Evidence map›Paper›PMID 42734877›Full record

ReviewBioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy2026

Beyond the Prevention of Anti-drug Antibody Formation with Uricase Therapy: Mechanistic Roles of DMARDs in Modifying Gout Flare Risk.

Ted R Mikuls, Tuhina Neogi, Angelo Gaffo

Abstract readReview
PubMed Publisher
In one paragraph

Review in BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Ted R MikulsUniversity of Nebraska Medical Center and VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA. tmikuls@unmc.edu.ORCID http://orcid.org/0000-0002-0897-2272
Tuhina NeogiBoston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9515-1711
Angelo GaffoUniversity of Alabama at Birmingham and the Birmingham VA Medical Center, Birmingham, AL, USA.ORCID http://orcid.org/0000-0001-7365-7212

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Disease-modifying antirheumatic drugs (DMARDs) are immune-modifying agents that have shown efficacy in improving response rates and reducing infusion reactions associated with uricase therapy for uncontrolled gout by inhibiting anti-drug antibody (ADA) formation. However, increased gout flare rates following initiation of uricase therapy remain a concern, impacting patient quality of life and treatment adherence. Gout flares are an acute inflammatory reaction to monosodium urate crystals, driven by inflammasome activation. As such, it is possible that DMARDs could impact gout flare risk. In this hypothesis-generating narrative review, we have synthesized mechanistic data investigating the effects of the DMARDs methotrexate, mycophenolate mofetil, azathioprine, leflunomide, and sirolimus on mechanisms involved in gout flare such as NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activation. The mechanisms by which DMARDs inhibit ADA formation appear to be distinct from those that may affect gout flares, but these may exist in balance with one another to form a distinct pharmacological profile for each agent. Paradoxically, preclinical evidence suggests that DMARDs may sometimes induce NLRP3 inflammasome activation, particularly at higher doses. We suggest that individual DMARDs' effect on inflammatory pathways relevant to gout flare may vary depending on the pathophysiological context and differences in their pharmacological profiles. Therefore, the inflammatory consequences of combining DMARDs with uricase therapy are likely to be specific to the individual agent. Understanding the mechanistic profile of each DMARD is key to optimizing both immunogenicity management and flare outcomes in patients receiving uricase therapy for uncontrolled gout.

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.