Comparative analysis of adult-onset Still's disease (AOSD) treatments
| ISRCTN | ISRCTN86135778 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN86135778 |
- Submission date
- 12/12/2023
- Registration date
- 14/12/2023
- Last edited
- 14/12/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Plain English summary of protocol
Background and study aims
Adult-onset Still’s disease (AOSD) is a rare autoinflammatory disorder with increased mortality. Complications such as macrophage activation syndrome in continuously active disease carry a high mortality risk. Glucocorticoids (GC) and conventional disease-modifying antirheumatic drugs (DMARDs) are commonly used as first-line therapeutic options as opposed to recently licensed interleukin-1 (IL1)-receptor antagonist anakinra (ANA), neutralizing IL1b-antibody canakinumab (CAN), or non-licensed use of IL-6 receptor antibody tocilizumab (TCZ). However, DMARDs have a considerably slower onset, and GC may result in substantial side-effects such as diabetes mellitus or osteonecrosis of the hips. Our study evaluates potential benefits of biologicals (ANA, CAN, TCZ) as first-line therapeutic options in AOSD.
Who can participate?
Data from AOSD-patients (disease onset) fulfilling the Yamaguchi classification criteria, over 18 years, female/male or divers of the last 15 years of participating centers are included in the study.
What does the study involve?
We plan to retrospectively analyze data from German rheumatology centers (last 15 years), examining both the effectiveness of therapy (percentage of patients in remission) and side effects of different therapies.
What are the possible benefits and risks of participating?
Participating in this study offers the benefit of contributing valuable data to guide treatment decisions for AOSD patients, including insights into treatment responses and potential complications under various treatment options.
Where is the study run from?
When is the study starting and how long is it expected to run for?
January 2023 to January 2024
Who is funding the study?
Investigator initiated and funded
Who is the main contact?
Dr. A. Kernder, anna_kernder@t-online.de
Contact information
Principal Investigator
Hauptstr. 74-76
Meerbusch
40668
Germany
 ORCID ID |
0000-0001-5725-5483 |
|---|---|
| Phone | +49 21 50 / 9 17-0 |
| info@rrz-meerbusch.de |
Public, Scientific
Moorenstraße 5
Düsseldorf
40225
Germany
| ORCID ID |
0000-0002-7742-7526 |
|---|---|
| Phone | +49 02118100 |
| anna_kernder@t-online.de |
Study information
| Study design | Retrospective chart review of AOSD patients from multiple German centers |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital, Laboratory, Medical and other records |
| Study type | Treatment |
| Participant information sheet | Not applicable (retrospective study) |
| Scientific title | Comparison of different treatments in adult-onset Still's disease (AOSD): biologics, glucocorticoids, and conventional disease-modifying antirheumatic drugs (DMARDs) |
| Study acronym | TAST |
| Study objectives | Complication free remission rates are lower in patients initially treated with biological therapy as opposed to DMARD therapy |
| Ethics approval(s) |
Approved 13/09/2023, Ethics Committee of the medical faculty of the University of Duesseldorf (Moorenstr. 5, Düsseldorf, 40225, Germany; +49 211 81-19591; ethikkommission@med.uni-duesseldorf.de), ref: 2023-2423 |
| Health condition(s) or problem(s) studied | Treatments of Adult-onset Still's Disease (AOSD, rheumatic disease) |
| Intervention | Retrospective Observational study Data collected: - Epidemiological data (age at onset, sex, height, weight, comorbidities) - Disease activity data (items of the Pouchot Score, CRP, Ferritin, Leukocyte count, alternatively the EULAR-DAVID score if available in the meantime) - Physician subjective evaluation of “remission” based on chart review - fever yes/no - arthritis yes/no - ASOD-associated rash yes/no - Treatment - Complication of GC use: Diabetes necessitating insulin therapy Gain in body weight (≥ 10%) Osteonecrosis of any joint Psychosis or other psychiatric disease requiring psychopharmacological intervention Hypertension Dyslipidemia requiring therapy with e.g. statins Worsening of bone density > 0,5 SD (T1-4, neck or total hip) Clinical diagnosis of steroid myopathy Skin disease attributed to GC Eye disease attributable to - Serious infection necessitating intravenous antibiotic use - Death - Macrophage activation syndrome - AOSD-associated pneumonitis - ASOD-associated perimyocarditis - Ongoing disease activity requiring switch from DMARD-based to biological therapy |
| Intervention type | Other |
| Primary outcome measure | Sustained remission (definition see below) at week 12 and complication free until week 72 (definition see below). For remission, all of the below must be fulfilled: 1. Physician subjective evaluation of “remission” based on chart review 2. CRP below 10 mg/l 3. No fever during last week 4. No arthritis during last week 5. No ASOD-associated rash during last week For Complication-free (none of the following should have been appeared): 1. Complications of GC use 2. Diabetes necessitating insulin therapy 3. Gain in body weight (≥ 10%) 4. Osteonecrosis of any joint 5. Psychosis or other psychiatric disease requiring psychopharmacological intervention 6. Hypertension > 180 mmHg systolic pressure resulting in change of antihypertensive medication 7. Dyslipidemia requiring therapy with e.g. statins 8. Worsening of bone density > 0,5 SD (T1-4, neck or total hip), preexisting osteoporosis or osteoporosis diagnosed within 2 months of disease onset is not considered to be a GC-related event 9. Clinical diagnosis of steroid myopathy 10. Skin disease attributed to GC, e.g. striae, cutaneous necrosis, relevant subcutaneous bleeding or ulcerations 11. Eye disease attributable to GC (esp. cataract, glaucoma) 12. Serious infection necessitating intravenous antibiotic use 13. Death 14. Development of macrophage activation syndrome, AOSD-associated pneumonitis, ASOD-associated peri myocarditis 15. Ongoing disease activity requiring switch from DMARD-based to biological therapy |
| Secondary outcome measures | 1. Flare-free survival in patients under remission 2. Rate of remission (definition see below) by week 12 and complication free by week 72 3. Retrospective analysis of differences in the glucocorticoid toxicity index (GTI) 4. GC dose reduction (at week 12 and week 72) 5. GC dose reduction by at least 75% compared to disease onset 6. Time to remission 7. Time to complication (definition see above) 8. Complications (definition see above) |
| Overall study start date | 01/01/2023 |
| Completion date | 31/01/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Required sample size per group: 50 |
| Key inclusion criteria | 1. Yamaguchi classification criteria are met 2. Documented clinical visits at onset/flare, by week 12 and week 72 |
| Key exclusion criteria | Not matching the inclusion criteria |
| Date of first enrolment | 15/09/2008 |
| Date of final enrolment | 31/01/2024 |
Locations
Countries of recruitment
- Germany
Study participating centres
Meerbusch-Lank
40668
Germany
Düssseldorf
40225
Germany
Hamburg
20251
Germany
Vogelsang-Gommern
39245
Germany
Erlangen
91054
Germany
Heidelberg
69120
Germany
Hannover
30625
Germany
Bad Nauheim
61231
Germany
Tübingen
72076
Germany
Halle
06120
Germany
Sponsor information
Hospital/treatment centre
Department of Rheumatology
Meerbusch
40668
Germany
| Phone | +49 21 50 / 9 17-0 |
|---|---|
| Stefan.Vordenbaeumen@rrz-merbusch.de |
Funders
Funder type
Other
No information available
Results and Publications
| Intention to publish date | 31/01/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The raw data supporting the conclusions will be made available by the authors on reasonable request. anna_kernder@t-online.de |
Editorial Notes
14/12/2023: Trial's existence confirmed by Ethics Committee of the medical faculty of the University of Duesseldorf.
