Impact of Dose Tapering of Tumor Necrosis Factor Inhibitor on Radiographic Progression in Ankylosing Spondylitis

PLoS One. 2016 Dec 29;11(12):e0168958. doi: 10.1371/journal.pone.0168958. eCollection 2016.

Abstract

Objective: To investigate the impact of dose reduction of tumor necrosis factor inhibitor (TNFi) on radiographic progression in ankylosing spondylitis (AS).

Methods: One hundred and sixty-five patients treated with etanercept or adalimumab were selected from a consecutive single-center observational cohort based on the availability of radiographs at baseline and after two- and/or four-years of follow up. Radiographs were assessed by two blinded readers using the modified Stokes AS Spinal Score (mSASSS). Radiographic progression in patients treated with standard-dose TNFi (standard-dose group, n = 49) was compared with patients whose dosage was tapered during the treatment (tapering group, n = 116) using linear mixed models.

Results: Baseline characteristics between two groups were comparable except for higher BASDAI (7.1 vs. 6.3, p = 0.003) in the standard-dose group. At two years after the treatment, mean dose quotient (S.D.) of the tapering group was 0.59 (0.17). During follow up, rate of radiographic progression in overall patients was 0.90 mSASSS units/year. Radiographic progression over time between the two groups was similar at the entire group level. However, in the subgroup of patients with baseline syndesmophytes, progression occurred significantly faster in the tapering group after the adjustment for baseline status (1.23 vs. 1.72 mSASSS units/year, p = 0.023). Results were consistent when radiographic progression was assessed by the number of newly developed syndesmophytes (0.52 vs. 0.73/year, p = 0.047). Sensitivity analysis after multiple imputation of missing radiographs also showed similar results.

Conclusion: A dose tapering strategy of TNFi is associated with more rapid radiographic progression in AS patients who have syndesmophytes at baseline.

Publication types

  • Observational Study

MeSH terms

  • Adalimumab / pharmacology*
  • Adalimumab / therapeutic use
  • Adult
  • Cohort Studies
  • Disease Progression*
  • Dose-Response Relationship, Drug
  • Etanercept / pharmacology*
  • Etanercept / therapeutic use
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Radiography
  • Spondylitis, Ankylosing / diagnostic imaging*
  • Spondylitis, Ankylosing / drug therapy*
  • Time Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Tumor Necrosis Factor-alpha
  • Adalimumab
  • Etanercept

Grants and funding

This study was supportive by a grant from Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1277). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.