Effects of secukinumab on bone mineral density and bone turnover biomarkers in patients with ankylosing spondylitis: 2-year data from a phase 3 study, MEASURE 1

Abstract

Background: Axial spondyloarthritis including ankylosing spondylitis (AS) is characterized by chronic inflammation and new bone formation in the axial skeleton. On the other hand, bone loss, osteoporosis and an increased risk of vertebral fractures is known to frequently occur in AS. In the MEASURE 1 study, the clinically efficacious interleukin-17A inhibitor secukinumab was shown to have limited radiographic progression through 4 years in patients with active AS. Here we present a post hoc analysis to evaluate the effect of secukinumab on bone mineral density (BMD) and bone turnover biomarkers over 2 years in this study.

Methods: BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine, total hip, and femoral neck. Spinal radiographs performed at baseline and Week 104 were assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and analyzed in relation to BMD change, considering baseline syndesmophytes. Bone turnover biomarkers were assessed at baseline and at Weeks 52 or 104.

Results: Among 104 patients included in this analysis, 66% were male, with a mean (SD) age of 40.4 (12.3) years. In postmenopausal women and men ≥50 years of age (T-score), the proportion of patients having normal BMD at baseline and Week 104 were 54.5%/54.5% (lumbar spine), 31.6%/55.6% (total hip), and 42.1%/44.4% (femoral neck). Similarly, at baseline, the proportion of patients with osteopenia/osteoporosis was 31.8%/13.6% (lumbar spine), 57.9%/10.5% (total hip), 42.1%/15.8% (femoral neck), and 36.4%/9.1% (lumbar spine), 44.4%/0% (total hip) and 55.6%/0% (femoral neck) at Week 104, respectively. In premenopausal women and men < 50 years of age (Z-score), the proportion of patients having BMD below the expected range for age at baseline and Week 104 were 25.0%/21.2% (lumbar spine), 11.3%/17.8% (total hip), and 9.9%/8.9% (femoral neck). In relation to mSASSS change scores ≥2 over 2 years, the increase in lumbar spine BMD was not related to radiographic progression and syndesmophyte formation. No significant changes were observed in the bone turnover markers over time.

Conclusion: The high proportion of AS patients with diminished BMD was confirmed in this study. An increase of BMD in the lumbar spine after 2 years of secukinumab treatment in patients with AS was found that was probably unrelated to radiographic progression. No relevant effects of secukinumab on bone turnover biomarkers were documented.

Trial registration: MEASURE 1 (post hoc analysis) Clinicaltrials.gov, NCT01358175 ; Registered, 23 May 2011.

Keywords: Ankylosing spondylitis; Bone mineral density; Bone turnover biomarkers; Osteopenia; Osteoporosis; Secukinumab; Vertebral fractures.

Conflict of interest statement

JB: Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB, Eli Lilly consultant for: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB, Eli Lilly and received speakers bureau fees from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB pharma, Eli Lilly.

BB: Grant/research support from: Kinemed, Extendicare Foundation, Lilly, GE/Lunar and MSD; consultant for: GE/Lunar, Gilead, Theramex, UCB; received speakers bureau fees from UCB, MSD, Biogen, Sanofi Genzyme; Travel support from Janssen, UCB, Gilead, AbbVie.

XB: Grant/research support from: AbbVie, Novartis, Consultant for: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB.

LSG: Grant/research support from: Novartis, Pfizer and UCB, Consultant for: AbbVie, Eli Lilly, GSK, Novartis and UCB.

BP: Employee of Novartis and owns Novartis stock.

EQF: Employee of Novartis and owns Novartis stock.

SH: Employee of Novartis and owns Novartis stock.

© 2021. The Author(s).

Figures

Fig. 1

Normal BMD, Osteopenia, and Osteoporosis Rates in Postmenopausal Women and Men ≥50 years of age through Week 104. Data presented as observed. Normal BMD, T-score ≥ − 1.0; Osteopenia, − 1.0 > T-score > − 2.5; and Osteoporosis, T-score ≤ − 2.5. N, total number of patients; n, number of evaluable patients

Fig. 2

BMD Below and Within Expected Range in Premenopausal Women and Men  − 2.0, and below the expected range for age (‘Below Range’) = Z score ≤ − 2.0. BMD, bone mineral density; N, total number of patients; n, number of evaluable patients

Fig. 3

Bone turnover biomarkers course over time for highest and lowest quartile subgroups (at baseline). Symbol 1 – lowest quartile group of parameter at baseline. Symbol 2 – highest quartile group of parameter at baseline. For each subgroup: The box represents the upper and lower quartiles and the whiskers (10th and 90th percentiles) represents the minimum and maximum values. The center horizontal line represents the median and * represents the mean. Circles outside the boxes represent outliers

Fig. 4

Scatter plot of change in lumbar spine BMD and mSASSS in patients with/without baseline syndesmophytes. BMD, bone mineral density; mSASSS, modified Stoke Ankylosing Spondylitis Spine Score. Horizontal line indicates change in the lumbar spine BMD of zero, and vertical line is an indicator of change in mSASSS of 2