[Chapter Title]: CKD and Gout
Hello, my name is Dr. Jessica Coleman, and I'm a board-certified nephrologist practicing in Beaufort, South
Carolina. I've been practicing for about 11 years. Like most nephrologists, I have a close relationship with
most of my patients.
I even treat some patients and their family members as well; in some cases, they feel like my family.
Studies show that patients with moderate-to-severe CKD have a 10-fold increase in gout prevalence.1 Based on experiences in my clinic, I believe the numbers may be even higher than that. The prevalence rates we see in practice make the official data feel underestimated. I believe that the reason for this is that physicians simply aren't looking for it.
At least 15% of my patients have gout. About 5% to 10% of them have uncontrolled gout. In a typical week, I see about 90 patients and about 10% to 20% of them have a serum uric acid or sUA level of greater than 6 milligrams per deciliter.
Patients with gout are typically prescribed oral urate-lowering therapies or ULTs such as allopurinol and febuxostat.2-4 For many patients, their gout is still uncontrolled while taking oral ULTs and they need another option.
A lot of our patients will make changes in their diet and lifestyle to avoid a gout flare. Of course, if their gout becomes uncontrolled, none of that really matters.13-15
We know that oral ULTs are not very effective when it comes to uncontrolled gout. In addition, some patients cannot tolerate oral ULTs.2-5
Uncontrolled gout is a chronic and systemic disease that can really impact our patient's health. Urate crystals can deposit almost anywhere, in bones, joints, and vital organs such as the heart and kidney.16-22
We also know that, even if diet and lifestyle changes can help manage gout flares, they cannot treat the underlying causes of the disease.13,14 One of the things I often tell my patients is that even with the best diet control, they can only move the needle within 1 milligram per deciliter.13,14 So, if a patient is starting in the double digits, like 10 milligrams per deciliter, for example, they are likely never going to get their sUA goal with diet and lifestyle changes alone.
At that point, their treatment becomes reactive as opposed to proactive. When the patient has another flare, we react by prescribing colchicine or prednisone. This is a cycle that can repeat for years, and obviously this strategy is underwhelming and not ideal for their overall quality of life.
[Chapter Title]: Identifying Uncontrolled Gout in Patients with CKD
I've seen patients with uncontrolled gout experience various symptoms, painful flares, tophi under the skin,
and pain and stiffness in their joints.5 We also see a lot of patients with lower back pain in my practice.
In my experience, this tends to be one presentation of the disease, but it's often underappreciated as
uncontrolled gout.
Tophi are not always visible in patients, which can make identifying the disease more challenging. It's important for us as nephrologists to remember that uncontrolled gout can present differently.6,7
One of my patients with uncontrolled gout had a very atypical presentation, a pronounced limp and terrible lower back pain. She certainly did not have tophi, and that is something that unfortunately happens with a lot of our patients. Pain simply becomes their new normal, and they learn to adjust to it. Often if they don't have visible tophi, uncontrolled gout can be missed. My patient did have uncontrolled gout with painful flares, and by identifying it, we were able to put her on treatment, and she was able to get back to her everyday life.
I believe that uncontrolled gout is underdiagnosed. Sometimes patients can be misdiagnosed with old age arthritis instead of gouty arthritis. The simple reality is that if we don't go looking for uncontrolled gout, we don't find it.
As nephrologists, we see multiple, often serious health conditions along with other factors that can be challenging. Some are in the hospital; some have transportation issues. Often, their other coexisting conditions take higher priority, and we may not get the chance to identify their uncontrolled gout.
That's why it's important to include the appropriate testing and ask the correct questions. Checking serum uric acid levels routinely is critical when it comes to identifying uncontrolled gout, and it should be a standard test in every nephrology office. If a patient's blood work is only done during an acute gout flare, the sUA level may be low due to transient increases in uric acid excretion in the urine during a flare. In that case, a single sUA result may not be truly reflective of the whole-body uric acid load.23,24 That's why I test my patients routinely. Adding sUA to the rest of the patient's routine blood work doesn't add any additional lab work burden, because they're already going to get their blood work done.
Knowing how to interpret the data is just as important as having the data in the first place. Common comorbidities like hypertension, BMI greater than 30, or type 2 diabetes may be a sign to assess your patients for gout. If my patient's sUA level is at or above 6 milligrams per deciliter and they are on the appropriate maximum dose of oral ULT but have two or more flares per year or present with non-resolving tophi, I diagnose them with uncontrolled gout.5 When they reach maximum dosage on allopurinol, if their sUA is not normalizing, then I prescribe KRYSTEXXA.
KRYSTEXXA is the first FDA-approved treatment for this disease, and it has been on the market for over 14 years.8
Based on my experience with KRYSTEXXA, I trust it, so I prescribe it to my uncontrolled gout patients, and I empower my nurse practitioners to prescribe it as well. I also rely on my medical assistants in preparing our patients for treatment with KRYSTEXXA; they know the patient's individual needs and concerns.
Nephrologists tend to be very busy. Some nephrology practices identify and treat uncontrolled gout, but in general, I think it can fall victim to the fact that there are too many cooks in the kitchen. For example, the general practitioner may assume a specialist is handling the disease. We, as nephrologists, may think that a rheumatologist is addressing it, and vice versa.
That's why it's important for nephrologists to take ownership of uncontrolled gout. We should be looking for it. We should absolutely feel comfortable identifying it. This disease can significantly impact a patient's lifestyle and helping them address their uncontrolled gout can help them get back to their everyday lives.
[Chapter Title]: KRYSTEXXA and Patients with CKD
Introducing KRYSTEXXA is an important step of the process. Once my team and I identify a patient who could
benefit from KRYSTEXXA, we start the conversation. I tell my patients, "You have been on this medication for
years now, and it's no longer doing as good of a job as we need it to do. Let's talk about improving your
experience and hopefully preventing future gout flares. At this point in time, I think the next appropriate
step is to go on infusion therapy, specifically KRYSTEXXA”.
I introduce it by specifying that this treatment's active ingredient, pegloticase, is the only treatment recommended by the American College of Rheumatology or ACR Guidelines for uncontrolled gout.5,8 I explain that KRYSTEXXA works differently than oral ULTs because it's an infused biologic that converts urate into allantoin which is excreted by the kidneys. I assure them that KRYSTEXXA has been studied in patients with CKD.8
Finally, I tell patients that they will receive the infusion every two weeks. In a relatively short period of time, 6 to 12 months, they may be able to significantly improve their symptoms and see results.8 Patients can be intimidated by the infusion aspect of treatment at first, but once we review the safety profile of KRYSTEXXA and the difference it may make in their lives, they tend to warm up to the idea. Some patients have such debilitating flares and/or tophi that they're willing to try other options that may help them feel better. 8 My patients typically have someone in their life who has been treated with an IV infusion medication. I try to equate it to experiences that they have seen in friends or family members. This makes it a little more relatable for them.
Typically, patients see their sUA levels drop quickly and significantly leading to improvement in their signs and symptoms which reassures them that the treatment is working. 8
If a patient is worried about side effects, like infusion reactions, I explain to them that there is a protocol of pre-infusion medication to address that and go over the safety of the treatment.8,25 I also find patient stories to be very powerful. I like to show my patients the difference that KRYSTEXXA has made in real patients' lives.
I encourage patients to call us if they experience a mobilization flare which is something that happens to patients usually within the first three months of treatment, and it is a sign that KRYSTEXXA is working. KRYSTEXXA dissolves the urate crystals that have been accumulating and allows them to be eliminated in the urine in the form of allantoin.8 I make sure that patients have medicine on hand so that if they experience a mobilization flare, they have meds to take immediately.
My patients have had great experiences with the patient support program Amgen By Your Side. The program's patient access liaisons, or PALs, can answer questions on the insurance process and connect our patients to other KRYSTEXXA patients. And they can also help identify infusion locations for the patient and schedule their appointments.
In MIRROR RCT, 71% of patients on KRYSTEXXA with methotrexate achieved the primary endpoint of patient response at Month 6.8
Among patients who had tophi at baseline, 54% of patients achieved a 100% resolution of at least 1 target tophus at Month 12.8
KRYSTEXXA has an established safety profile. It has been studied in patients with CKD and doesn’t require a dose adjustment.8
[Chapter Title]: Real Patient Story
There was a patient whose debilitating acute flare I
had to treat prior to prescribing KRYSTEXXA, and her sUA levels had been elevated for years. She had
multiple comorbidities prior to developing uncontrolled gout. She was taking oral ULTs for several years,
both allopurinol and febuxostat, and slowly over years, we were able to bring her sUA lower, but it was
still above goal. It wasn't low enough to prevent urate build up and eventually, she developed tophi. She
was hospitalized twice for severe acute flares and gout-related complications. I said to myself, "This
treatment isn't doing enough." I had since been introduced to KRYSTEXXA, and my patients had success with
it, so I made the recommendation. The difference was substantial. Her tophi are improving, her sUA levels
are well below six, and she's doing great.
I'm very confident in prescribing KRYSTEXXA to my patients with uncontrolled gout. I have seen the difference it can make in my patients' lives, and I am happy that I can help them get there. I've had patients who felt trapped by their disease and through effective treatment, I'm able to see them get back to what they love.
On the other hand, I have patients who have two or more flares in a year, sometimes three to four flares in a year and an sUA level higher than 6 milligrams per deciliter and they are not aware of the urate deposit building up in their body. Being able to diagnose their uncontrolled gout and treat them feels very rewarding.
KRYSTEXXA can be a very effective solution for uncontrolled gout patients who are allergic to oral ULTs or patients who were advised to stop taking oral ULTs. Left untreated, uncontrolled gout can cause systemic damage to the joints and bones, with urate deposition in the vital organs like the kidneys and heart.16-22
[Chapter Title]: Ownership of Uncontrolled Gout
As nephrologists, we are responsible for our patients' overall health. KRYSTEXXA can really help their
uncontrolled gout and may limit further damage. I think about the patient I mentioned earlier who struggled
to lower their sUA on oral ULTs, and at a certain point, you just have to say to yourself, "I've got to take
control of this disease."
Improving somebody's uncontrolled gout symptoms is incredibly rewarding, and that's not something that we, as nephrologists, get to do quite frequently. Seeing my patients’ progress made me a believer in KRYSTEXXA.
[Chapter Title]: A Final Thought
We all went into this profession presumably to first do no
harm. Sometimes I have to remind folks that by overlooking a disease state, by not addressing a disease
state, at times that can be construed as doing harm, right? By not allowing patients access to appropriate
treatment options, we may, actually unfortunately, do harm by virtue of keeping a treatment option away from
a patient who could otherwise experience a really significant change in their life.
When you take a patient who has had even infrequent gout flares, even just two a year, but when you take a patient from having gout flares to not having gout flares, it's incredibly rewarding, incredibly significant, and the patient has something tangible that they can hold onto, that they can see how you have impacted their lives.
References:
Connect with the KRYSTEXXA team to discuss.
There are several steps that will help prepare patients for infusion and ensure proper administration of KRYSTEXXA.
How can reducing antidrug antibodies improve patient response?
Occupation:
Bus driver
52-year-old with stage 4 CKD; 3 flares in the last year and no visible tophi
Actor portrayal, not actual patient.
Occupation:
Dental hygienist
45-year-old with stage 3b CKD; 3 flares in the last year and 1 small tophus on her left hand for the past 2 years
Actor portrayal, not actual patient.
Occupation:
Former EMT
Diagnosed with gout over
20 years ago
Real patient.
CKD, chronic kidney disease.
Gout Flares: An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy, including KRYSTEXXA. Gout flare prophylaxis with a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended starting at least 1 week before initiation of KRYSTEXXA therapy and lasting at least 6 months, unless medically contraindicated or not tolerated.
Congestive Heart Failure: KRYSTEXXA has not been formally studied in patients with congestive heart failure, but some patients in the pre-marketing placebo-controlled clinical trials experienced exacerbation. Exercise caution in patients who have congestive heart failure and monitor patients closely following infusion.
The most commonly reported adverse reactions (≥5%) are:
KRYSTEXXA co-administration with methotrexate trial:
KRYSTEXXA with methotrexate: gout flares, arthralgia, COVID-19, nausea, and fatigue; KRYSTEXXA alone: gout flares, arthralgia, COVID-19, nausea, fatigue, infusion reaction, pain in extremity, hypertension, and vomiting.
KRYSTEXXA pre-marketing placebo-controlled trials:
gout flares, infusion reactions, nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis, and vomiting.
KRYSTEXXA® (pegloticase) is indicated for the treatment of chronic gout in adult patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated.
Limitations of Use: KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia.
Please see Full Prescribing Information, including Boxed Warning.
