postmenopausal osteoporosis; abaloparatide; number needed to treat; ACTIVE trial; fracture risk reduction
Abstract :
[en] Abaloparatide (ABL) is a 34-amino acid peptide designed to be a selective activator of the parathyroid hormone receptor type 1 signaling pathway. In the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE), subcutaneous ABL reduced the risk of new vertebral, nonvertebral, clinical, and major osteoporotic fracture compared with placebo and of major osteoporotic fracture compared with teriparatide. To further evaluate the effectiveness of ABL, we calculated the number needed to treat (NNT) to prevent one fracture using ACTIVE data. To estimate the potential effectiveness of ABL in populations at higher fracture risk than in ACTIVE, we calculated NNT for vertebral fracture using reference populations from historical placebo-controlled trials, assuming an 86% relative risk reduction in vertebral fracture with ABL treatment as observed in ACTIVE. NNT was calculated as the reciprocal of the absolute risk reduction in ACTIVE. The projected NNT for ABL in other populations was calculated based on incidence rate (IR) for vertebral fractures in the placebo arms of the FREEDOM (placebo IR 7.2%), FIT-1 (placebo IR 15.0%), and FIT-2 (placebo IR 3.8%) trials. NNT for ABL in ACTIVE
was 28 for vertebral, 55 for nonvertebral, 37 for clinical, and 34 for major osteoporotic fracture. NNT for these fracture types for teriparatide in ACTIVE were 30, 92, 59, and 75, respectively. Using placebo IRs from FREEDOM, FIT-1, and FIT-2, projected NNTs for vertebral fracture with ABL were 17, 8, and 31. These data are useful for further evaluating ABL for the
treatment of osteoporosis in postmenopausal women.
Disciplines :
General & internal medicine
Author, co-author :
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Hattersley, G.
Williams, G
Hu, M.Y.
Fitzpatrick, L.A.
Lewiecki, E.M.
Language :
English
Title :
Abaloparatide is an effective treatment option for postmenopausal osteoporosis: review of the number needed to treat compared with teriparatide.
Hattersley G, Dean T, Corbin BA, Bahar H, Gardella TJ (2016) Binding selectivity of abaloparatide for PTH-type-1-receptor conformations and effects on downstream signaling. Endocrinology 157(1):141–149
Esbrit P, Herrera S, Portal-Núñez S, Nogués X, Díez-Pérez A (2016) Parathyroid hormone-related protein analogs as osteoporosis therapies. Calcif Tissue Int 98(4):359–369
Bahar H, Gallacher K, Downall J, Nelson CA, Shomali M, Hattersley G (2016) Six weeks of daily abaloparatide treatment increased vertebral and femoral bone mineral density, microarchitecture and strength in ovariectomized osteopenic rats. Calcif Tissue Int 99(5):489–499
Leder BZ, O’Dea LS, Zanchetta JR, Kumar P, Banks K, McKay K, Lyttle CR, Hattersley G (2015) Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 100(2):697–706
Miller PD, Hattersley G, Riis BJ, Williams GC, Lau E, Russo LA, Alexandersen P, Zerbini CA, Hu MY, Harris AG, Fitzpatrick LA, Cosman F, Christiansen C, for the ACTIVE Study Investigators (2016) Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA 316(7):722–733
Varela A, Chouinard L, Lesage E, Smith SY, Hattersley G (2017) One year of abaloparatide, a selective activator of the PTH1 receptor, increased bone formation and bone mass in osteopenic ovariectomized rats without increasing bone resorption. J Bone Miner Res 32(1):24–33
Varela A, Chouinard L, Lesage E, Guldberg R, Smith SY, Kostenuik PJ, Hattersley G (2017) One year of abaloparatide, a selective peptide activator of the PTH1 receptor, increased bone mass and strength in ovariectomized rats. Bone 95:143–150
Moreira CA, Fitzpatrick LA, Wang Y, Recker RR (2017) Effects of abaloparatide-SC (BA058) on bone histology and histomorphometry: the ACTIVE phase 3 trial. Bone 97:314–319
Laupacis A, Sackett DL, Roberts RS (1988) An assessment of clinically useful measures of the consequences of treatment. N Engl J Med 318(26):1728–1733
Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C, for the FREEDOM Trial (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361(8):756–765
Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE, for the Fracture Intervention Trial Research Group (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348(9041):1535–1541
Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ, for the Fracture Intervention Trial Research Group (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 280(24):2077–2082
Cranney A, Guyatt G, Griffith L, Wells G, Tugwell P, Rosen C, Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group (2002) Meta-analyses of therapies for postmenopausal osteoporosis. IX: summary of meta-analyses of therapies for postmenopausal osteoporosis. Endocr Rev 23(4):570–578
Cosman F, Hattersley G, Hu MY, Williams GC, Fitzpatrick LA, Black DM (2017) Effects of abaloparatide-SC on fractures and bone mineral density in subgroups of postmenopausal women with osteoporosis and varying baseline risk factors. J Bone Miner Res 32(1):17–23
Gielen E, Bergmann P, Bruyère O, Cavalier E, Delanaye P, Goemaere S, Kaufman JM, Locquet M, Reginster JY, Rozenberg S, Vandenbroucke AM, Body JJ (2017) Osteoporosis in frail patients: a consensus paper of the Belgian Bone Club. Calcif Tissue Int 101(2):111–131
Kanis JA, Rizzoli R, Cooper C, Reginster JY (2014) Challenges for the development of bone-forming agents in Europe. Calcif Tissue Int 94(5):469–473
Ralston SH, Rizzoli R (2016) New targets and new treatments: recent advances in the treatment of musculoskeletal disease. Calcif Tissue Int 98(4):317–318
Cosman F, Miller PD, Williams GC, Hattersley G, Hu MY, Valter I, Fitzpatrick LA, Riis BJ, Christiansen C, Bilezikian JP, Black D (2017) Eighteen months of treatment with subcutaneous abaloparatide followed by 6 months of treatment with alendronate in postmenopausal women with osteoporosis: results of the ACTIVExtend trial. Mayo Clin Proc 92(2):200–210
Bone HG, Cosman F, Miller PD, Williams GC, Hattersley G, Hu MY, Fitzpatrick LA, Mitlak B, Papapoulos S, Rizzoli R, Dore RK, Bilezikian JP, Saag KG (2018) ACTIVExtend: 24 months of alendronate after 18 months of abaloparatide or placebo for postmenopausal osteoporosis. J Clin Endocrinol Metab. 10.1210/jc.2018-00163
McCloskey EV, Johansson H, Oden A, Harvey NC, Jiang H, Modin S, Fitzpatrick L, Kanis JA (2017) The effect of abaloparatide-SC on fracture risk is independent of baseline FRAX fracture probability: a post hoc analysis of the ACTIVE study. J Bone Miner Res 32(8):1625–1631
Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344(19):1434–1441
Lewiecki EM, Miller PD, Harris ST, Bauer DC, Davison KS, Dian L, Hanley DA, McClung MR, Yuen CK, Kendler DL (2014) Understanding and communicating the benefits and risks of denosumab, raloxifene, and teriparatide for the treatment of osteoporosis. J Clin Densitom 17(4):490–495
