Heterogenous bone response to biologic DMARD therapies in rheumatoid arthritis patients and their relationship to functional indices

Abstract

Objectives: Previous studies of high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging of hand joints in patients with rheumatoid arthritis (RA) have suggested that erosion healing may occur. Our objective was to examine changes in erosion volume, joint space width (JSW), bone mineral density (BMD), and bone remodelling, and their association with clinical outcomes and measures of patient hand function.

Method: We examined 48 patients who achieved a good response to a newly initiated biologic therapy. HR-pQCT images of the dominant hands’ second and third metacarpophalangeal joints were obtained 3 and 12 months after therapy initiation. Bone erosion volume, JSW, BMD, and bone remodelling were quantified from HR-pQCT images, with improvement, no change (unchanged), or progression in these measures determined by least significant change. Disease activity and hand function measures were collected.

Results: There were no significant group changes in HR-pQCT outcomes over the 9 month period. Twenty-two patients had total erosion volumes that remained unchanged, nine showed improvement, and two progressed. The majority of JSW and BMD measures remained unchanged. There was a significant association between the baseline Health Assessment Questionnaire score and the change in minimum JSW, but no other significant associations between HR-pQCT outcomes and function were observed.

Conclusions: The vast majority of patients maintained unchanged JSW and BMD over the course of follow-up. Significant improvements in total erosion volume occurred in 27% of patients, suggesting that biologic therapies may lead to erosion healing in some patients, although this did not have an impact on self-reported and demonstrated hand function.

Acknowledgements

We thank Tessa Linkert for assistance with patient recruitment and data collection, and imaging technologists in the Centre for Mobility and Joint Health (Anne Cooke, Taryn Harris, Stephanie Kwong, and Duncan Raymond) for image acquisition.

This study was supported by the Arthritis Society [1025850, STAR-18-0189]. Salary support was provided by NSERC (SCB, MTK), T Chen Fong Post-Doctoral Fellowship (JJT), and the Arthritis Society (SLM).

Availability of data and material

Data will be made available upon reasonable request.

Code availability

Joint space width analysis scripts are available by contacting Scanco Medical AG. Erosion analysis was performed using Medical Imaging Analysis Framework (MIAF; University of Erlangen) and access is available by contacting Klaus Engelke. All Python and IPL scripts used in the bone remodelling analysis are available on the Manske Lab GitHub page: https://github.com/ManskeLab/BHS

Disclosure statement

KE is a part-time employee of Bioclinica, Inc. All other authors have no conflicts of interest to declare.

Supporting information

Additional supporting information may be found in the online version of this article.

Supplementary material. Image registration and bone remodelling analysis information: exclusions for motion artefact.

Supplementary figure S1. The relationship between the minimum JSW at baseline and

diagnosis duration.

Supplementary figure S2. The relationship between the baseline joint space volume and the baseline DAS28 score.

Supplementary figure S3. The relationship between the change in the minimum joint space width and the baseline HAQ score.

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