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Comparative Effectiveness and Safety of Biosimilar and Legacy Drugs

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ClinicalTrials.gov Identifier: NCT03729674
Recruitment Status : Not yet recruiting
First Posted : November 5, 2018
Last Update Posted : November 26, 2018
Sponsor:
Collaborators:
Université de Sherbrooke
Institut de rhumatologie de Montréal
Hospital for Special Surgery, New York
University of Manitoba
University of Toronto
University of Alberta
University of British Columbia
Alberta Health Services
McMaster University
The Arthritis Program Research Group
Information provided by (Responsible Party):
Dr. Sasha Bernatsky, McGill University Health Center

Brief Summary:

In Canada and worldwide there is a need for updated independent real-world comparative effectiveness and safety data related to biologic drugs including biosimilar drugs. Biosimilar drugs hold potential to improve access to needed therapies at reduced cost enabling savings to be reallocated to other needs. However updated real-world evidence on comparative effectiveness and safety of biosimilar drugs is lacking. Investigators aim to demonstrate feasibility of creating network of clinical cohorts and other resources to provide real-world information on use of biosimilar drugs in Canada.

The core revolves around clinical datasets but investigators will complement with other data sources. Investigators will review data from National Prescription Drug Utilization Information System database that contains prescription claims-level data collected from publicly financed drug benefit programs in different provinces to conduct an environmental scan of the use of biosimilars and respective legacy drugs and other anti-Tumor Necrosis Factor agents covered by provincial drug plans from 2014-2017. Initial analysis will help to confirm that use of biosimilars is lower than corresponding legacy drugs.

Biologic drugs are relatively new and expensive drugs; biosimilar medicines are similar to original biologic drugs but cost less. If patients receive biosimilar drugs rather than originator biologics healthcare systems may be able to save money. Those savings can be used for other health care needs to benefit more Canadians. However investigators do not have detailed information on safety and effectiveness of these biosimilar drugs. The aim of study is to compare safety and effectiveness of biosimilar drugs to originator biologic drugs. Investigators will study patients with inflammatory rheumatic diseases (RA and AS) and Inflammatory Bowel Disease (CD and UC) and across Canada on these drugs. Primary focus is on patients without history of biologic drug use but investigators will also study patients switching to biosimilar drug from an originator biologic drug. Investigators will measure how long patients stay on treatment, if patients require new treatment, if the patients' disease control improves and occurrence of side effects such as infection that could be related to these drugs.


Condition or disease Intervention/treatment
Rheumatoid Arthritis Ankylosing Spondylitis Ulcerative Colitis Crohn's Disease Drug: Biosimilar Drug: Originator (legacy) drug

  Show Detailed Description

Study Type : Observational [Patient Registry]
Estimated Enrollment : 800 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 54 Months
Official Title: Comparative Effectiveness and Safety of Biosimilar and Legacy Drugs
Estimated Study Start Date : November 26, 2018
Estimated Primary Completion Date : March 30, 2021
Estimated Study Completion Date : December 31, 2022


Group/Cohort Intervention/treatment
Biosimilar
Exposed group
Drug: Biosimilar
Biologic-naïve patients starting any biosimilar; patients switching to biosimilar from an alternative biologic therapy; or patients switching to a biosimilar after successfully completing and exiting a previous course of therapy with the equivalent originator drug.
Other Names:
  • Inflectra
  • Erelzi
  • Brenzys
  • All other anti-TNF biosimilars as they come to market

Originator (legacy) drug
Reference group
Drug: Originator (legacy) drug
Biologic-naïve patients starting any originator (legacy) drug; patients switching to an originator drug from an alternative biologic therapy; or patients starting a new cycle with the originator drug.
Other Names:
  • Remicade
  • Enbrel
  • All other originator anti-TNF agents




Primary Outcome Measures :
  1. Persistence on the initial treatment, measured as time in months to drug discontinuation. [ Time Frame: From cohort entry until the date of discontinuation of the initial therapy or date of death from any cause, whichever came first, assessed up to 54 months. ]
    In each of the four conditions (RA, AS, CD, UC), the primary outcome will be persistence on treatment, measured as time from the cohort entry, either the date of first biologic/biosimilar prescription (for biologic-naïve patients) or the date of switching to a biologic/biosimilar, until the date of discontinuation of the initial therapy or date of death from any cause, whichever came first.


Secondary Outcome Measures :
  1. Proportion of participants discontinuing/switching the initial treatment due to treatment failure or adverse events. [ Time Frame: Months 3, 6, 12, 18, 24, 36, 48, and 54 ]
    In each of the four conditions (RA, AS, CD, UC), discontinuation/switching due to treatment failure (primary or secondary) or adverse events will be defined by the physician-in-charge of treatment.

  2. Time in months from cohort entry to treatment discontinuation/switching due to treatment failure or adverse events. [ Time Frame: From cohort entry until the date of discontinuation/switching of treatment due to treatment failure or adverse events or date of death from any cause, whichever came first, assessed up to 54 months. ]
    In each of the four conditions (RA, AS, CD, UC), discontinuation/switching due to treatment failure (primary or secondary) or adverse events will be defined by the physician-in-charge of treatment.

  3. Proportion of participants who modified therapy during follow-up. [ Time Frame: Months 3, 6, 12, 18, 24, 36, 48, and 54 ]
    In each of the four conditions (RA, AS, CD, UC), modified therapy is defined as starting or increasing dose of corticosteroids (intramuscular, intravenous, or high dose oral corticosteroid), initiating or re-introducing a non-biologic DMARD drug, or initiating or re-introducing a second biologic DMARD, during the follow-up.

  4. In RA participants, change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score at months 12, 24, and 48. [ Time Frame: Months 12, 24, and 48 ]
    The HAQ-DI is a questionnaire specific for rheumatoid arthritis and consists of 20 questions referring to 8 domains: Dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Participants completed the questionnaire by answering the 20 questions on a scale of 0 (without difficulty) to 3 (unable to do). The total score ranges from 0 (no disability) to 3 (completely disabled). A negative change score indicates improvement.

  5. Change from baseline in the European Quality of Life-5 Dimensions (EQ-5D) score at months 12 and 24. [ Time Frame: Months 12, 24, and 48 ]
    The EQ-5D is a standardized and self-report instrument for health status, which is applicable to a wide range of health conditions and treatments. The change in EQ-5D will be measured in each of the four conditions (RA, AS, CD, UC).

  6. Proportion of RA participants achieving disease remission assessed using the Disease Activity Score 28 (DAS28). [ Time Frame: Months 3, 6, 12, 18, 24, 36, 48, and 54 ]
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and either the erythrocyte sedimentation rate (DAS28-ESR) or C-reactive protein (DAS28-CRP). DAS28 remission is defined as a DAS28-ESR score < 2.6 or DAS28-CRP score < 2.4.

  7. Proportion of RA participants achieving sustained disease remission assessed using the DAS28. [ Time Frame: Months 12, 18, 24, 36, 48, and 54 ]
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and either the erythrocyte sedimentation rate (DAS28-ESR) or C-reactive protein (DAS28-CRP). Sustained remission is defined as a DAS28-ESR score < 2.6 or DAS28-CRP score < 2.4 for a minimum of 12 months.

  8. Proportion of RA participants achieving low disease activity (LDA) assessed using DAS28. [ Time Frame: Months 3, 6, 12, 18, 24, 36, 48, and 54 ]
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and either the erythrocyte sedimentation rate (DAS28-ESR) or C-reactive protein (DAS28-CRP). LDA is defined as a DAS28-ESR score ≤ 3.2 or DAS28-CRP score ≤ 2.9.

  9. Proportion of AS participants achieving an ASAS20 response [ Time Frame: Months 3, 6, 12, 18, 24, 36, 48, and 54 ]
    ASAS Response Criteria (ASAS 20): improvement of at least 20% in three of the four ASAS domain in comparison with the previous measurement.

  10. Proportion of AS participants achieving sustained remission using the Ankylosing Spondylitis Disease Activity Score (ASDAS) [ Time Frame: Months 12, 18, 24, 36, 48, and 54 ]

    The ASDAS score is calculated as the sum of the following components:

    0.121 × Back pain (BASDAI Question (Q)2 result) 0.058 × Duration of morning stiffness (BASDAI Q6 result) 0.110 × PtGADA, 0.073 × Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm of the CRP [mg/L] + 1) Spinal pain, PtGADA, duration of morning stiffness, peripheral pain/swelling and fatigue are all assessed on a numerical scale (0 to 10 units). The results of these calculations are summed to calculate the ASDAS. Sustained remission is defined as ASDAS < 1.3 for a minimum of 12 months


  11. Proportion of UC participants with induction of response within 3 months of initiation of treatment using the partial Mayo Score (PMS) [ Time Frame: Month 3 ]
    The PMS is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Induction of response is defined as a reduction in the PMS of at least 3 points and/or 30% from baseline with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1.

  12. Proportion of UC participants with sustained response after initiation of treatment using the PMS. [ Time Frame: Months 6, 12, 18, 24, 36, 48, and 54 ]
    The PMS is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Sustained response is defined as a maintenance of reduction in the PMS of at least 3 points and/or 30% from baseline with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1 in two consecutive visits.

  13. Proportion of UC participants achieving clinical remission using the PMS. [ Time Frame: Months 3, 6, 12, 18, 24, 36, 48, and 54 ]
    The PMS is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Clinical remission is defined as PMS ≤2, with no sub score >1.

  14. Proportion of UC participants with sustained clinical remission using the PMS. [ Time Frame: Months 6, 12, 18, 24, 36, 48, and 54 ]
    The PMS is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Sustained clinical remission is defined as PMS ≤2, with no sub score >1 in two consecutive visits.

  15. Proportion of UC participants with of loss of clinical response among responders using the PMS. [ Time Frame: Months 6, 12, 18, 24, 36, 48, and 54 ]
    The PMS is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Loss of clinical response is defined as a failure to maintain response in responder patients.

  16. Proportion of CD participants with induction of response within 3 months of initiation of treatment using the Harvey-Bradshaw Index (HBI) [ Time Frame: Month 3 ]
    The HBI is a 5-item scale that assesses general well-being, abdominal pain, diarrhea, abdominal mass, and complications. Induction of response is defined as a reduction in the HBI score of at least three points at 3 months after treatment initiation.

  17. Proportion of CD participants with sustained response after initiation of treatment using the HBI. [ Time Frame: Months 6, 12, 18, 24, 36, 48, and 54 ]
    The HBI is a 5-item scale that assesses general well-being, abdominal pain, diarrhea, abdominal mass, and complications. Sustained response is defined as a maintenance of reduction in the HBI of at least three points in two consecutive visits.

  18. Proportion of CD participants achieving clinical remission using the HBI. [ Time Frame: Months 3, 6, 12, 18, 24, 36, 48, and 54 ]
    The HBI is a 5-item scale that assesses general well-being, abdominal pain, diarrhea, abdominal mass, and complications. Clinical remission is defined as HBI ≤4.

  19. Proportion of CD participants with sustained clinical remission using the HBI. [ Time Frame: Months 6, 12, 18, 24, 36, 48, and 54 ]
    The HBI is a 5-item scale that assesses general well-being, abdominal pain, diarrhea, abdominal mass, and complications. Sustained clinical remission is defined as HBI ≤4 in two consecutive visits.

  20. Proportion of CD participants with of loss of clinical response among responders using the HBI. [ Time Frame: Months 6, 12, 18, 24, 36, 48, and 54 ]
    The HBI is a 5-item scale that assesses general well-being, abdominal pain, diarrhea, abdominal mass, and complications. Loss of clinical response is defined as a failure to maintain response (HBI ≤4) in responder patients.

  21. Change from baseline in the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) score at months 12, 24, and 48 in UC and CD participants. [ Time Frame: Months 12, 24, and 48. ]
    The SIBDQ is a Health-related quality of life (HRQOL) assessment tool for patients with IBD. The SIBDQ utilizes 10 items concerning patient well-being during the last 2 weeks, each of which is scored on a scale of 1 (poor HRQOL) to 7 (optimum HRQOL). SIBDQ scores range from 10 to 70 with higher values indicating better HRQOL. Positive changes indicate reductions in disease activity.


Other Outcome Measures:
  1. Proportion of participants with Adverse Events (AEs), serious AEs (SAEs), and deaths. [ Time Frame: From cohort entry until the end of study (54 months) ]
    Adverse events (AEs) will be assessed by the treating physician, who will judge the relationship between the study drug and the AE. SAEs (our primary outcome for safety) will be defined as an AE that is fatal or life-threatening, requiring or extending a patient's hospitalization, resulting in persistent or significant disability or incapacity, inducing a congenital anomaly or birth defect, or otherwise be considered important medical event by the physician. All deaths will be reported whether they were treatment-related or not. Adverse events of special interest for this study include infection (tuberculosis, fungal and other opportunistic infections, hepatitis B reactivation, and infections requiring hospitalization, an emergency room visit, or intravenous antibiotics) serious infusion reactions, cytopenias (i.e. leukopenia, drug-related anemia), new-onset congestive heart failure, malignancies, and demyelinating disorders.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Investigators will be working with two types of cohorts; more specifically, new cohorts collecting data prospectively and established cohorts that will share retrospective and prospective data as per Data Transfer Agreements. Data from these cohorts will be analyzed together.

Enrolment

Investigators are working with pan-Canadian, prospective cohorts of patients with inflammatory rheumatic diseases (rheumatoid arthritis, RA, and ankylosing spondylitis, AS) and Inflammatory Bowel Disease (IBD) (Crohn's disease, CD, and Ulcerative Colitis, UC). Cohort members eligible for the study are patients starting treatment with any biosimilar or any legacy drug. Patients will be enrolled over an approximate 24 month-period and the follow-up period will be up to four and a half years.

Criteria

Inclusion Criteria:

The study will include cohort members from both sexes, 18 years and older, with a clinical diagnosis of inflammatory rheumatic disease (either RA or AS), or IBD (CD or UC) who have given their informed consent. There are no disease activity criteria for entry. At the time of enrolment, patients in each disease group will be classified into the following treatment subgroups:

  • Biologic-naïve, starting any biosimilar or the equivalent legacy drug;
  • Patients switching to biosimilar or the equivalent legacy drug from an alternative biologic therapy;
  • Patients switching to a biosimilar (or starting a new cycle with the equivalent legacy drug), successfully completed and exited a previous course of therapy with the equivalent legacy drug.

Exclusion Criteria:

  • Under 18 years of age
  • No clinical diagnosis of inflammatory rheumatic disease (either RA or AS), or IBD (CD or UC)
  • Refused to participate or sign informed consent

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 ClinicalTrials.gov identifier (NCT number): NCT03729674


Contacts
Contact: Cristiano Moura, PhD 514-934-1934 ext 44714 cristiano.soaresdemoura@mail.mcgill.ca
Contact: Autumn Neville, MSc 514-934-1934 ext 44844 autumn.neville@rimuch.ca

Sponsors and Collaborators
McGill University Health Center
Université de Sherbrooke
Institut de rhumatologie de Montréal
Hospital for Special Surgery, New York
University of Manitoba
University of Toronto
University of Alberta
University of British Columbia
Alberta Health Services
McMaster University
The Arthritis Program Research Group

Additional Information:
Publications:
Responsible Party: Dr. Sasha Bernatsky, Principal Investigator, McGill University Health Center
ClinicalTrials.gov Identifier: NCT03729674     History of Changes
Other Study ID Numbers: MP-37-2019-4560
First Posted: November 5, 2018    Key Record Dates
Last Update Posted: November 26, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Dr. Sasha Bernatsky, McGill University Health Center:
Inflammatory rheumatic diseases Inflammatory Bowel Diseases

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Crohn Disease
Colitis, Ulcerative
Spondylitis
Spondylitis, Ankylosing
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Colitis
Colonic Diseases
Bone Diseases, Infectious
Infection
Bone Diseases
Spinal Diseases
Spondylarthropathies
Spondylarthritis
Ankylosis