Use of MRP8/14 in clinical practice as a predictor of outcome after methotrexate withdrawal in patients with juvenile idiopathic arthritis

Emma J Sumner; Beverley Almeida; Jason Palman; Peter Bale; Clare Heard; Dirk Holzinger; Johannes Roth; Dirk Foell; Emily Robinson; Simona Ursu; Chris Wallace; Kimberly Gilmour; Lucy R Wedderburn; Elizabeth Ralph

doi:10.1007/s10067-022-06165-4

Use of MRP8/14 in clinical practice as a predictor of outcome after methotrexate withdrawal in patients with juvenile idiopathic arthritis

Clin Rheumatol. 2022 Sep;41(9):2825-2830. doi: 10.1007/s10067-022-06165-4. Epub 2022 Apr 29.

Authors

Emma J Sumner^{1

2}, Beverley Almeida^{1

3}, Jason Palman^{1

3}, Peter Bale³, Clare Heard¹, Dirk Holzinger⁴, Johannes Roth⁵, Dirk Foell⁶, Emily Robinson^{1

2}, Simona Ursu¹, Chris Wallace^{7

8}, Kimberly Gilmour^{2

9}, Lucy R Wedderburn^{1

2

3

10}, Elizabeth Ralph^{11

12

13}

Affiliations

¹ Infection Inflammation and Rheumatology Department, University College London, Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
² NIHR BRC, Great Ormond Street Hospital for Children NHS Trust, London, UK.
³ Department of Rheumatology, Great Ormond Street Hospital for Children NHS Trust, London, UK.
⁴ Department of Paediatric Haemato-Oncology, University of Duisburg-Essen, Essen, Germany.
⁵ Institute of Immunology, University of Munster, Munster, Germany.
⁶ Department of Paediatric Rheumatology and Immunology, University Hospital Munster, Munster, Germany.
⁷ MRC Biostatistics Unit, Cambridge Biomedical Campus, Cambridge Institute of Public Health, University of Cambridge, Cambridge, UK.
⁸ Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
⁹ Department of Immunology, Great Ormond Street Hospital for Children NHS Trust, London, UK.
¹⁰ Centre for Adolescent Rheumatology Versus Arthritis at UCL, UCLH & GOSH, London, UK.
¹¹ Infection Inflammation and Rheumatology Department, University College London, Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK. e.ralph@ucl.ac.uk.
¹² NIHR BRC, Great Ormond Street Hospital for Children NHS Trust, London, UK. e.ralph@ucl.ac.uk.
¹³ Department of Immunology, Great Ormond Street Hospital for Children NHS Trust, London, UK. e.ralph@ucl.ac.uk.

Abstract

The objective of this study was to determine the effectiveness of MRP8/14 as a predictor of disease flare in patients with juvenile idiopathic arthritis (JIA) following the withdrawal of methotrexate (MTX) in a routine clinical setting. All MRP8/14 tests performed at a single centre in a 27-month period were considered for analysis. Patients were assessed against criteria for inactive disease and subsequent disease flare. Decisions on whether or not to stop treatment were recorded. MRP8/14 results were assessed in conjunction with clinical information. Clinicians were also surveyed to investigate if MRP8/14 influenced their decision to discontinue MTX where this was available at that time point. One hundred four cases met the inclusion criteria during the study period. Although there was no significant difference in flares between patients with an elevated or low MRP8/14 value, in those who stopped MTX (n = 22), no patients with a low MRP8/14 (≤ 4000 ng/ml) result flared (follow-up time 12 months). Clinicians reported that for patients with clinically inactive disease and an elevated MRP8/14 result (> 4000 ng/ml), none would advise withdrawal of MTX. Low MRP8/14 was interpreted favourably when considering stopping MTX treatment in patients with JIA. Implementation of MRP8/14 testing has changed clinical practice at this centre. However, the observation that some patients in our cohort who had an elevated MRP8/14 value did not flare after stopping MTX for non-disease-related reasons highlights the need for further biomarkers to predict the risk of flare off medication in JIA and aid clinicians in treatment decisions. Key Points • First study of serum MRP8/14 measurement in clinical practice to inform treatment decisions in patients with JIA. • No patients with a low MRP8/14 test result went on to suffer a disease flare in 12 months of follow follow-up. • Further biomarkers are needed to predict the risk of flare off medication in JIA and treatment decisions.

Keywords: Juvenile idiopathic arthritis; Methotrexate; Outcomes research.

MeSH terms

Antirheumatic Agents* / therapeutic use
Arthritis, Juvenile* / drug therapy
Biomarkers
Humans
Methotrexate / therapeutic use
Symptom Flare Up
Treatment Outcome

Substances

Antirheumatic Agents
Biomarkers
Methotrexate

Abstract

MeSH terms

Substances

Grants and funding