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Tumour necrosis factor alpha blockade is associated with sustained regression of carotid intima-media thickness for patients with active psoriatic arthritis: a 2-year pilot study
  1. Lai-Shan Tam1,
  2. Edmund K Li1,
  3. Qing Shang1,
  4. Brian Tomlinson1,
  5. Martin Li1,
  6. Ying-Ying Leung2,
  7. Woon Pang Kuan3,
  8. Lai-Wa Kwok1,
  9. Tena K Li1,
  10. Yaner Zhu1,
  11. Emily W Kun4,
  12. Gabriel Yip1,
  13. Cheuk-Man Yu1
  1. 1Department of Medicine and Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
  2. 2Department of Medicine, North District Hospital, Hong Kong, China
  3. 3Department of Rheumatology, Hospital Selayang, Kuala Lumpur, Malaysia
  4. 4Department of Medicine and Geriatrics, Tai Po Hospital, Hong Kong, China
  1. Correspondence to Dr Lai-Shan Tam, Department of Medicine and Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China; tamls_813{at}yahoo.com

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We have reported that psoriatic arthritis (PsA) patients without overt cardiovascular diseases have evidence of premature atherosclerosis as indicated by an increased carotid intima-media thickness (IMT).1 Whether an increase in IMT reflects current (but reversible) inflammation of the vessel wall rather than more permanent structural vessel changes in PsA has never been assessed. We undertook a prospective, observational study to determine whether a 12-week treatment of tumour necrosis factor alpha (TNFα) blockers may reduce IMT in patients with active PsA, and whether the changes in IMT can be sustained in patients who were continued on long-term TNFα blockers.

Twenty consecutive PsA patients with active disease were recruited to receive TNFα blockers. After 12 weeks, nine patients continued (group 1) while 11 patients discontinued TNFα blockers due to financial constraints (group 2). Twenty PsA patients who were naive to TNFα blockers were recruited as controls (group 3). Patients were prospectively followed for 2 years. IMT was measured by carotid ultrasound at baseline, 12 weeks (groups 1 and 2) and at the last visit.

At 12 weeks, a significant reduction in the maximum IMT in groups 1 and 2 and also the mean IMT in group 2 was observed (table 1). After a mean follow-up of 24.7±3.9 months, the maximum IMT continued to show significant reduction only in group 1. In contrast, the change in IMT in group 2 became statistically insignificant, while significant progression in the mean IMT was observed in group 3. There was a trend suggesting that the rate of change in the mean IMT may be different between the three groups.

Table 1

Changes in the IMT in the three groups

This is the first longitudinal study on the progression of IMT in patients with PsA. The results of this study showed that short-term TNFα blockade significantly slowed the progression of atherosclerosis in PsA patients with active disease, and further regression of the maximum IMT was possible only in patients who were continued on long-term TNFα blockers, suggesting that effective suppression of inflammation in patients with high-grade inflammation may potentially reverse early atherosclerotic lesions. We cannot exclude the possibility of IMT reduction by other potent immunosuppressants including methotrexate, as over 50% of patients in both groups 1 and 2 were on concomitant methotrexate, and methotrexate therapy has been associated with a decrease in cardiovascular disease events in patients with rheumatoid arthritis.2

The major limitation of this study included the small sample size and the open-label study design. The inclusion of patients who can afford their own payment for TNFα blockers after the first 3 months may also introduce a selection bias. The higher baseline mean and maximum IMT in group 3 was unexpected because the disease activity and inflammatory markers were lower. Nonetheless, the natural progression of this group may be higher regardless of therapy. Because of the small sample size, only maximum IMT showed significant regression in group 1 as the mean IMT values are more reproducible but are less sensitive to change, whereas the maximum IMT values are more sensitive to change but are less reproducible,3 and may be more susceptible to outliers. Based on the current finding, a future randomised study with 18 patients in each group will be required to detect a significant difference in the maximum IMT between the two groups with a power of 80% and and α value of 0.05.

Notwithstanding all the limitations, this study provides preliminary evidence supporting the hypothesis that potent immunosuppressants, including TNFα blockers, may prevent the progression of IMT in PsA by effective suppression of inflammation. Longer-term follow-up of the IMT from future randomised controlled trials of TNFα blockers in PsA patients would be warranted to confirm our findings.

Acknowledgments

The authors would also like to thank their research assistants Lorraine Tseung and Raymond Lau for their contributions in data collection and entry. The authors independently interpreted the results and made the final decision to submit the manuscript for publication.

References

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Footnotes

  • Funding This study is supported by a Chinese University research grant, a Hong Kong Arthritis and Rheumatism Foundation research grant, and an educational grant from Janssen Pharmaceutical (Hong Kong). The study drugs were provided by Janssen Pharmaceutical (Hong Kong) and Wyeth (Hong Kong), who had no role in the study design, data collection, data analysis or writing of the manuscript.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of The Chinese University of Hong Kong.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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