As this is an explorative design, no formal hypothesis is made. However, our sample size is based on a difference of 2.5% or more in cumulative incidence of serious infections when continuing IA, hypothesizing that patients who continue their IA in…
ID
Source
Brief title
Condition
- Autoimmune disorders
Health condition
Rheumatoid arthritis
Psoriatic arthritis
Axial spondyloarthritis
Immune mediated inflammatory diseases
Inflammatory rheumatic diseases
Research involving
Sponsors and support
Intervention
- Other intervention
Outcome measures
Primary outcome
Proportion of participants with a serious infection, i.e. grade 3 or higher (according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0).
Secondary outcome
- Patient characteristics: age, gender, weight, length, smoking habits, education, paid work characteristics, health care worker yes/no, having received influenza vaccination yes/no, other vaccinations, marital status, co-morbidities (cardiovascular disease, hypertension, diabetes) - Disease characteristics: diagnosis/diagnoses, year of diagnosis, history of severe infection - Treatment characteristics: (number of) previously used IA drugs, current medication, number of consultations with care providers - Medication use over time: use of IA medication (including prednisone), NSAIDs and ACE inhibitors during study period - Adverse events: occurrence of other (serious) adverse events during the study period. - Behavioural and environmental characteristics: compliance to Dutch COVID regulations (work at home if possible, social distancing) yes/no, positive or suspected COVID-infection within household yes/no. - Incidence of clinical infection (later validated and expanded using chart review, see definition in table 2), independent of location, type of infection, or severity. - Infection characteristics: severity (Grade), infection duration (days until resolution), recurrence of infection, antibiotics use, hospital admission (+duration), surgery, IC-admission (+ duration, use of vasoconstrictive medicine), death - IMID-related flares, defined by the patient (‘are you currently experiencing, or did you experience a flare-up of your disease’ yes/no) - Direct medical costs (medication, consultations with general practitioner/specialists, hospitalization, intensive care admission, surgery)
Background summary
Immunomodulatory agents (IA) are widely used (>200,000 patients in the Netherlands) for the treatment of patients with immune-mediated inflammatory diseases (IMIDs) including rheumatoid arthritis, psoriatic arthritis, axial spondylarthritis, psoriasis and inflammatory bowel disease, and they are in general associated with a modestly increased risk of infection. However, it is not clear what risk factors for infection are, and whether it is wise to temporary interrupt IA treatment during an infection. Recently, the COVID-19 pandemic has dramatically increased the urgency to provide answers to these questions, especially since, surprisingly, some IA seem to be effective treatment against COVID-19. Therefore, the objectives of this study are to: 1) To assess the effect of continuation of IA treatment in IMID patients during an infection compared to temporary interruption of the IA treatment with regard to serious infection, and 2) to study the incidence and risk factors for infection in IMID patients using IA, with special attention for COVID-19. This study is a two arm, open-label pragmatic, explorative randomized controlled strategy study, among IMID patients using IA in the Netherlands. Adult patients with rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, psoriasis and inflammatory bowel disease using IA (except monotherapy rituximab or glucocorticoids) in any dose without a current infection will be included and randomized into either the intervention or control group. The intervention consists of continued IA treatment and the control condition is interruption of IA treatment until the infection is resolved, all in addition to standard of care. Main study parameters/endpoints: The primary outcome is serious infection (resulting in hospitalization, intravenous antibiotics, admission to the intensive care or death)
Study objective
As this is an explorative design, no formal hypothesis is made. However, our sample size is based on a difference of 2.5% or more in cumulative incidence of serious infections when continuing IA, hypothesizing that patients who continue their IA in case of an infection experience less severe infections compared to patient who temporarily interrupt IA.
Study design
Patients will be followed for 12 months, receiving questionnaires at baseline and one each following month. If a patient experiences an infection at t = 12 months, he/she will be followed until the infection has passed. In addition, data will be collected in case of an infection.
Intervention
Age
Inclusion criteria
- Clinical diagnosis of at least one of the following IMIDs: Rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), psoriasis (PsO) or inflammatory bowel disease (IBD) (i.e. Crohns disease (CD) or ulcerative colitis (UC). - Age ≥ 16 years - Using one or more of the following immunomodulating agents (IA) from table 1 in any dose. Monotherapy rituximab and glucocorticoids are exempts because rituximab cannot be stopped due to long half-life time and post pharmacokinetic effects on b-cell depletion, and glucocorticoids because stopping is associated with secondary hypocortisolism. - Not experiencing any clinical infection at time of inclusion (based on check in electronic health record and as reported by patient at inclusion). - Ability to read and communicate well in Dutch
Exclusion criteria
- Use of the following immunomodulating agents in monotherapy and through intravenous administration: rituximab, tocilizumab or abatacept. This because the contrast between stopping and continuation is expected to be low, as the treatment intervals are high, and intravenous medication is not easily provided in case of hospital admission. - Use of glucocorticoids (GC) in monotherapy, because stopping of GC is not feasible due to risk of GC use induced hypocortisolism - Not willing to be randomized to either intervention or control condition. - Not being able to be followed for 12 months, because of planned relocation or short life expectancy.
Design
Recruitment
IPD sharing statement
Plan description
p/a Radboudumc, huispost 628,
Postbus 9101
6500 HB Nijmegen
024 361 3154
commissiemensgebondenonderzoek@radboudumc.nl
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL8922 |
| CCMO | NL73479.091.20 |
| OMON | NL-OMON54899 |