Top

Osteoporosis International

Published in:

01-11-2020 | Tocilizumab | Original Article

Comparative risk of osteoporotic fracture among patients with rheumatoid arthritis receiving TNF inhibitors versus other biologics: a cohort study

Authors: A. Shin, E.H. Park, Y.-H. Dong, Y.-J. Ha, Y.J. Lee, E.B. Lee, Y.W. Song, E.H. Kang

Published in: Osteoporosis International | Issue 11/2020

Abstract

Summary

In this population-based cohort study on comparative osteoporotic fracture risks between different biologic disease-modifying drugs among patients with rheumatoid arthritis (RA), we did not find a significant difference in the risk of osteoporotic fractures between RA patients receiving TNF inhibitors versus abatacept or tocilizumab.

Introduction

We aimed to investigate the comparative risk of osteoporotic fractures between rheumatoid arthritis (RA) patients who initiated TNF inhibitors (TNFis) versus abatacept or tocilizumab.

Methods

Using the Korea National Health Insurance Service datasets from 2002 to 2016, RA patients who initiated TNFis, abatacept, or tocilizumab were identified. The primary outcome was a composite end point of non-vertebral fractures and hospitalized vertebral fractures; secondary outcomes were two components of the primary outcome and fractures occurring at the humerus/forearm. Propensity score (PS) matching with a variable ratio up to 10 TNFi initiators per 1 comparator drug initiator was used to adjust for > 50 baseline confounders. We estimated hazard ratios (HRs) and 95% confidence interval (CI) of fractures comparing TNFi initiators to abatacept and to tocilizumab by Cox proportional hazard models stratified by a matching ratio.

Results

After PS-matching, 2307 TNFi initiators PS-matched on 588 abatacept initiators, and 2462 TNFi initiators on 640 tocilizumab initiators were included. A total of 77 fractures occurred during a mean follow-up of 454 days among TNFi and abatacept initiators and 83 fractures during 461 days among TNFi and tocilizumab initiators. The PS-matched HR (95% CI) was 0.91 (0.48–1.71) comparing TNFi versus abatacept initiators, and 1.00 (0.55–1.83) comparing TNFi versus tocilizumab initiators. Analysis on vertebral and non-vertebral fractures showed similar results.

Conclusions

In this nationally representative cohort, we did not find a significant difference in the risk of fractures between TNFi initiators versus abatacept or tocilizumab among RA patients.

Available only for authorised users

McInnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365(23):2205–2219. https://doi.org/10.1056/NEJMra1004965CrossRefPubMed

Kleyer A, Schett G (2014) Arthritis and bone loss: a hen and egg story. Curr Opin Rheumatol 26(1):80–84. https://doi.org/10.1097/BOR.0000000000000007CrossRefPubMed

Kim SY, Schneeweiss S, Liu J, Daniel GW, Chang CL, Garneau K, Solomon DH (2010) Risk of osteoporotic fracture in a large population-based cohort of patients with rheumatoid arthritis. Arthritis Res Ther 12(4):R154. https://doi.org/10.1186/ar3107CrossRefPubMedPubMedCentral

Desai RJ, Solomon DH, Jin Y, Liu J, Kim SC (2017) Temporal trends in use of biologic DMARDs for rheumatoid arthritis in the United States: a cohort study of publicly and privately insured patients. J Manag Care Spec Pharm 23(8):809–814. https://doi.org/10.18553/jmcp.2017.23.8.809CrossRefPubMed

Manara M, Sinigaglia L (2015) Bone and TNF in rheumatoid arthritis: clinical implications. RMD Open 1(Suppl 1):e000065. https://doi.org/10.1136/rmdopen-2015-000065CrossRefPubMedPubMedCentral

Ozen G, Pedro S, Wolfe F, Michaud K (2019) Medications associated with fracture risk in patients with rheumatoid arthritis. Ann Rheum Dis 78(8):1041–1047. https://doi.org/10.3390/jcm7120507CrossRefPubMed

Tada M, Inui K, Sugioka Y, Mamoto K, Okano T, Koike T (2018) Abatacept might increase bone mineral density at femoral neck for patients with rheumatoid arthritis in clinical practice: AIRTIGHT study. Rheumatol Int 38(5):777–784. https://doi.org/10.1007/s00296-017-3922-zCrossRefPubMed

Garnero P, Thompson E, Woodworth T, Smolen JS (2010) Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone. Arthritis Rheum 62(1):33–43. https://doi.org/10.1002/art.25053CrossRefPubMed

Kume K, Amano K, Yamada S, Kanazawa T, Ohta H, Hatta K, Amano K, Kuwaba N (2014) The effect of tocilizumab on bone mineral density in patients with methotrexate-resistant active rheumatoid arthritis. Rheumatology (Oxford) 53(5):900–903. https://doi.org/10.1093/rheumatology/ket468CrossRef

10.

Son JS, Choi S, Kim K, Kim SM, Choi D, Lee G, Jeong SM, Park SY, Kim YY, Yun JM, Park SM (2018) Association of Blood Pressure Classification in Korean young adults according to the 2017 American College of Cardiology/American Heart Association guidelines with subsequent cardiovascular disease events. JAMA 320(17):1783–1792. https://doi.org/10.1001/jama.2018.16501CrossRefPubMedPubMedCentral

11.

Kim SY, Servi A, Polinski JM, Mogun H, Weinblatt ME, Katz JN, Solomon DH (2011) Validation of rheumatoid arthritis diagnoses in health care utilization data. Arthritis Res Ther 13(1):R32. https://doi.org/10.1186/ar3260CrossRefPubMedPubMedCentral

12.

Cho SK, Sung YK, Choi CB, Kwon JM, Lee EK, Bae SC (2013) Development of an algorithm for identifying rheumatoid arthritis in the Korean National Health Insurance claims database. Rheumatol Int 33(12):2985–2992. https://doi.org/10.1007/s00296-013-2833-xCrossRefPubMed

13.

Fralick M, Kim SC, Schneeweiss S, Kim D, Redelmeier DA, Patorno E (2019) Fracture risk after initiation of use of Canagliflozin: a cohort study. Ann Intern Med 170:155–163. https://doi.org/10.7326/M18-0567CrossRefPubMedPubMedCentral

14.

Curtis JR, Mudano AS, Solomon DH, Xi J, Melton ME, Saag KG (2009) Identification and validation of vertebral compression fractures using administrative claims data. Med Care 47(1):69–72. https://doi.org/10.1097/MLR.0b013e3181808c05CrossRefPubMedPubMedCentral

15.

Ray WA, Griffin MR, Fought RL, Adams ML (1992) Identification of fractures from computerized Medicare files. J Clin Epidemiol 45(7):703–714CrossRefPubMed

16.

Hudson M, Avina-Zubieta A, Lacaille D, Bernatsky S, Lix L, Jean S (2013) The validity of administrative data to identify hip fractures is high--a systematic review. J Clin Epidemiol 66(3):278–285. https://doi.org/10.1016/j.jclinepi.2012.10.004CrossRefPubMed

17.

Schneider AL, Williams EK, Brancati FL, Blecker S, Coresh J, Selvin E (2013) Diabetes and risk of fracture-related hospitalization: the atherosclerosis risk in communities study. Diabetes Care 36(5):1153–1158. https://doi.org/10.2337/dc12-1168CrossRefPubMedPubMedCentral

18.

Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA (2004) New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol 57(12):1288–1294. https://doi.org/10.1016/j.jclinepi.2004.03.012CrossRefPubMed

19.

Pharmacoepidemiology Toolbox Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Havard Medical School. http://www.drugepi.org/dope-downloads/. Accessed 28 Aug 2019

20.

Kleinbaum DG (2012) Klein M survival analysis: a self, learning text, 3rd edn. Springer, New YorkCrossRef

21.

Smolen JS, Landewe R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, Nam J, Ramiro S, Voshaar M, van Vollenhoven R, Aletaha D, Aringer M, Boers M, Buckley CD, Buttgereit F, Bykerk V, Cardiel M, Combe B, Cutolo M, van Eijk-Hustings Y, Emery P, Finckh A, Gabay C, Gomez-Reino J, Gossec L, Gottenberg JE, Hazes JMW, Huizinga T, Jani M, Karateev D, Kouloumas M, Kvien T, Li Z, Mariette X, McInnes I, Mysler E, Nash P, Pavelka K, Poor G, Richez C, van Riel P, Rubbert-Roth A, Saag K, da Silva J, Stamm T, Takeuchi T, Westhovens R, de Wit M, van der Heijde D (2017) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 76(6):960–977. https://doi.org/10.1136/annrheumdis-2016-210715CrossRefPubMed

22.

Austin PC (2011) Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat 10(2):150–161. https://doi.org/10.1002/pst.433CrossRefPubMed

23.

Lee SH, Khang YH, Lim KH, Kim BJ, Koh JM, Kim GS, Kim H, Cho NH (2010) Clinical risk factors for osteoporotic fracture: a population-based prospective cohort study in Korea. J Bone Miner Res 25(2):369–378. https://doi.org/10.1359/jbmr.090722CrossRefPubMed

24.

Kawai VK, Grijalva CG, Arbogast PG, Curtis JR, Solomon DH, Delzell E, Chen L, Ouellet-Hellstrom R, Herrinton L, Liu L, Mitchell EF Jr, Stein CM, Griffin MR (2013) Initiation of tumor necrosis factor α antagonists and risk of fractures in patients with selected rheumatic and autoimmune diseases. Arthritis Care Res (Hoboken) 65(7):1085–1094. https://doi.org/10.1002/acr.21937CrossRef

25.

Okada H, Kajiya H, Omata Y, Matsumoto T, Sato Y, Kobayashi T, Nakamura S, Kaneko Y, Nakamura S, Koyama T, Sudo S, Shin M, Okamoto F, Watanabe H, Tachibana N, Hirose J, Saito T, Takai T, Matsumoto M, Nakamura M, Okabe K, Miyamoto T, Tanaka S (2019) CTLA4-Ig directly inhibits Osteoclastogenesis by interfering with intracellular calcium oscillations in bone marrow macrophages. J Bone Miner Res 34:1744–1752. https://doi.org/10.1002/jbmr.3754CrossRefPubMed

26.

Roser-Page S, Vikulina T, Zayzafoon M, Weitzmann MN (2014) CTLA-4Ig-induced T cell anergy promotes Wnt-10b production and bone formation in a mouse model. Arthritis Rheumatol 66(4):990–999. https://doi.org/10.1002/art.38319CrossRefPubMedPubMedCentral

27.

Bay-Jensen AC, Platt A, Byrjalsen I, Vergnoud P, Christiansen C, Karsdal MA (2014) Effect of tocilizumab combined with methotrexate on circulating biomarkers of synovium, cartilage, and bone in the LITHE study. Semin Arthritis Rheum 43(4):470–478. https://doi.org/10.1016/j.semarthrit.2013.07.008CrossRefPubMed

28.

Axmann R, Bohm C, Kronke G, Zwerina J, Smolen J, Schett G (2009) Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo. Arthritis Rheum 60(9):2747–2756. https://doi.org/10.1002/art.24781CrossRefPubMed

29.

Finzel S, Kraus S, Figueiredo CP, Regensburger A, Kocijan R, Rech J, Schett G (2019) Comparison of the effects of tocilizumab monotherapy and adalimumab in combination with methotrexate on bone erosion repair in rheumatoid arthritis. Ann Rheum Dis 78(9):1186–1191. https://doi.org/10.1136/annrheumdis-2018-214894CrossRefPubMed

30.

Briot K, Rouanet S, Schaeverbeke T, Etchepare F, Gaudin P, Perdriger A, Vray M, Steinberg G, Roux C (2015) The effect of tocilizumab on bone mineral density, serum levels of Dickkopf-1 and bone remodeling markers in patients with rheumatoid arthritis. Joint Bone Spine 82(2):109–115. https://doi.org/10.1016/j.jbspin.2014.10.015CrossRefPubMed

31.

Scheven BA, van der Veen MJ, Damen CA, Lafeber FP, Van Rijn HJ, Bijlsma JW, Duursma SA (1995) Effects of methotrexate on human osteoblasts in vitro: modulation by 1,25-dihydroxyvitamin D3. J Bone Miner Res 10(6):874–880. https://doi.org/10.1002/jbmr.5650100608CrossRefPubMed

32.

Prevoo ML, van't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38(1):44–48. https://doi.org/10.1002/art.1780380107CrossRefPubMed

33.

Raterman HG, Lems WF (2019) Pharmacological Management of Osteoporosis in rheumatoid arthritis patients: a review of the literature and practical guide. Drugs Aging 36(12):1061–1072. https://doi.org/10.1007/s40266-019-00714-4CrossRefPubMedPubMedCentral

34.

Yoshida K, Solomon DH, Kim SC (2015) Active-comparator design and new-user design in observational studies. Nat Rev Rheumatol 11(7):437–441. https://doi.org/10.1038/nrrheum.2015.30CrossRefPubMedPubMedCentral

35.

Hecht C, Englbrecht M, Rech J, Schmidt S, Araujo E, Engelke K, Finzel S, Schett G (2015) Additive effect of anti-citrullinated protein antibodies and rheumatoid factor on bone erosions in patients with RA. Ann Rheum Dis 74(12):2151–2156. https://doi.org/10.1136/annrheumdis-2014-205428CrossRefPubMed

Title: Comparative risk of osteoporotic fracture among patients with rheumatoid arthritis receiving TNF inhibitors versus other biologics: a cohort study
Authors: A. Shin
E.H. Park
Y.-H. Dong
Y.-J. Ha
Y.J. Lee
E.B. Lee
Y.W. Song
E.H. Kang
Publication date: 01-11-2020
Publisher: Springer London
Keywords: Tocilizumab
Abatacept
TNF-Inhibitors
Rheumatoid Arthritis
Published in: Osteoporosis International / Issue 11/2020
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-020-05488-9

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Comparative risk of osteoporotic fracture among patients with rheumatoid arthritis receiving TNF inhibitors versus other biologics: a cohort study

Abstract

Summary

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 11/2020

Persistent hyperparathyroidism due to mediastinal parathyroid adenoma treated with selective arterial embolization with embosphere: first case in the literature

Association of orthogeriatric care models with evaluation and treatment of osteoporosis: a systematic review and meta-analysis

FRAX and ethnicity

Multiple ipsilateral femoral stress fractures in a patient taking denosumab for osteoporosis—a case report

Persistence and adherence to parenteral osteoporosis therapies: a systematic review

An in-depth study of the associations between osteoarthritis- and osteoporosis-related phenotypes at different skeletal locations