A single shot is not likely to resolve the attack, and the intramuscular route will not ameliorate the gastric toxicity of this drug. Those are two common misperceptions.

What about the COX-2-selective NSAIDs? There’s only one that’s still marketed in the United States, celecoxib, but what’s your sense of these drugs as a class in terms of efficacy for treating gout?

Dr. Sundy: I think they’re effective. Only one COX-2 inhibitor, etoricoxib, has been studied in clinical trials for acute gout, and it’s not available in the United States, but I think the class as a whole is a reasonable choice. That’s especially true since the course of treatment is only 7 to 14 days. Even so, it’s still reasonable to use some gastric protection when giving celecoxib, as it does no harm and can add some reassurance. As with other NSAIDs, dosing of celecoxib for acute gout is higher than for other typical uses in the drug’s labeling.

Dr. Edwards: Yes, when I use celecoxib for acute gout I use 400 mg every 12 hours for the first 2 days and then take it down to 200 mg every 12 hours for the remainder of the treatment period.

Dr. Mandell: And the COX-2-selective NSAIDs do adversely affect renal function.

Dr. Simkin: One thing that troubles me when we talk about dosage for any of our agents is the large individual variation we encounter. I don’t think there’s a patient population with a wider variation of body sizes than the gout population. We see enormous patients with metabolic syndrome and several large joints, and we see frail elderly patients who have a single small joint affected. In fact, in addition to body size, the size of the joints involved can tell us a lot about the amount of inflammation we’re dealing with. Someone with two knees and an ankle affected is probably different from someone who has just a great toe affected. In light of these variables and so many others that come into play, such as age and comorbidities, I’m hesitant to recommend any particular dose because I try to make adjustments. Of course, there are no data that cover all these variables.

Dr. Mandell: But would you agree with the generality that high doses—higher than those we typically use for other musculoskeletal pains—are warranted in treating acute gout?

Dr. Simkin: Yes, but a high dose for a small elderly woman is different from a high dose for a young man who’s quite large.

Dr. Sundy: This sensitivity to individual variation can also apply to duration of therapy. As we noted, it’s not uncommon for veteran gout patients to find that starting treatment early—within 24 or 48 hours—may be sufficient to tamp down their symptoms, yet that’s an observation that is developed only over time in an individual patient. So it’s not a recommendation, but many patients will do fine with that. In those situations, I may not be so adamant about the need to continue treatment for a full 10 or 14 days.

STEROIDS: SPECIAL CONSIDERATIONS FOR USE

Dr. Mandell: Let’s move to corticosteroids. A very common treatment used for acute gout is a tapered-dose regimen like the Medrol Dosepak (blister-pack) formulation of methylprednisolone. What strikes me is that this is a one-size-fits-all formulation, yet you’ve all just argued that there’s no one-size-fits-all approach. What are your thoughts?

Dr. Edwards: The Medrol Dosepak contains 21 4-mg tablets of methylprednisolone to be taken over the course of 6 days. Six tablets are taken the first day, and then one fewer tablet is taken each successive day through day 6. An obvious potential drawback is that the patient is off of medicine after 6 days, though that will be enough for some patients if they start treatment promptly.

I do use the Medrol Dosepak, and I always have patients fill a prescription ahead of time so that it’s available for quick initiation when they start to have their next attack. I instruct them to avoid storing it in a hot place, such as a car, but that it can be stored for up to 5 years at room temperature. Most of my patients like this approach, and if they do well with it they’re good about getting a new refill in advance of their next attack. This is a pretty handy way of letting patients be in charge of their attacks. If it doesn’t work and their symptoms continue, they call me and I’ll see them promptly.

A different approach is more appropriate for patients whose attacks tend to be more recalcitrant, perhaps because they’ve had gout for a long time or have bulky disease with lots of tophi. In those cases I’ll go with a steroid regimen that’s essentially double what a Medrol Dosepak would be—namely, prednisone 30 mg for the first 2 days then tapered down by 5 mg every other day. As Peter said, this approach would be overwhelming to a frail 82-year-old woman with a single tophus in her distal interphalangeal joint, but it tends to work well for a more typical 50-year-old obese male gout patient.

Dr. Sundy: I do some of the same things you describe, though my background in allergy has accustomed me to the steroid burst, so I’ll tend to use a dose of about 0.5 to 1.0 mg/kg/day for 4 or 5 days and then try to taper rapidly over another 2 to 4 days. I’m curious whether you think methylprednisolone offers advantages over prednisone.

Dr. Edwards: There are a few patients—roughly 5% to 15% of the population, according to various studies—who have trouble converting prednisone to its active form in their liver because they’re missing an enzyme. So I tend to use methylprednisolone since it has a benefit in that small segment of the population, but it otherwise doesn’t offer anything special beyond the convenient packaging that we discussed.

Dr. Mandell: I think convenience is the major factor. The blister-pack preparations are useful for patients who get confused with tapering. For patients who can make adjustments based on their symptoms, I find those personalized adjustments to be better than just giving them an absolute number of pills.

Dr. Pile: This issue of dosing duration is very important for generalists; just listening to your schedules is very instructive for me. I think a lot of nonrheumatologists, myself included, are inclined to use a one-size-fits-all approach. The mistake that I’ve been most apt to make, apparently, is using an insufficient duration of therapy. I’ve tended to use 40 mg prednisone for 5 or 6 days and then to stop rather than tapering the dose.

Dr. Mandell: From the cost perspective, steroids seem to be a very cost-effective option. The Medrol Dosepak, as a branded product, costs a bit more. Similarly, generic NSAIDs are inexpensive. There has been some feeling that nongeneric NSAIDs may offer advantages over generic NSAIDs, but I don’t know of any published evidence to support that. What are your thoughts?

Dr. Edwards: I agree with you. There has been this folklore about indomethacin and, before that, phenylbutazone being rather remarkable and specific drugs for gout. That hasn’t been borne out by the data, and virtually all of the NSAIDs work fairly comparably.