Uricase Medication with Methotrexate

Uricase Medication with Methotrexate

This is my review of 2 similar uricase medication studies. In which I will explain the key points for gout patients. So this is for people who are concerned about gout that cannot be treated with standard uric acid treatments. Because it helps you discuss your uric acid concerns with health professionals. In the hope that you can be more engaged with your doctor’s treatment plan.

Citation for Uricase Medication

This is a GoutPal review of 2 similar studies:

  1. Albert, John A., Tony Hosey, and Brian LaMoreaux. "Increased Efficacy and Tolerability of Pegloticase in Patients With Uncontrolled Gout Co-Treated With Methotrexate: A Retrospective Study." Rheumatology and Therapy 7, no. 3 (2020): 639-648.
  2. Botson, John K., John RP Tesser, Ralph Bennett, Howard M. Kenney, Paul M. Peloso, Katie Obermeyer, Brian LaMoreaux, Michael E. Weinblatt, and Jeff Peterson. "Pegloticase in combination with methotrexate in patients with uncontrolled gout: A multicenter, open-label study (MIRROR)." The Journal of Rheumatology (2020).

At the time of writing, neither study has been cited by other studies.

Uricase Medication Purpose

Uricase is an enzyme that converts uric acid to allantoin in many animals. But it is absent in humans. However, uricase medication (pegloticase) has been developed for gout patients who cannot tolerate standard uric acid treatments.

Unfortunately, pegloticase is limited in practice due to antibodies that negate the treatment in some patients. So the response rate from uricase medication alone is typically 42%.

Pegloticase (pegylated recombinant uricase enzyme), a medication approved by the United States Food and Drug Administration (FDA) for uncontrolled gout, converts uric acid to readily excretable allantoin and is highly effective in lowering sUA [(serum Uric Acid) uric acid in the blood]. In fact, pegloticase has been shown to rapidly resolve tophi [lumps of uric acid crystals] in patients who respond to therapy (i.e., maintain sUA below 6 mg/dl). However, the proportion of patients who maintained a therapeutic response (sUA < 6 mg/dl) during treatment months 3 and 6 was only 42%. Additionally, approximately one-quarter of patients experience an infusion reaction in the absence of pre-infusion uric acid monitoring. Studies have associated the development of anti-drug antibodies with both loss of efficacy (accelerated drug clearance) and infusion reactions.

Jargon-free Facts

In this jargon-free review I present the key facts from the original study. Replacing jargon with terms more familiar to unqualified gout sufferers. Note that my selection of jargon terms might not match yours. So please ask in the feedback form near the end of the page if you need clarification.

Uricase Medication Key Facts

These are the key facts from the studies:

  • The first study reports a success rate of 80% with pegloticase and methotrexate combination. Compared to the standard 42% of pegloticase alone.
  • The second study has a similar improvement of 78.6% (11/14) compared to 42%.
  • Both studies report that methotrexate is well tolerated.

Uricase Medication Other Facts

Both studies refer to ongoing clinical trials that will investigate the combination of uricase medication with methotrexate more thoroughly.

Uricase Medication Conclusions

The effectiveness of pegloticase as uricase medication is almost doubled when combined with methotrexate.

Pegloticase (pegylated uricase) is an FDA-approved medication that is highly effective in lowering sUA by converting uric acid to allantoin, which is readily excreted by the kidneys. However, clinical studies have shown that only 42% of patients maintain sUA below 6.0 mg/dL over 6 months of pegloticase therapy, with 26% of patients having infusion-related reactions (IRs) in the absence of uric acid monitoring during treatment. Both loss of efficacy and IRs have been attributed to development of anti-drug antibodies (ADAs) that accelerate pegloticase clearance. […] In current methotrexate/pegloticase case series, the proportion of responders (based on each study’s definition) was 100% (10/10 patients), 100% (7/7 patients), and 80% (8/10 patients), all of which were higher than the 42% rate observed in clinical trials.

Combination Uricase Medication
Combination Uricase Medication

Cited By

Uricase for Fast Uric Acid Control
Uricase is an enzyme to get rid of uric acid. Humans don’t have it. See uricase-based gout treatment that removes uric acid the fastest way.

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Uricase Medication Vocabulary

  • sUA (serum Uric Acid)

    ⇢ uric acid in the blood

  • tophus (plural = tophi)

    ⇢ lump of uric acid crystals

Original Abstracts (Conclusions only)

Study 1:

Methotrexate/pegloticase co-therapy resulted in a higher responder rate than the established 42% with pegloticase alone. Therefore, methotrexate/pegloticase co-therapy may safely allow more patients to benefit from a full treatment course, likely through ADA [Anti-Drug Antibody] attenuation.

Study 2:

In this study, an increased proportion of patients maintained therapeutic response at 6 months when treated concomitantly with methotrexate and pegloticase when compared to the previously reported 42% using pegloticase alone. These results support the need for a randomized study of methotrexate or placebo with pegloticase to validate these open label findings.