Rheumatoid Arthritis Clinical Trial
Official title:
Comparative Effectiveness and Safety of Biosimilar and Legacy Drugs
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.
Status | Recruiting |
Enrollment | 800 |
Est. completion date | December 31, 2022 |
Est. primary completion date | March 30, 2021 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
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 |
Country | Name | City | State |
---|---|---|---|
Canada | McGill University Health Centre at Montreal General Hospital | Montreal | Quebec |
Lead Sponsor | Collaborator |
---|---|
McGill University Health Centre/Research Institute of the McGill University Health Centre | Alberta Health Services, Hospital for Special Surgery, New York, Institut de rhumatologie de Montréal, McMaster University, The Arthritis Program Research Group, Université de Sherbrooke, University of Alberta, University of British Columbia, University of Manitoba, University of Toronto |
Canada,
Isakov L, Jin B, Jacobs IA. Statistical Primer on Biosimilar Clinical Development. Am J Ther. 2016 Nov/Dec;23(6):e1903-e1910. Review. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Proportion of participants with Adverse Events (AEs), serious AEs (SAEs), and deaths. | 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. | From cohort entry until the end of study (54 months) | |
Primary | Persistence on the initial treatment, measured as time in months to drug discontinuation. | 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. | 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. | |
Secondary | Proportion of participants discontinuing/switching the initial treatment due to treatment failure or adverse events. | 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. | Months 3, 6, 12, 18, 24, 36, 48, and 54 | |
Secondary | Time in months from cohort entry to treatment discontinuation/switching due to treatment failure or adverse events. | 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. | 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. | |
Secondary | Proportion of participants who modified therapy during follow-up. | 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. | Months 3, 6, 12, 18, 24, 36, 48, and 54 | |
Secondary | In RA participants, change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score at 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. | Months 12, 24, and 48 | |
Secondary | Change from baseline in the European Quality of Life-5 Dimensions (EQ-5D) score at months 12 and 24. | 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). | Months 12, 24, and 48 | |
Secondary | Proportion of RA participants achieving disease remission assessed using the Disease Activity Score 28 (DAS28). | 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. | Months 3, 6, 12, 18, 24, 36, 48, and 54 | |
Secondary | Proportion of RA participants achieving sustained disease remission assessed using the DAS28. | 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. | Months 12, 18, 24, 36, 48, and 54 | |
Secondary | Proportion of RA participants achieving low disease activity (LDA) assessed using DAS28. | 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. | Months 3, 6, 12, 18, 24, 36, 48, and 54 | |
Secondary | Proportion of AS participants achieving an ASAS20 response | ASAS Response Criteria (ASAS 20): improvement of at least 20% in three of the four ASAS domain in comparison with the previous measurement. | Months 3, 6, 12, 18, 24, 36, 48, and 54 | |
Secondary | Proportion of AS participants achieving sustained remission using the Ankylosing Spondylitis Disease Activity Score (ASDAS) | 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 |
Months 12, 18, 24, 36, 48, and 54 | |
Secondary | Proportion of UC participants with induction of response within 3 months of initiation of treatment using the partial Mayo Score (PMS) | 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. | Month 3 | |
Secondary | Proportion of UC participants with sustained response after initiation of treatment using the PMS. | 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. | Months 6, 12, 18, 24, 36, 48, and 54 | |
Secondary | Proportion of UC participants achieving clinical remission using the PMS. | 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. | Months 3, 6, 12, 18, 24, 36, 48, and 54 | |
Secondary | Proportion of UC participants with sustained clinical remission using the PMS. | 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. | Months 6, 12, 18, 24, 36, 48, and 54 | |
Secondary | Proportion of UC participants with of loss of clinical response among responders using the PMS. | 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. | Months 6, 12, 18, 24, 36, 48, and 54 | |
Secondary | Proportion of CD participants with induction of response within 3 months of initiation of treatment using the Harvey-Bradshaw Index (HBI) | 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. | Month 3 | |
Secondary | Proportion of CD participants with sustained response after initiation of treatment using the HBI. | 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. | Months 6, 12, 18, 24, 36, 48, and 54 | |
Secondary | Proportion of CD participants achieving clinical remission using the HBI. | 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. | Months 3, 6, 12, 18, 24, 36, 48, and 54 | |
Secondary | Proportion of CD participants with sustained clinical remission using the HBI. | 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. | Months 6, 12, 18, 24, 36, 48, and 54 | |
Secondary | Proportion of CD participants with of loss of clinical response among responders using the HBI. | 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. | Months 6, 12, 18, 24, 36, 48, and 54 | |
Secondary | Change from baseline in the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) score at months 12, 24, and 48 in UC and CD participants. | 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. | Months 12, 24, and 48. |
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