Teriparatide for Joint Erosions in Rheumatoid Arthritis: The TERA Trial

NCT01400516 | Completed Phase 4 Results DMC

• 1 other identifier: 2010P002691
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief Summary

Summary: The investigators propose a randomized controlled open label study of teriparatide in men or women with rheumatoid arthritis and joint erosions. Specifically, the investigators will examine whether teriparatide in combination with a biologic can retard the development of joint erosions. The study will be conducted at Brigham and Women's Hospital Arthritis Center, several Brigham and Women's Hospital Arthritis Center satellite practices, the University of Massachusetts Medical Center, and Massachusetts General Hospital. Hypothesis: The investigators hypothesize that the combination of teriparatide with biologic will be much more effective at retarding erosion progression then a biologic alone.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Bone erosion; Osteopenia

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Joint Erosion Volume Measured by 3-Dimensional Computed Tomography (3D CT) Scan

  Both hands were scanned using a CT scanner. A semi-automated software tool was used to segment the erosion margins in 3D. A board certified radiologist identified the individual erosions in six sub-regions: radius, ulna, proximal carpals, distal carpals, metacarpophalangeal (MCP) joints and proximal interphalangeal (PIP) joints. The average total in a single hand/wrist was calculated. A negative change from Baseline(less joint erosions) indicates improvement.

  Baseline and Month 12

Secondary Outcomes (2)

• Change From Baseline in Bone Mineral Density (BMD) Measured by Dual-Energy X-ray Absorptiometry (DXA) and Instant Vertebral Assessment (IVA) Scan

  Baseline and Month 12

• Change From Baseline in Disease Activity Score 28 Joint Count C-Reactive Protein (DAS-28 CRP)

  Baseline and Month 12

Study Arms (2)

Teriparatide

EXPERIMENTAL

The participants who are in treatment arm received teriparatide 20 μg, subcutaneous injection, 1 injection per day, with a biologic for 12 months. A second year of teriparatide was offered to all interested participants. All participants received daily 1000 milligrams (mg) of calcium citrate, 800 IU of vitamin D and a Tumor Necrosis Factor (TNF) antagonist.

Drug: Teriparatide; Drug: calcium citrate; Drug: Vitamin D; Drug: TNF antagonist

Control Arm

OTHER

The participants randomized to the control arm had the same testing as those in the treatment arm and were offered teriparatide, if determined to be effective in healing bone erosions, after the first 12 months. All participants received daily 1000 mg of calcium citrate, 800 IU of vitamin D and a TNF antagonist.

Drug: calcium citrate; Drug: Vitamin D; Drug: TNF antagonist

Interventions

Teriparatide DRUG

20 μg, subcutaneous injection, 1 injection per day

Also known as: Forteo

Teriparatide

calcium citrate DRUG

1000 mg of calcium citrate

Control Arm; Teriparatide

Vitamin D DRUG

800 IU of Vitamin D

Control Arm; Teriparatide

TNF antagonist DRUG

TNF antagonist as prescribed in clinical practice (such as etanercept or adalimumab)

Control Arm; Teriparatide

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All men and women 45 years of age or older with RA and joint erosions by plain x-ray who are taking a biologic for at least three months and who have not taken more than two weeks of a bone active agent in the last 12 months will be eligible and screened for their interest in participating in the proposed randomized trial.
• RA will be defined according to the 2010 American College of Rheumatology/European League Against Rheumatism diagnostic and classification criteria.
• Osteopenic bone mineral density will be defined as a t-score between -1.0 and -2.5 on either a DXA of the posteroanterior (PA) or lateral lumbar spine or the femoral neck or total hip. Potential subjects with prior minimal trauma fractures will be excluded.
• Subjects must be able to give written informed consent.

You may not qualify if:

• A switch in DMARD in the last 3 months;
• Current use of chronic oral glucocorticoids \> 5 milligrams per day;
• A prior history of intolerance to teriparatide;
• T-score \< -2.5 or a prior minimal trauma fracture;
• Use of a bone active agent for over 2 weeks in the last 12 months (these agents include oral and intravenous bisphosphonates, hormone replacement therapy, calcitonin, raloxifene, teriparatide, suppressive doses of thyroxine, lithium, pharmacological doses of vitamin D (greater than 2000 IU/day or anticonvulsants);
• History of significant cardiac, hepatic, current alcohol abuse, or major psychiatric disorders;
• Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including hematologic malignancies and solid tumors, except basal cell carcinoma of the skin that has been excised and cured), or breast cancer diagnosed within the previous 20 years;
• No current diagnoses of disorders known to affect bone metabolism including hyperthyroidism, hyperparathyroidism, osteomalacia, or Paget's disease. All participants will be required to have normal serum levels of 25-OH vitamin D (\> 20 ng/ml), intact PTH, and thyroid stimulating hormone (TSH). If PTH and/or 25-hydroxy vitamin D (25-OH D) levels are abnormal, subjects may be given calcium and/or multivitamin supplements and be re-tested in 2-12 weeks;
• Serum calcium (Ca) \> 10.6 mg/dl,and 24-hour urine calcium \> 400 mg. If minor abnormalities are detected in any of these parameters, the test may be repeated;
• Patients who have had external beam radiation; and
• Patients currently on digoxin.
• Women that are currently pregnant or breast-feeding or plan on becoming pregnant over the course of participation in the study

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Eli Lilly and Company: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01605, United States

Location

Related Publications (13)

• Rasch EK, Hirsch R, Paulose-Ram R, Hochberg MC. Prevalence of rheumatoid arthritis in persons 60 years of age and older in the United States: effect of different methods of case classification. Arthritis Rheum. 2003 Apr;48(4):917-26. doi: 10.1002/art.10897.

  PMID: 12687533 BACKGROUND

• Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK. Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register. Arthritis Rheum. 2000 Mar;43(3):522-30. doi: 10.1002/1529-0131(200003)43:33.0.CO;2-Y.

  PMID: 10728744 BACKGROUND

• Hooyman JR, Melton LJ 3rd, Nelson AM, O'Fallon WM, Riggs BL. Fractures after rheumatoid arthritis. A population-based study. Arthritis Rheum. 1984 Dec;27(12):1353-61. doi: 10.1002/art.1780271205.

  PMID: 6508860 BACKGROUND

• Michel BA, Bloch DA, Wolfe F, Fries JF. Fractures in rheumatoid arthritis: an evaluation of associated risk factors. J Rheumatol. 1993 Oct;20(10):1666-9.

  PMID: 8295176 BACKGROUND

• Spector TD, Hall GM, McCloskey EV, Kanis JA. Risk of vertebral fracture in women with rheumatoid arthritis. BMJ. 1993 Feb 27;306(6877):558. doi: 10.1136/bmj.306.6877.558. No abstract available.

  PMID: 8461772 BACKGROUND

• Hall GM, Spector TD, Griffin AJ, Jawad AS, Hall ML, Doyle DV. The effect of rheumatoid arthritis and steroid therapy on bone density in postmenopausal women. Arthritis Rheum. 1993 Nov;36(11):1510-6. doi: 10.1002/art.1780361105.

  PMID: 8240428 BACKGROUND

• Cooper C, Coupland C, Mitchell M. Rheumatoid arthritis, corticosteroid therapy and hip fracture. Ann Rheum Dis. 1995 Jan;54(1):49-52. doi: 10.1136/ard.54.1.49.

  PMID: 7880122 BACKGROUND

• Saag KG, Emkey R, Schnitzer TJ, Brown JP, Hawkins F, Goemaere S, Thamsborg G, Liberman UA, Delmas PD, Malice MP, Czachur M, Daifotis AG. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med. 1998 Jul 30;339(5):292-9. doi: 10.1056/NEJM199807303390502.

  PMID: 9682041 BACKGROUND

• Cohen S, Levy RM, Keller M, Boling E, Emkey RD, Greenwald M, Zizic TM, Wallach S, Sewell KL, Lukert BP, Axelrod DW, Chines AA. Risedronate therapy prevents corticosteroid-induced bone loss: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 1999 Nov;42(11):2309-18. doi: 10.1002/1529-0131(199911)42:113.0.CO;2-K.

  PMID: 10555025 BACKGROUND

• Adachi JD, Bensen WG, Brown J, Hanley D, Hodsman A, Josse R, Kendler DL, Lentle B, Olszynski W, Ste-Marie LG, Tenenhouse A, Chines AA. Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med. 1997 Aug 7;337(6):382-7. doi: 10.1056/NEJM199708073370603.

  PMID: 9241127 BACKGROUND

• Lane NE, Sanchez S, Modin GW, Genant HK, Pierini E, Arnaud CD. Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial. J Clin Invest. 1998 Oct 15;102(8):1627-33. doi: 10.1172/JCI3914.

  PMID: 9788977 BACKGROUND

• Eggelmeijer F, Papapoulos SE, van Paassen HC, Dijkmans BA, Valkema R, Westedt ML, Landman JO, Pauwels EK, Breedveld FC. Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three-year randomized, double-blind trial. Arthritis Rheum. 1996 Mar;39(3):396-402. doi: 10.1002/art.1780390307.

  PMID: 8607888 BACKGROUND

• Solomon DH, Kay J, Duryea J, Lu B, Bolster MB, Yood RA, Han R, Ball S, Coleman C, Lo E, Wohlfahrt A, Sury M, Yin M, Yu Z, Zak A, Gravallese EM. Effects of Teriparatide on Joint Erosions in Rheumatoid Arthritis: A Randomized Controlled Trial. Arthritis Rheumatol. 2017 Sep;69(9):1741-1750. doi: 10.1002/art.40156. Epub 2017 Jul 14.

  PMID: 28544807 DERIVED

Related Links

• Brigham and Women's Clinical Trials

MeSH Terms

Conditions

Arthritis, Rheumatoid; Bone Diseases, Metabolic

Interventions

Teriparatide; Calcium Citrate; Vitamin D; Tumor Necrosis Factor Inhibitors

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Bone Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Parathyroid Hormone; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Calcium Compounds; Inorganic Chemicals; Citric Acid; Citrates; Tricarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Anti-Inflammatory Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Daniel H Solomon, MD, MPH
• Organization: Brigham and Women's Hospital

dsolomon@partners.org

Study Officials

• Daniel H Solomon, MD, MPH

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Ellen M. Gravallese, MD

  University of Massachusetts, Worcester

  PRINCIPAL INVESTIGATOR

• Jonathan Kay, MD

  University of Massachusetts, Worcester

  PRINCIPAL INVESTIGATOR

• Marcy B. Bolster, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 21, 2011
• First Posted: July 22, 2011
• Study Start: August 1, 2011
• Primary Completion: July 30, 2015
• Study Completion: July 28, 2016
• Last Updated: April 11, 2017
• Results First Posted: April 11, 2017

Record last verified: 2017-02

Locations

US (3)