Does C-reactive protein predict time to recovery and benefit from oseltamivir treatment in primary care patients with influenza-like illness? A randomized controlled trial secondary analysis

Nicolay Jonassen Harbin; Karin Rystedt; Morten Lindbaek; Ruta Radzeviciene; Johan Westin; Ronny Gunnarsson; Christopher C Butler; Alike W van der Velden; Theo J Verheij; Pär-Daniel Sundvall

doi:10.1080/02813432.2021.2006482

Does C-reactive protein predict time to recovery and benefit from oseltamivir treatment in primary care patients with influenza-like illness? A randomized controlled trial secondary analysis

Scand J Prim Health Care. 2021 Dec;39(4):527-532. doi: 10.1080/02813432.2021.2006482. Epub 2021 Dec 1.

Authors

Nicolay Jonassen Harbin¹, Karin Rystedt^{2

3

4

5}, Morten Lindbaek¹, Ruta Radzeviciene⁶, Johan Westin⁷, Ronny Gunnarsson^{2

3

4}, Christopher C Butler⁸, Alike W van der Velden⁹, Theo J Verheij⁹, Pär-Daniel Sundvall^{2

3

4}

Affiliations

¹ Antibiotic Center for Primary Care, Department of General Practice, Institute of Health and Society, University of Oslo, Oslo, Norway.
² Research, Education, Development and Innovation, Primary Health Care, Region Västra Götaland, Sweden.
³ General Practice/Family Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ Centre for Antibiotic Resistance Research (CARe) at University of Gothenburg, Gothenburg, Sweden.
⁵ Region Västra Götaland, Närhälsan Stenstorp vårdcentral, Stenstorp, Sweden.
⁶ Mano Seimos gydytojas, Klaipeda, Lithuania.
⁷ Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
⁸ Department of Primary Care Health Services, University of Oxford, Radcliffe Observatory Quarter, Oxford, UK.
⁹ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.

Abstract

Objective: Recovery time and treatment effect of oseltamivir in influenza-like illness (ILI) differs between patient groups. A point-of-care test to better predict ILI duration and identify patients who are most likely to benefit from oseltamivir treatment would aid prescribing decisions in primary care. This study aimed to investigate whether a C-reactive protein (CRP) concentration of ≥30 mg/L can predict (1) ILI disease duration, and (2) which patients are most likely to benefit from oseltamivir treatment.

Design: Secondary analysis of randomized controlled trial data.

Setting: Primary care in Lithuania, Sweden and Norway during three consecutive influenza seasons 2016-2018.

Subjects: A total of 277 ILI patients aged one year or older and symptom duration of ≤72 h.

Main outcome measures: Capillary blood CRP concentration at baseline, and ILI recovery time defined as having 'returned to usual daily activity' with residual symptoms minimally interfering.

Results: At baseline, 20% (55/277) had CRP concentrations ≥30mg/L (range 0-210). CRP concentration ≥30 mg/L was not associated with recovery time (adjusted hazards ratio (HR) 0.80: 95% CI 0.50-1.3; p = 0.33). Interaction analysis of CRP concentration ≥30 mg/L and oseltamivir treatment did not identify which patients benefit more from oseltamivir treatment (adjusted HR 0.69: 95% CI 0.37-1.3; p = 0.23).

Conclusion: There was no association between CRP concentration of ≥30 mg/L and recovery time from ILI. Furthermore, CRP could not predict which ILI patients benefit more from oseltamivir treatment. Hence, we do not recommend CRP testing for predicting ILI recovery time or identifying patients who will receive particular benefit from oseltamivir treatment.Key PointsPredicting disease course of influenza-like illness (ILI), and identifying which patients benefit from oseltamivir treatment is a challenge for physicians.• There was no association between CRP concentration at baseline and recovery time in patients consulting with ILI in primary care.• There was no association between CRP concentration at baseline and benefit from oseltamivir treatment.• We, therefore, do not recommend CRP testing for predicting recovery time or in decision-making concerning oseltamivir prescribing in ILI patients.

Keywords: C-reactive protein; antiviral treatment; influenza-like illness; primary health care; recovery time; respiratory tract infections.

Publication types

Randomized Controlled Trial

MeSH terms

Antiviral Agents / therapeutic use
C-Reactive Protein
Humans
Influenza, Human* / drug therapy
Oseltamivir* / therapeutic use
Primary Health Care

Substances

Antiviral Agents
Oseltamivir
C-Reactive Protein

Grants and funding

The ALIC⁴E study was supported by the European Commission FP7 Programme. The Healthcare Committee, Region Västra Götaland, Sweden, partially funded the Swedish part of the study. The Antibiotic Centre for primary Care, University of Oslo partially funded the Norwegian part of the study.