MIRROR was a 52-week randomized, double-blind trial conducted in adult patients with chronic gout refractory to conventional therapy. It evaluated the administration of KRYSTEXXA 8 mg Q2W co-administered with 15 mg oral methotrexate QW and 1 mg oral folic acid QD vs KRYSTEXXA alone.1,2

MTX AdministrationMTX Administration

*After randomization, clinicians had the ability to dose-adjust methotrexate but chose not to.

The primary endpoint was defined as the proportion of responders who maintained an sUA level of <6 mg/dL for at least 80% of the time during Month 6.2

The secondary endpoint was defined as the proportion of responders who achieved and maintained an sUA level of <6 mg/dL for at least 80% of the time during Month 12.1

IV, intravenous; MTX, methotrexate; PO, provided orally; QD, every day; QW, every week; Q2W, every 2 weeks; sUA, serum uric acid.

Trial patient characteristics

KRYSTEXXA MIRROR RCT patient population (N = 152)
PATIENT CHARACTERISTICS KRYSTEXXA WITH MTX (n = 100) KRYSTEXXA ALONE (n = 52)
Age, mean (SD) years 55.6 (12.7) 53.0 (12.1)
Male sex, n (%) 91 (91) 44 (84.6)
BMI, (mean) (SD), kg/m2 32.7 (5.6) 32.7 (7.8)
sUA, mean (SD), mg/dL 8.7 (1.6) 9.1 (1.7)
Time since 1st gout diagnosis, mean (SD), years 13.7 (10.6) 14.3 (10.8)
# of flares in 12 months prior to baseline, mean (SD) 10.6 (12.9) 11.3 (16.7)
Presence of tophi, n (%), yes 52 (52.0) 29 (55.8)
Stage 3 CKD, n (%) 33 (33.3) 16 (30.8)

BMI, body mass index; CKD, chronic kidney disease; SD, standard deviation; sUA, serum uric acid.

Review the Inclusion/Exclusion Criteria

For a nephrologist that would say, ‘Managing gout’s not my responsibility,’ I would argue that it absolutely is.

Hear how nephrologist Christopher Gisler helped one of his patients who didn’t have success on oral gout therapy.

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My name's Chris Gisler. I'm a board-certified nephrologist practicing in the Pittsburgh area. As a nephrologist, I feel that I'm responsible for the total care of my patients.

We’re already doing the best we can with chronic kidney disease, but our patients suffer from gout. There is actually a strong association between chronic kidney disease and gout... about a third of the patients that you’re taking care of have gout, most likely. It’s not just a disease of the big toe, not just a disease of the joints. We need to really consider this as a disease that’s affecting the whole body, multiple organ systems. We know that many different organs are affected, including the heart. We know that our patients with gout are at more risk for cardiovascular disease. To me, it does no good to prolong a patient’s life by managing their kidney disease if they’re absolutely miserable, right? If we treat gout, address gout, and do a better job with managing gout, we’re improving the patient’s overall functional status.

I met this patient that I had been following for chronic kidney disease. She was a bit on the obese side and so a lot of the joint pain that she complained to me about in her knees I attributed to osteoarthritis. She revealed to me that she had significant gout and actually had gone to the ER for a gout flare. We talked about it—she failed oral therapy with Allopurinol—and were able to prescribe her KRYSTEXXA. KRYSTEXXA is a biologic. As with many biologic therapies, there is a risk of anaphylaxis and infusion reactions. When we began managing her gout with KRYSTEXXA, she did have multiple flares at the beginning, which is a known effect of the gout treatment. Once she got through those first couple of treatments though, she really noticed improvement. The frequency and severity of flares were decreasing. Also, the pain she had just at baseline was markedly improved. She was able to ambulate more frequently and really was starting to get more and more of her life back. By treating with KRYSTEXXA we’re dramatically lowering the serum uric acid level, sort of draining the tub so that that serum uric acid level is zero, allowing that uric acid that was deposited into the joints to be pulled out. Many of the interventions we perform as nephrologists, patients don’t see a tangible benefit. With our patients on KRYSTEXXA, they start feeling better. I’m encouraging my patients to treat for at least 6 months. If they’re still seeing continued improvement, we’ll continue to treat. Now I do caution them that once you feel better that doesn’t necessarily mean that you are better. So, we know that in addition to flares for gout there’s also a subclinical gout. Damage is still being done to the joints even if they’re not actively flaring. And so, it’s very important to get gout under control.

I think for a nephrologist that would say, “Managing gout’s not my responsibility,” I would argue that it absolutely is. This is a disease process that we should be comfortable with. This is a disease process that kind of goes hand in hand with chronic kidney disease. Chronic kidney disease is a slow progressive disease where patients don’t necessarily see improvements. They say, “Doctor, I’m doing all the right things. I still don’t feel much better.” With gout, we can actually make interventions, so the patients come back and say they feel better. I think any time we can do something to make a patient feel better, to get them to become more active, to address an issue that they’re really concerned about, and to see marked improvement in it in a relatively short amount of time I think is really rewarding.

I'm Dr. Chris Gisler. These are our patients, and we need to take action.

Interested in how KRYSTEXXA may help reduce sUA?

Connect with the KRYSTEXXA team to discuss.

sUA, serum uric acid.

KRYSTEXXA and chronic kidney disease

KRYSTEXXA with methotrexate has been studied in patients with chronic kidney disease.1‡

In the MIRROR randomized controlled trial, 85% had eGFR more than 40 and less than 90. 

Learn about patients who might benefit from KRYSTEXXA

IMPORTANT SAFETY INFORMATION

WARNING: ANAPHYLAXIS AND INFUSION REACTIONS, G6PD DEFICIENCY ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA

  • Anaphylaxis and infusion reactions have been reported to occur during and after administration of KRYSTEXXA.
  • Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours of the infusion. Delayed hypersensitivity reactions have also been reported.
  • KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions.
  • Premedicate with antihistamines and corticosteroids and closely monitor for anaphylaxis for an appropriate period after administration of KRYSTEXXA.
  • Monitor serum uric acid levels prior to each infusion and discontinue treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.
  • Screen patients at risk for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to starting KRYSTEXXA. Hemolysis and methemoglobinemia have been reported with KRYSTEXXA in patients with G6PD deficiency. KRYSTEXXA is contraindicated in patients with G6PD deficiency.

CONTRAINDICATIONS:

  • In patients with G6PD deficiency.
  • In patients with history of serious hypersensitivity reactions, including anaphylaxis, to KRYSTEXXA or any of its components.

WARNINGS AND PRECAUTIONS

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.

ADVERSE REACTIONS

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.

INDICATION

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.

IMPORTANT SAFETY INFORMATION

WARNING: ANAPHYLAXIS AND INFUSION REACTIONS, G6PD DEFICIENCY ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA

  • Anaphylaxis and infusion reactions have been reported to occur during and after administration of KRYSTEXXA.
  • Anaphylaxis may occur with any infusion, including a first infusion, and generally manifests within 2 hours of the infusion. Delayed hypersensitivity reactions have also been reported.
  • KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis and infusion reactions.
  • Premedicate with antihistamines and corticosteroids and closely monitor for anaphylaxis for an appropriate period after administration of KRYSTEXXA.
  • Monitor serum uric acid levels prior to each infusion and discontinue treatment if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.
  • Screen patients at risk for glucose-6-phosphate dehydrogenase (G6PD) deficiency prior to starting KRYSTEXXA. Hemolysis and methemoglobinemia have been reported with KRYSTEXXA in patients with G6PD deficiency. KRYSTEXXA is contraindicated in patients with G6PD deficiency.

CONTRAINDICATIONS:

  • In patients with G6PD deficiency.
  • In patients with history of serious hypersensitivity reactions, including anaphylaxis, to KRYSTEXXA or any of its components.

WARNINGS AND PRECAUTIONS

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.

ADVERSE REACTIONS

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.

INDICATION

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.

  • KRYSTEXXA (pegloticase) [prescribing information] Horizon.
  • Data on File. Horizon, March 2022