Rheumatoid ArthritisSWEFOT-RWEMNCT05051137
Real-World Emulation of the SWEFOT Trial
An observational study of Rheumatoid Arthritis, run by Karolinska Institutet at 1 site in Sweden.
Trial summary
This study will compare rheumatoid arthritis (RA) patients who have been treated in clinical practice with either infliximab or a combination of sulfasalazine and hydroxychloroquine, after having an active disease despite treatment with methotrexate for at least one month. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Infliximab and Sulfasalazine + Hydroxychloroquine
- How many people
- 509 participants
- Where
- 1 siteSweden
- Study dates
- 12 Jan 2006to 16 Nov 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients with rheumatoid arthritis as recorded in the Swedish Rheumatology Quality register (main data source), who initiated one of the two study treatments (infliximab or sulfasalazine + hydroxychloroquine). All eligible patients were included in the study (without any subsequent selection).
Who may be able to join
- Have started methotrexate less than 540 days after RA debut.
- Have used methotrexate for more then 30 days but less than 540 days before study treatment start.
- Have a baseline DAS28-ESR of more than 3.2 at study treatment start.
- Were residents of Sweden within 5 years before study treatment start
Who cannot join
- Have used other DMARDs (antirheumatic drugs) than methotrexate before treatment start
- Have initiated study treatments later than May 2020
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Karolinska Institutet, Department of Medicine Solna, Clinical Epidemiology Unit
Stockholm
About this study
Official title: Comparison of Infliximab With Sulfasalazine/Hydroxychloroquine Initiated After Methotrexate by Rheumatoid Arthritis Patients Treated in Clinical Practice (Real-World Emulation of SWEFOT Trial)
This study will compare rheumatoid arthritis (RA) patients who have been treated in clinical practice with either infliximab or a combination of sulfasalazine and hydroxychloroquine, after having an active disease despite treatment with methotrexate for at least one month. To establish which patients respond to treatment, DAS28-ESR measurements (disease activity score using 28 joints and erythrocyte sedimentation rate) taken at treatment start and nine months thereafter, and the EULAR (European League Against Rheumatism) definition of a "good response" will be employed.
The purpose of the study is to verify if the same conclusion could be reached using data from patients treated in real world clinical practice as in a previous randomized controlled trial comparing the two treatment strategies (SWEFOT -- ClinicalTrials.gov Identifier: NCT00764725).
Read more
Inclusion criteria similar to the ones used in the emulated trial will be applied.
In real clinical practice, patients who receive infliximab may have more severe RA and may also differ in other ways from patients receiving sulfasalazine and hydroxychloroquine. To be able to compare the proportions of responders under each treatment in this "real-world" setting, the data will be re-weighted, so that patient characteristics become balanced between treatment groups.
Read the detailed description
This observational study is designed to verify if the results of a previously conducted randomized controlled trial (SWEFOT -- ClinicalTrials.gov Identifier: NCT00764725) could be replicated with observational data, by emulating the trial protocol as close as possible.
Thus, early rheumatoid arthritis (RA) patients who initiated treatment with infliximab or a combination of sulfasalazine and hydroxychloroquine after at least 30 days of methotrexate will be identified in the Swedish Rheumatology Quality register (SRQ) linked to other Swedish national registers and will be compared. Similar inclusion/exclusion criteria to the ones used in SWEFOT will be applied. Also, in keeping with SWEFOT, the primary outcome is the proportion of patients with a "good EULAR response", measured nine months after study treatment initiation and considering patients who discontinued treatment before this point "non-responders" (i.e. "non-responder imputation" - regardless of the reason for discontinuation). For the combination of sulfasalazine and hydroxychloroquine the start of the second drug in the combination will be considered the study treatment initiation.
Since treatment assignment is not random in observational data, inverse probability of treatment weighting will be applied to balance patient characteristics between treatment cohorts, making them comparable (i.e. exchangeable). For each observation (i.e. patient), the probability of receiving the treatment actually received, conditional on a prespecified list of potential confounders will be estimated by logistic regression modelling and will be used to calculate a weight. Potential confounders included in the model are chosen based on knowledge about factors influencing treatment allocation and observed differences in such characteristics between treatment groups. The list of confounders includes: sex, age, country of origin, year of treatment start, duration of RA at treatment start, rheumatoid factor, disease activity at treatment start measured via: DAS28-ESR (disease activity score using 28 joints and erythrocyte sedimentation rate), CDAI (clinical disease activity index), number of swollen and tender joints, pain assessment (measured on a visual analogue scale) and HAQ-DI (health assessment questionnaire disability index), use of NSAIDs and of glucocorticoids, history of: cancer, diabetes, acute coronary syndrome, stroke, venous thromboembolism, peripheral vascular disease, obstructive respiratory disease, anaemia, psoriasis, neuropathies, pain, osteoporosis, depression or anxiety, joint surgery, retinopathy and hospitalized infections, the number of days spent in hospital within 5 years before treatment start, smoking status.
All data included in this study is extracted from Swedish national registers. In these registers, data is collected routinely, prospectively and independently from any study. Thus, data on baseline characteristics was collected before treatment initiation, while outcome data was recorded after treatment initiation.
The proportion of responders in each group and the ratio between proportions will be estimated using a weighted generalized linear model, specifying a binomial distribution for the dependent variable and a logarithmic identity function. Before analysis, missing data (covariates and outcome) will be imputed using fully conditional specification multiple imputation after non-responder imputation. All data-analysis (from weights estimation to responder-ratio estimation) will be conducted separately in each imputed data-set, the results being subsequently pooled using Rubin's rules.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Infliximab, Sulfasalazine + Hydroxychloroquine
- Keywords
- Rheumatic Diseases
- Medical subject headings
- Arthritis, Rheumatoid, Rheumatic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabBiological
Also called Flixabi, Inflectra, Remicade, Remsima, Zessly
Initiation of infliximab in any dose and frequency of administration. Could be discontinued for safety reasons and replaced by etanercept.
Sulfasalazine + HydroxychloroquineDrug
Also called Salazopyrin (sulfasalazine), Plaquenil (hydroxychloroquine)
Initiation of sulfasalazine and hydroxychloroquine not more than 180 days apart, in any dose and frequency of administration. Any one of the two drugs could be discontinued. while continuing the other, or both could be replaced by cyclosporine, for safety reasons.
| Study group | Role | What they receive |
|---|---|---|
| Infliximab initiators | Rheumatoid arthritis patients initiating infliximab after treatment with methotrexate for a minimum of 30 days. Receives: Biological: Infliximab | |
| Sulfasalazine + Hydroxychloroquine initiators | Rheumatoid arthritis patients initiating sulfasalazine and hydroxychloroquine after treatment with methotrexate for a minimum of 30 days. Receives: Drug: Sulfasalazine + Hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Good EULAR Response
The proportion of patients remaining on treatment and achieving a "good EULAR response" defined as a DAS28-ESR ≤ 3.2 at evaluation and a decrease > 1.2 units compared to the value at treatment initiation.
Measured: 9 months after study treatment initiation
Secondary outcomes (1)
Good or Moderate EULAR Response
The proportion of patients remaining on treatment and achieving a "good or moderate EULAR response" defined as a DAS28-ESR ≤ 5.1 at evaluation and a decrease > 0.6 units compared to the value at treatment initiation, or a DAS28-ESR > 5.1 at evaluation and a decrease > 1.2 units compared to treatment start.
Measured: 9 months after study treatment initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2021
- Study start12 Jan 2006
- Primary completion16 Nov 2020
- Study completion16 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 509 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Harvard Medical School (HMS and HSDM)
- Responsible party
- Principal investigator, Thomas Frisell, Karolinska Institutet
- Investigators
- Thomas Frisell, PhD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05051137
- Sponsor's protocol ID
- SWEFOT-RWEM
- Acronym
- SWEFOT-RWEM
- Status last verified
- Sep 2021
- First submitted
- 10 Sep 2021
- Last updated
- 28 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is not a plan to make IPD available
Publications
van Vollenhoven RF, Ernestam S, Geborek P, Petersson IF, Coster L, Waltbrand E, Zickert A, Theander J, Thorner A, Hellstrom H, Teleman A, Dackhammar C, Akre F, Forslind K, Ljung L, Oding R, Chatzidionysiou A, Wornert M, Bratt J. Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial. Lancet. 2009 Aug 8;374(9688):459-66. doi: 10.1016/S0140-6736(09)60944-2.
PubMed 19665644van Vollenhoven RF, Geborek P, Forslind K, Albertsson K, Ernestam S, Petersson IF, Chatzidionysiou K, Bratt J; Swefot study group. Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial. Lancet. 2012 May 5;379(9827):1712-20. doi: 10.1016/S0140-6736(12)60027-0. Epub 2012 Mar 29.
PubMed 22464340
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Infliximab With Sulfasalazine/Hydroxychloroquine Initiated After Methotrexate by Rheumatoid Arthritis Patients Treated in Clinical Practice (Real-World Emulation of SWEFOT Trial)
- ClinicalTrials.gov ID
- NCT05051137
- Acronym / sponsor ID
- SWEFOT-RWEM / SWEFOT-RWEM
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatic Diseases
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 509 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Harvard Medical School (HMS and HSDM)
- Study start
- 12 Jan 2006 (actual)
- Primary completion
- 16 Nov 2020 (actual)
- Study completion
- 16 Nov 2020 (actual)
- First posted
- 21 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will compare rheumatoid arthritis (RA) patients who have been treated in clinical practice with either infliximab or a combination of sulfasalazine and hydroxychloroquine, after having an active disease despite treatment with methotrexate for at least one month. To establish which patients respond to treatment, DAS28-ESR measurements (disease activity score using 28 joints and erythrocyte sedimentation rate) taken at treatment start and nine months thereafter, and the EULAR (European League Against Rheumatism) definition of a "good response" will be employed.
The purpose of the study is to verify if the same conclusion could be reached using data from patients treated in real world clinical practice as in a previous randomized controlled trial comparing the two treatment strategies (SWEFOT -- ClinicalTrials.gov Identifier: NCT00764725).
Inclusion criteria similar to the ones used in the emulated trial will be applied.
In real clinical practice, patients who receive infliximab may have more severe RA and may also differ in other ways from patients receiving sulfasalazine and hydroxychloroquine. To be able to compare the proportions of responders under each treatment in this "real-world" setting, the data will be re-weighted, so that patient characteristics become balanced between treatment groups.
Detailed description
This observational study is designed to verify if the results of a previously conducted randomized controlled trial (SWEFOT -- ClinicalTrials.gov Identifier: NCT00764725) could be replicated with observational data, by emulating the trial protocol as close as possible.
Thus, early rheumatoid arthritis (RA) patients who initiated treatment with infliximab or a combination of sulfasalazine and hydroxychloroquine after at least 30 days of methotrexate will be identified in the Swedish Rheumatology Quality register (SRQ) linked to other Swedish national registers and will be compared. Similar inclusion/exclusion criteria to the ones used in SWEFOT will be applied. Also, in keeping with SWEFOT, the primary outcome is the proportion of patients with a "good EULAR response", measured nine months after study treatment initiation and considering patients who discontinued treatment before this point "non-responders" (i.e. "non-responder imputation" - regardless of the reason for discontinuation). For the combination of sulfasalazine and hydroxychloroquine the start of the second drug in the combination will be considered the study treatment initiation.
Since treatment assignment is not random in observational data, inverse probability of treatment weighting will be applied to balance patient characteristics between treatment cohorts, making them comparable (i.e. exchangeable). For each observation (i.e. patient), the probability of receiving the treatment actually received, conditional on a prespecified list of potential confounders will be estimated by logistic regression modelling and will be used to calculate a weight. Potential confounders included in the model are chosen based on knowledge about factors influencing treatment allocation and observed differences in such characteristics between treatment groups. The list of confounders includes: sex, age, country of origin, year of treatment start, duration of RA at treatment start, rheumatoid factor, disease activity at treatment start measured via: DAS28-ESR (disease activity score using 28 joints and erythrocyte sedimentation rate), CDAI (clinical disease activity index), number of swollen and tender joints, pain assessment (measured on a visual analogue scale) and HAQ-DI (health assessment questionnaire disability index), use of NSAIDs and of glucocorticoids, history of: cancer, diabetes, acute coronary syndrome, stroke, venous thromboembolism, peripheral vascular disease, obstructive respiratory disease, anaemia, psoriasis, neuropathies, pain, osteoporosis, depression or anxiety, joint surgery, retinopathy and hospitalized infections, the number of days spent in hospital within 5 years before treatment start, smoking status.
All data included in this study is extracted from Swedish national registers. In these registers, data is collected routinely, prospectively and independently from any study. Thus, data on baseline characteristics was collected before treatment initiation, while outcome data was recorded after treatment initiation.
The proportion of responders in each group and the ratio between proportions will be estimated using a weighted generalized linear model, specifying a binomial distribution for the dependent variable and a logarithmic identity function. Before analysis, missing data (covariates and outcome) will be imputed using fully conditional specification multiple imputation after non-responder imputation. All data-analysis (from weights estimation to responder-ratio estimation) will be conducted separately in each imputed data-set, the results being subsequently pooled using Rubin's rules.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Infliximab initiators | – | Biological: InfliximabRheumatoid arthritis patients initiating infliximab after treatment with methotrexate for a minimum of 30 days. |
| Sulfasalazine + Hydroxychloroquine initiators | – | Drug: Sulfasalazine + HydroxychloroquineRheumatoid arthritis patients initiating sulfasalazine and hydroxychloroquine after treatment with methotrexate for a minimum of 30 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients with rheumatoid arthritis as recorded in the Swedish Rheumatology Quality register (main data source), who initiated one of the two study treatments (infliximab or sulfasalazine + hydroxychloroquine). All eligible patients were included in the study (without any subsequent selection).
Key inclusion criteria (4 listed)
- Have started methotrexate less than 540 days after RA debut.
- Have used methotrexate for more then 30 days but less than 540 days before study treatment start.
- Have a baseline DAS28-ESR of more than 3.2 at study treatment start.
- Were residents of Sweden within 5 years before study treatment start
Key exclusion criteria (2 listed)
- Have used other DMARDs (antirheumatic drugs) than methotrexate before treatment start
- Have initiated study treatments later than May 2020
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InfliximabAlso: Flixabi, Inflectra, Remicade, Remsima, ZesslyInitiation of infliximab in any dose and frequency of administration. Could be discontinued for safety reasons and replaced by etanercept. | Biological | Infliximab initiators |
| Sulfasalazine + HydroxychloroquineAlso: Salazopyrin (sulfasalazine), Plaquenil (hydroxychloroquine)Initiation of sulfasalazine and hydroxychloroquine not more than 180 days apart, in any dose and frequency of administration. Any one of the two drugs could be discontinued. while continuing the other, or both could be replaced by cyclosporine, for safety reasons. | Drug | Sulfasalazine + Hydroxychloroquine initiators |
Primary outcome
Good EULAR Response
Time frame: 9 months after study treatment initiation
The proportion of patients remaining on treatment and achieving a "good EULAR response" defined as a DAS28-ESR ≤ 3.2 at evaluation and a decrease > 1.2 units compared to the value at treatment initiation.
1 secondary outcome
Good or Moderate EULAR Response
Time frame: 9 months after study treatment initiation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2021.
- Background: PubMed 19665644van Vollenhoven RF, Ernestam S, Geborek P, Petersson IF, Coster L, Waltbrand E, Zickert A, Theander J, Thorner A, Hellstrom H, Teleman A, Dackhammar C, Akre F, Forslind K, Ljung L, Oding R, Chatzidionysiou A, Wornert M, Bratt J. Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial. Lancet. 2009 Aug 8;374(9688):459-66. doi: 10.1016/S0140-6736(09)60944-2.
- Background: PubMed 22464340van Vollenhoven RF, Geborek P, Forslind K, Albertsson K, Ernestam S, Petersson IF, Chatzidionysiou K, Bratt J; Swefot study group. Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial. Lancet. 2012 May 5;379(9827):1712-20. doi: 10.1016/S0140-6736(12)60027-0. Epub 2012 Mar 29.
- Individual participant dataSharing planned: No. There is not a plan to make IPD available
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Frisell, PhD principal investigator
Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rheumatoid Arthritis, run by Karolinska Institutet at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Good EULAR Response (time frame: 9 months after study treatment initiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05051137, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2021.