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Effect modification by contextual factors of urate-lowering therapy on serum urate in people with gout: A systematic review with meta-regression analysis.
Semin Arthritis Rheum. 2022 10; 56:152049.SA

Abstract

OBJECTIVE

To synthesize evidence of the effect of contextual factors (CFs) on efficacy of urate-lowering therapy (ULT) on serum urate (SU) as outcome in gout patients.

METHODS

Randomised controlled trials (RCTs) from (updated) Cochrane reviews were the starting point. RCTs were included if they explored the role of any CF on efficacy of ULT on SU in gout patients. For CFs with sufficient data (i.e. ≥3 trials), a mixed-effects meta-regression analysis was performed with trial and comparison as random effects, whereas specific CFs were modelled as fixed factors.

RESULTS

Eight RCTs were included. Effect modification by CFs was explored for age, sex, race, renal function, cardiovascular comorbidity, tophi, thiazide-diuretic use, and previous ULT use. Crude data stratified by renal function were available for four trials (36 randomised comparisons), and suitable for meta-analysis. Pooled estimates revealed that gout patients with a normal, mildly-, or moderately impaired renal function were consistently more likely to achieve SU target with ULT compared to control. Among RCTs comparing ULT to placebo (30 comparisons), effects of ULT on achieving SU target were not statistically different for those with normal (OR:66.87;[11.39-392.75]) compared to mildly (OR:28.54;[5.11-159.46]) and moderately (OR:21.45;[3.20-143.64]) impaired renal function, but seemed lower in those with severely impaired (OR:9.13;[0.96-86.97]) renal function. Data were insufficient to draw conclusions on effect modification by other CFs.

CONCLUSION

Few RCTs report stratified analyses exploring the role of CFs. ULT seemed effective in reaching the SU target in all levels of renal function, though severely impaired renal function appeared to render a slight disadvantage.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Kampe RT
Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Center, P.O. Box 5800, Maastricht, AZ 6202, the Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands; Department of Rheumatology, VieCuri Medical Center, Venlo, the Netherlands. Electronic address: r.tekampe@maastrichtuniversity.nl.
Nielsen SM
Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Denmark.
Hotea I
Department of Rheumatology, University of Medicine and Pharmacy, Cluj-Napoca, Romania.
van Durme C
Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Center, P.O. Box 5800, Maastricht, AZ 6202, the Netherlands; Centre Hospitalier Chrétien, Liège, Belgium.
Christensen R
Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Denmark.
Boonen A
Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Center, P.O. Box 5800, Maastricht, AZ 6202, the Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands.

MeSH

GoutGout SuppressantsHumansRegression AnalysisUric Acid

Pub Type(s)

Journal Article
Meta-Analysis
Systematic Review
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35728446

Citation

Kampe, Ritch Te, et al. "Effect Modification By Contextual Factors of Urate-lowering Therapy On Serum Urate in People With Gout: a Systematic Review With Meta-regression Analysis." Seminars in Arthritis and Rheumatism, vol. 56, 2022, p. 152049.
Kampe RT, Nielsen SM, Hotea I, et al. Effect modification by contextual factors of urate-lowering therapy on serum urate in people with gout: A systematic review with meta-regression analysis. Semin Arthritis Rheum. 2022;56:152049.
Kampe, R. T., Nielsen, S. M., Hotea, I., van Durme, C., Christensen, R., & Boonen, A. (2022). Effect modification by contextual factors of urate-lowering therapy on serum urate in people with gout: A systematic review with meta-regression analysis. Seminars in Arthritis and Rheumatism, 56, 152049. https://doi.org/10.1016/j.semarthrit.2022.152049
Kampe RT, et al. Effect Modification By Contextual Factors of Urate-lowering Therapy On Serum Urate in People With Gout: a Systematic Review With Meta-regression Analysis. Semin Arthritis Rheum. 2022;56:152049. PubMed PMID: 35728446.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect modification by contextual factors of urate-lowering therapy on serum urate in people with gout: A systematic review with meta-regression analysis. AU - Kampe,Ritch Te, AU - Nielsen,Sabrina Mai, AU - Hotea,Ioana, AU - van Durme,Caroline, AU - Christensen,Robin, AU - Boonen,Annelies, Y1 - 2022/06/15/ PY - 2022/03/10/received PY - 2022/05/31/revised PY - 2022/06/10/accepted PY - 2022/6/22/pubmed PY - 2022/9/9/medline PY - 2022/6/21/entrez KW - Contextual factors KW - Effect modification KW - Gout KW - Renal function KW - Urate-lowering therapy SP - 152049 EP - 152049 JF - Seminars in arthritis and rheumatism JO - Semin Arthritis Rheum VL - 56 N2 - OBJECTIVE: To synthesize evidence of the effect of contextual factors (CFs) on efficacy of urate-lowering therapy (ULT) on serum urate (SU) as outcome in gout patients. METHODS: Randomised controlled trials (RCTs) from (updated) Cochrane reviews were the starting point. RCTs were included if they explored the role of any CF on efficacy of ULT on SU in gout patients. For CFs with sufficient data (i.e. ≥3 trials), a mixed-effects meta-regression analysis was performed with trial and comparison as random effects, whereas specific CFs were modelled as fixed factors. RESULTS: Eight RCTs were included. Effect modification by CFs was explored for age, sex, race, renal function, cardiovascular comorbidity, tophi, thiazide-diuretic use, and previous ULT use. Crude data stratified by renal function were available for four trials (36 randomised comparisons), and suitable for meta-analysis. Pooled estimates revealed that gout patients with a normal, mildly-, or moderately impaired renal function were consistently more likely to achieve SU target with ULT compared to control. Among RCTs comparing ULT to placebo (30 comparisons), effects of ULT on achieving SU target were not statistically different for those with normal (OR:66.87;[11.39-392.75]) compared to mildly (OR:28.54;[5.11-159.46]) and moderately (OR:21.45;[3.20-143.64]) impaired renal function, but seemed lower in those with severely impaired (OR:9.13;[0.96-86.97]) renal function. Data were insufficient to draw conclusions on effect modification by other CFs. CONCLUSION: Few RCTs report stratified analyses exploring the role of CFs. ULT seemed effective in reaching the SU target in all levels of renal function, though severely impaired renal function appeared to render a slight disadvantage. SN - 1532-866X UR - https://www.unboundmedicine.com/medline/citation/35728446/Effect_modification_by_contextual_factors_of_urate_lowering_therapy_on_serum_urate_in_people_with_gout:_A_systematic_review_with_meta_regression_analysis_ DB - PRIME DP - Unbound Medicine ER -