Cimzia Treatment in Rheumatoid Arthritis: Randomizing to Stop Versus Continue Disease-modifying Anti-rheumatic Drug(s)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01489384
Recruitment Status : Active, not recruiting
First Posted : December 9, 2011
Last Update Posted : April 13, 2017
Information provided by (Responsible Party):
Pope Research Corporation

Brief Summary:

The purpose of this study is to investigate the safety and efficacy of Cimzia given as an add-on to your current therapy with disease-modifying anti-rheumatic drug(s) (DMARDs)including MTX or given as monotherapy (alone) over an 18 month period.

Approximately 125 patients with moderate to severe Rheumatoid Arthritis (RA) who are being prescribed Cimzia will be enrolled into the study.

Condition or disease
Rheumatoid Arthritis

Detailed Description:

Rheumatoid arthritis is a chronic systemic inflammatory disease that is associated with significant morbidity and mortality. The disease is characterized by inflammation of synovial joints that can result in pain, swelling and joint damage with secondary deformity and progressive disability and impairment of patient's health related quality of life. It is estimated that about 1% of the population worldwide has RA.

Treatment for RA includes use of nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) selective inhibitors, corticosteroids and DMARDs. The effectiveness and toxicities associated with use of DMARDs differs based on the individual agent; DMARDs are often partially effective. For those in whom DMARDs have not fully treated RA, TNF inhibitors are often prescribed.

TNFα plays an important role in RA. Activities ascribed to TNFα in RA include recruitment and activation of polymorphonuclear leukocytes (PMNs), cellular proliferation, increased prostaglandin and matrix-degrading protease activity, and bone and cartilage resorption.

CIMZIA (certolizumab pegol) in combination with methotrexate (MTX) is indicated for:

• reducing signs and symptoms, inducing major clinical response, and reducing the progression of joint damage as assessed by X-ray, in adult patients with moderately to severely active rheumatoid arthritis (RA).

Study Type : Observational
Actual Enrollment : 125 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Canadian Randomized Controlled Trial of DMARD Withdrawal in RA Patients Achieving Therapeutic Response With Cimzia + DMARD Combination Treatment.
Study Start Date : December 2011
Estimated Primary Completion Date : August 27, 2018
Estimated Study Completion Date : September 2018

Resource links provided by the National Library of Medicine

3 months: Discontinue vs continue DMARDS
At 3 months those patients who achieved a change in DAS28 of 1.2 or greater will be randomized to discontinue versus continue DMARDs and will be followed for an additional 15 months
6 months: discontinue vs continue DMARDs
(Protocol amendment 4.0)At 6 months, those patients still on Cimzia and DMARD therapy who were not randomized at month 3 AND achieve a change in DAS28> 1.2 will be randomized to discontinue versus continue DMARDs and will be followed for an additional 12 months.
6 months: D/C vs Cont'd DMARDs if change in DAS28
(Protocol amendment 4.0)At 6 months, if the change in DAS28 is at least 0.6 and there is a decision to continue Cimzia, then the patients will be randomized to discontinue versus continue DMARDs with Cimzia and will be followed for an additional 12 months.
3 or 6 months: stop CIMZIA and treat as per SOC
(Protocol amendment 4.0)If a change in DAS28 of <0.6 occurs at 6 months (at 3 months for protocol amendment 6.1)in patients not randomized at month 3 then the patient will stop Cimzia and treatment will be standard of care. However, patient will still be followed until the end of study.

Primary Outcome Measures :
  1. The percentage of patients achieving DAS28<3.2 or maintaining a change in DAS from baseline of ≥ 1.2 at 18 months. [ Time Frame: At 18 months ]
    Between-group differences with respect to the proportion of subjects achieving DAS28<3.2 will be assessed for statistical significance with the Chi-square test. Multiple-logistic regression model with terms for treatment group and potential confounders will be used to produce adjusted estimates of the relative rate of achieving therapeutic effectiveness. Time to achieving DAS28<3.2 will be assessed with Kaplan Meier survival analysis.

Secondary Outcome Measures :
  1. Mean change from baseline in DAS28 score in each group at 18 months [ Time Frame: At 18 months ]
    Between-group differences will be assessed for statistical significance with One Way ANOVA. General Linear Models will be used to adjust the between-group differences for potential confounders identified during the assessment of the baseline and demographic characteristics.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients who had not had an adequate response to a DMARD therapy will have Cimzia added to their existing DMARD therapy at baseline and will be followed.

Inclusion Criteria:

  1. Patient must be ≥ 18 years of age.
  2. Patient must be able to understand the information provided to them and to give written Informed Consent.
  3. Patient must fulfill the old or new criteria for RA (see Appendix 1) or have a clinical diagnosis of RA.
  4. Patient must be receiving (for 3 months before baseline) one of the following: methotrexate (≥ 12.5 mg) or another DMARD (leflunomide 10 to 20 mg/day, sulfasalazine >1000 mg/day, IM myochrysine for at least 20 weeks at 25 mg per month or more, azathioprine> 75mg/day), or combination DMARDs such as methotrexate with any other DMARD, or other combinations.
  5. If patient is on prednisone they must be on a stable dose (≤ 10 mg/day) for 1 month prior to baseline.
  6. Patient with active RA (≥ 3 SJC, on 28 joint count) who needs anti-TNF therapy as determined by the investigator and ability to obtain coverage for anti-TNF (Cimzia).
  7. Patient must not have previously been exposed to Cimzia, however, previous anti-TNF exposure is allowed.
  8. Patient with past anti-TNF exposure will be included if 1st anti-TNF was stopped due to secondary loss of efficacy, side effect or discontinuation for other reasons.
  9. Patient must use Cimzia as per the dosing guidelines in the approved product monograph.

Exclusion Criteria:

  1. Female patient who is breast-feeding or pregnant or does plan to become pregnant over the next year
  2. Failure to use acceptable form of contraception in a pre-menopausal woman
  3. Patient with concurrent serious liver disease
  4. Patient with concurrent serious renal disease
  5. Patient with significant hematological impairments
  6. Patient with a history of cancer within the last 2 years, other than a successfully treated skin basal cell or squamous cell carcinoma and/or localized carcinoma in situ of the cervix
  7. Patient with a history of malignant lymphoma of leukemia
  8. Patient with a history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease (e.g. Multiple Sclerosis)
  9. Patient with a history of untreated active tuberculosis
  10. Patient with positive PPD (>5 mm) who have not had prophylaxis
  11. Patient with a known positive HIV test
  12. Patient with a persistent or severe infection(s) requiring hospitalization or treatment with iv antibiotics within 30 days or oral antibiotics within 7 days prior to baseline.
  13. Patient with significant congestive heart failure
  14. Patient with clinically significant concurrent medical of psychiatric disorders that in the physician's judgment may influence the study outcomes.
  15. Patient with any condition that would prevent participation or completion in this study including language limitation or possibility that the patient will not be available for the complete study period
  16. Patient with severe noncompliance
  17. Patient receiving an experimental product within the last 6 weeks prior to first dose of Cimzia.
  18. Other joint disease or joint pain condition where the patient or physician cannot distinguish RA assessments from the other joint disease
  19. Concomitant SLE
  20. Chest x-ray shows evidence of TB.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01489384

Canada, New Brunswick
Rhumatologie Moncton
Moncton, New Brunswick, Canada, E1G 2K5
Eric N. Grant Professional Corp.
Quispamsis, New Brunswick, Canada, E2E 4J8
Canada, Ontario
Bowmanville, Ontario, Canada, L1C 1P6
Dr.'s Nalin and Vandana Ahluwalia Medicine Professional Corp.
Brampton, Ontario, Canada, L6T 3J1
Brockville Medical Centre
Brockville, Ontario, Canada, K6V 5J9
The Arthritis Center
Burlington, Ontario, Canada, L7L 0B7
St. Joseph's Health Care
Guelph, Ontario, Canada, N1H 5H8
St-Joseph Health Center
London, Ontario, Canada, N6A 4V2
N.R. Medical Clinic
Markham, Ontario, Canada, L6E 0H7
Arthur Karasik Medicine Professional Corporation
Toronto, Ontario, Canada, M9C 5N2
Canada, Quebec
Institut de Rhumatologie de Montréal
Montreal, Quebec, Canada, H2L 1S6
G.R.M.O. (Groupe de recherche en maladies oseuses) Inc.
Quebec, Canada, G1V 3M7
Centre de Rhumatologie St-Louis
Quebec, Canada, G1W 4R4
Sponsors and Collaborators
Pope Research Corporation
Principal Investigator: Janet Pope, MD Pope Research Corporation

Responsible Party: Pope Research Corporation Identifier: NCT01489384     History of Changes
Other Study ID Numbers: PRC-06-2011
JSS-01-2013 ( Other Identifier: UCB Canada )
First Posted: December 9, 2011    Key Record Dates
Last Update Posted: April 13, 2017
Last Verified: April 2017

Keywords provided by Pope Research Corporation:
Rheumatoid arthritis

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antirheumatic Agents
Certolizumab Pegol
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs