A Pilot Study of the Feasibility of Discontinuation of Adalimumab in Stable Rheumatoid Arthritis Patients in Clinical Remission - Full Text View

Sponsors and Collaborators:	Abbott Pharma Consulting Group
Information provided by:	Abbott
ClinicalTrials.gov Identifier:	NCT00808509

Purpose

Rheumatoid arthritis is a chronic disease. Treatment with anti-rheumatic drugs, including TNF-blocking agents, are commonly used. Once started, these drugs are usually continued indefinitely. Information, concerning the possibility to discontinue anti-TNF therapy in RA patients who are in remission (i.e. no significant remaining disease activity) is limited.The purpose of this pilot study is to investigate if it is possible to stop therapy of adalimumab (a TNF-blocker) in patients with established RA in stable remission after treatment with adalimumab in combination with methotrexate.

Condition	Intervention	Phase
Arthritis, Rheumatoid	Biological: adalimumab Drug: methotrexate	Phase IV

MedlinePlus related topics: Rheumatoid Arthritis

Drug Information available for: Methotrexate Adalimumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Randomized, Open Label, Parallel Assignment

Further study details as provided by Abbott:

Primary Outcome Measures:

The proportions of RA patients in remission, defined as DAS28<2.6 at week 28, in arm 1 (adalimumab and MTX continued) and arm 2 (adalimumab discontinued, MTX continued). [ Time Frame: Week 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The proportions of RA patients in remission, defined as DAS28<2.6, at week 52 in arm 1 (adalimumab and MTX continued) and arm 2 (adalimumab discontinued, MTX continued). [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
The incidence of flare (defined as DAS28>2.6 or DAS28 increase >1.2 units) at week 4, 8, 12, 20, 28, 36, 44 and 52. [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
The response rate, defined as return to baseline DAS28+10% after reinstitution of adalimumab (after flare), evaluated at 4, 8 and 12 weeks [ Time Frame: Week 12 after adalimumab reinstitution. ] [ Designated as safety issue: No ]
The physical function, evaluated by HAQ at week 4, 8, 12, 20, 28, 36, 44 and 52. [ Time Frame: Week 52 ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	December 2008
Estimated Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Active comparator. Drug (adalimumab) continued.Study subjects are recruited from patients with rheumatoid arthritis who are in stable remission on adalimumab + methotrexate (MTX) (adalimumab + MTX prescribed in standard care prior to study entry) Continued treatment with adalimumab 40 mg eow plus Methotrexate (MTX; at least 10 mg/wk; orally or subcutaneously).	Biological: adalimumab 40 mg eow Drug: methotrexate at least 10 mg/wk; orally or subcutaneously
2: Experimental Study subjects are recruited from patients with rheumatoid arthritis who are in stable remission on adalimumab + methotrexate (MTX) (adalimumab + MTX prescribed in standard care prior to study entry) Discontinuation of adalimumab. MTX continued (at least 10 mg/wk; orally or subcutaneously).	Drug: methotrexate at least 10 mg/wk; orally or subcutaneously

Detailed Description:

Primary purpose (7a): Withdrawal of treatment: for details - see above.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age =/>18 years.
Diagnosis of RA as defined by the 1987-revised ACR-classification and has positive RF test or erosion on X-ray of hands or feet.
Subject is currently treated with adalimumab and MTX (at least 10 mg/week; orally or subcutaneously).
Subject is in remission as defined by DAS28<2.6 for at least the 3 past months.
Concomitant DMARD or oral corticosteroid therapy has been stable for at least 3 months at study entry.
Female subject is either not of childbearing potential or is practicing a relevant method of birth control (specified in the protocol).
Subject is judged to be in good general health.
Subjects must be able and willing to provide written informed consent.
Subjects must be able and willing to self-administer SC injections or have a qualified person available to administer SC injections.

Exclusion Criteria:

Treatment with intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks.
Oral prednisone or prednisone equivalent > 10 mg/day at baseline.
Joint surgery within the preceding two months.
History of acute inflammatory joint disease other than RA.
Treatment with any investigational drug within 30 days or 5 half lives - whichever is longer prior to study entry.
Poorly controlled medical condition, which would put the subject at risk by participation in the study.
History of clinically significant hematologic, renal or liver disease.
Diagnosis of, or history suggestive of, CNS demyelinating disease.
History of cancer or lymphoproliferative disease other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma of the cervix.
History of listeriosis, histoplasmosis, untreated TB, persistent chronic infections, or recent active infections.
Known immune deficiency or HIV.
Female subject who is pregnant or breast-feeding or considering becoming pregnant or breast feeding during the study.
History of clinically significant drug or alcohol usage in the last year.
Abnormal laboratory results at baseline:
AST or ALT >1.5x the upper limit.
Serum total bilirubin >1.5 mg/dL (>26µmol/L).
Creatinine >1.5 mg/dL (>133 µmol/L) in subjects < 65 years old and > upper limit of normal range in subjects >65.
Evidence of chronic Hepatitis B or C.
Subject is considered , for any reason, to be an unsuitable candidate for the study.
Prior exposure to Tysabri (natalizumab).
Known hypersensitivity to the excipients of adalimumab.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00808509

Contacts

Contact: Ewa Berndtson

+46 85 46 56 73 0

ewa.bendtson@abbott.com

Locations

Sweden

Stockholm, Sweden, 171 76

Huddinge, Sweden, 141 86

Uppsala, Sweden, 751 85

Oskarstrom, Sweden, 313 92

Eskilstuna, Sweden, 631 88

Lund, Sweden, 221 85

Malmo, Sweden, 205 20

Sponsors and Collaborators

Abbott

Pharma Consulting Group

Investigators

Study Director:

Mikael Heimburger, MD, PhD

Abbott (Abbott Scandinavia AB)

More Information

Responsible Party:	Abbott ( Abbott Scandinavia AB) ( Mikael Heimburger )
Study ID Numbers:	W10-046, EudraCT 2008-004398-16
Study First Received:	December 12, 2008
Last Updated:	December 12, 2008
ClinicalTrials.gov Identifier:	NCT00808509
Health Authority:	Sweden: Medical Products Agency

Keywords provided by Abbott:

Remission, adalimumab, drug discontinuation

Study placed in the following topic categories:

Folic Acid
Autoimmune Diseases
Musculoskeletal Diseases
Joint Diseases
Arthritis

Connective Tissue Diseases
Arthritis, Rheumatoid
Methotrexate
Rheumatic Diseases
Adalimumab

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Reproductive Control Agents

Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Pharmacologic Actions
Therapeutic Uses
Abortifacient Agents
Antirheumatic Agents
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 14, 2009