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Doppler ultrasound impacts response to intravenous tocilizumab in rheumatoid arthritis patients

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Abstract

Objective

Within rheumatoid arthritis (RA) patients treated with intravenous tocilizumab (IV-TCZ), it is unclear if power Doppler ultrasonography (PDUS) can predict future clinical response. This study sought to determine if baseline PDUS or its early changes can predict 12-week and 24-week disease activity outcomes, and quantify the need for dose escalation (4 to 8 mg/kg).

Methods

Fifty-four RA patients starting IV-TCZ were evaluated at baseline, 4, 6, 12, 16, and 24 weeks using 34-joint PDUS (US34-PDUS), clinical disease activity index (CDAI), 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR), ACR 20/50/70, health assessment questionnaire-disability index (HAQ-DI), and PDUS 20/50/70, a novel measure. Logistic regression models evaluated the predictive utility of US34-PDUS of DAS28-ESR response after adjusting for covariates.

Results

Ninety-four percent of patients required dose escalation to 8 mg/kg. US34-PDUS, CDAI, and DAS28-ESR improved significantly over 24 weeks (p < 0.001). Baseline PDUS and 12-week PDUS change correlated with CDAI at 24 weeks (p < 0.05). Logistic regression demonstrated baseline US34-PDUS was independently associated with DAS28-ESR ≥ 1.2 response, even after adjusting for baseline DAS28-ESR (p = 0.03). CDAI, DAS28-ESR, and their components increased across PDUS 20/50/70 categories; however, HAQ-DI did not.

Conclusion

RA patients treated with IV-TCZ for 24 weeks demonstrated significant improvement, and baseline/early changes in PDUS were predictive of later clinical response. The PDUS 20/50/70 measure is a novel metric of response. This study suggests that IV-TCZ 4 mg/kg may not be sufficient to attain low RA disease activity at 12 weeks, in RA patients with moderate to severe disease (DAS28 ≥ 4.4 and US34-PDUS ≥ 10).

Trial registration

ClinicalTrials.gov NCT01717859

Key Points

• Over 90% of RA patients with baseline DAS28-ESR ≥ 4.4 and PDUS34 ≥ 10 required intravenous tocilizumab dose escalation from 4 to 8 mg/kg at 12 weeks.

• Reduction in power Doppler ultrasonography (US34-PDUS) scores correlate with DAS28-ESR and CDAI over 24 weeks in rheumatoid arthritis patients with moderate to severe disease activity.

• Baseline US34-PDUS predicts future improvements in clinical disease activity outcomes, independent of baseline DAS28-ESR.

• Clinical response measures, DAS28-ESR and CDAI, improved across US34-PDUS 20/50/70 categories, while patient-reported outcomes did not.

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Funding

This work was supported by investigator-initiated grants from Genentech [ML28542].

Author information

Author notes

  1. Gurjit S. Kaeley and Veena K. Ranganath contributed equally to this work.

Authors and Affiliations

  1. Division of Rheumatology, David Geffen School of Medicine, University of California, Los Angeles, 1000 Veteran Avenue, Box 32-59, Los Angeles, CA, 90024, USA

    Nicolette T. Morris, William Martin, Tanaz A. Kermani, Geraldine Navarro, Mihaela B. Taylor & Veena K. Ranganath

  2. Department of Medicine Statistics Core, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA

    Jenny Brook & David Elashoff

  3. Division of Rheumatology, Cedars Sinai Medical Center, Los Angeles, CA, USA

    Ami Ben-Artzi

  4. Healthcare Partners, Los Angeles, CA, USA

    Lynette Avedikian-Tatosyan

  5. Division of Rheumatology, Harbor-UCLA Medical Center, Los Angeles, CA, USA

    George Karpouzas

  6. University of California, Irvine, School of Medicine, Irvine, CA, USA

    Himakar Nagam

  7. Division of Rheumatology, School of Medicine, University of California, San Diego, San Diego, CA, USA

    Soo Choi

  8. Division of Rheumatology and Clinical Immunology, College of Medicine, University of Florida, Jacksonville, Jacksonville, FL, USA

    Gurjit S. Kaeley

Authors
  1. Nicolette T. Morris
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  2. Jenny Brook
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  3. Ami Ben-Artzi
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  11. Mihaela B. Taylor
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  12. David Elashoff
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  13. Gurjit S. Kaeley
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  14. Veena K. Ranganath
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Contributions

Study design: NTM, VKR, GSK, and DAE. Data acquisition: GSK, ABA, JB, VKR, WM, TAK, LAT, GK, GN, SC, MBT. Data analysis and interpretation: NTM, GSK, JB, DAE, HN, and VKR. Drafting manuscript: NTM, GSK, JB, DAE, HN, and VKR. Final version approval: NTM, JB, ABA, WM, TAK, LAT, GK, HN, GN, MBT, DAE, GSK, and VKR.

Corresponding author

Correspondence to Veena K. Ranganath.

Ethics declarations

Ethical approval

The study was approved by institutional review boards (IRB #12–001547 and WIRB #1148917).

Consent to participate

Obtained for all patients with UCLA IRB approved informed consent form.

Consent to publication

Obtained for all patients with UCLA IRB approved informed consent form.

Conflict of interest

VKR has received investigator-initiated grants from Genentech, Pfizer, Mallinckrodt, BMS, and consulting for BMS and Gilead. The remaining authors have declared no conflicts of interest.

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Morris, N.T., Brook, J., Ben-Artzi, A. et al. Doppler ultrasound impacts response to intravenous tocilizumab in rheumatoid arthritis patients. Clin Rheumatol 40, 5055–5065 (2021). https://doi.org/10.1007/s10067-021-05857-7

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  • DOI: https://doi.org/10.1007/s10067-021-05857-7

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