ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 961

The Association of Biologic Drug-Levels with Infection Risk: Results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Meghna Jani1, William G Dixon1, Mark Lunt1, Diederik De Cock1, John Isaacs2, Ann Morgan3, Kath Watson1, Anthony G. Wilson4, Anne Barton5,6 and Kimme L. Hyrich1,5, 1Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, United Kingdom, 2Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom, 3Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, Great Britain, 4UCD School of Medicine and Medical Science, Conway Institute, University College Dublin, Dublin, Ireland, 5National Institute of Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom, 6Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University Of Manchester, Manchester, United Kingdom

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Date: Sunday, October 21, 2018

Session Title: 3S108 ACR Abstract: RA–Treatments II: Safety (958–963)

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

  Background/Purpose: High dose tumour necrosis factor inhibitor (TNFi) drugs are associated with an increased serious infection (SI) risk[1]. It is feasible that high biologic levels predict dose-dependent adverse events such as SI. No registries have systematically evaluated the effect of drug levels on infection risk. The objective was to assess the effect of biologic drug levels in rheumatoid arthritis (RA) patients on (i) all infections (AI) (ii) SI (infections requiring hospitalization, IV antibiotics or lead to death) Methods:

Patients recruited to both the British Society for Rheumatology Biologics Register-RA (safety data) and the Biologics in RA Genetics & Genomics Syndicate (serological samples) were included. Both are large national prospective RA cohorts. Biologic drug levels were measured at 3/6/12 months after biologic initiation and stratified as low/normal or high drug levels (HL) as per thresholds defined using concentration-effect curves for each drug. The risk of first and total infections within the first year was analysed. Events occurring on drug or within 90 days of last dose were included. The risk of an event was compared between low/normal vs. HL groups using Cox proportional-hazard models. Factors affecting both drug levels and infection risk were adjusted for in the models. Results:

703 patients (286 etanercept, 179 adalimumab, 120 certolizumab, 104 tocilizumab and 14 infliximab) had clinical data and serological samples. 74% were women, mean (SD) age 58 (12) years, on a first biologic (89%). The crude rate/1000 pyrs was 314 and 464 for AI; 54 and 76 for SI in the low/normal and HL groups respectively. The adjusted hazard ratio for AI within the first year differed significantly between the two groups with the HL group having 50 percent higher risk of AI (HR: 1.51; 95% CI: 1.14, 2.01) (table). The most common types of AI in the HL group were lower (34%) and upper (16%) respiratory tract infections, urinary tract infections (15%), skin infections including shingles (8%).

 

 

Low/

normal drug level (n=241)

High drug levels

(n=462)

All events  with follow up censored at 1 year (95% CI)

All infections (n)

63

232

Crude rate (/1000 pyrs)

314 (245, 401)

464 (408, 528) 

Unadjusted HR

Ref

1.44 (1.09, 1.91)*

Adjusted HR †

Ref

1.51 (1.14, 2.01)*

Serious infections (n)

11

38

Crude rate (/1000 pyrs)

54 (30, 98)

76 (55, 104)

Unadjusted HR

Ref

1.36 (0.70, 2.67)

Adjusted HR†

Ref

1.17 (0.58, 2.30)

First event within 1st year (95% CI)

All infections (n)

46

150

Crude rate (1000 pyrs)

229 (172, 256)

300 (256, 352)

Unadjusted HR

Ref

1.24 (0.89, 1.73)

Adjusted HR  †

Ref

1.26 (0.91, 1.78)

Serious infections (n)

6

22

Crude rate (/1000 pyrs)

29 (13, 67)

44 (28, 67)

Unadjusted HR

Ref

1.39 (0.56, 3.44)

Adjusted HR†

Ref

1.26 (0.50, 3.16)

*p<0.05 †Adjusted for age, gender, DAS score, methotrexate use

Image/graph:

All infections_drug levels_300dpi1

  Conclusion:

 RA patients with high biologic drug levels have a higher risk of infection. Monitoring drug levels may be helpful in prediction of infection. In disease remission patients with high drug levels, biologic dose tapering may lower infection risk.

References: (1)Singh JA, Cameron C et al. Lancet 2015;368;258-265

Acknowledgements: Funded by MRC CiC award & BMA Doris Hillier grant to MJ, AB, WGD, KLH. 

 

Disclosure: M. Jani, Grifols for an invited academic talk, 9; W. G. Dixon, None; M. Lunt, None; D. De Cock, None; J. Isaacs, None; A. Morgan, None; K. Watson, None; A. G. Wilson, None; A. Barton, None; K. L. Hyrich, None.

To cite this abstract in AMA style:

Jani M, Dixon WG, Lunt M, De Cock D, Isaacs J, Morgan A, Watson K, Wilson AG, Barton A, Hyrich KL. The Association of Biologic Drug-Levels with Infection Risk: Results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/the-association-of-biologic-drug-levels-with-infection-risk-results-from-the-british-society-for-rheumatology-biologics-register-for-rheumatoid-arthritis/. Accessed March 21, 2023.

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