1. To determine biomarkers of response and non-response to treatment for active SLE in a prospective study where patients will be allocated to therapy according to current clinical practice and the EULAR guidelines (response biomarker study; 3TR SLE…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Flare biomarker study: Proportion of patients developing a flare within 24
months of follow-up, defined as a new BILAG A or B in any clinical domain. The
impact of the presence of anti-SARS-CoV-2 antibodies of different isotypes
(IgA, IgG, IgM) on this outcome will be addressed.
- Response biomarker study: BICLA response at week 52 from baseline.
Secondary outcome
- Flare biomarker study: Proportion of patients developing a flare within 24
months of follow-up, defined according to the SELENA-SLEDAI Flare Index (SFI).
The impact of the presence of anti-SARS-CoV-2 antibodies of different isotypes
(IgA, IgG, IgM) on this outcome will be addressed.
- Reponse biomarker study: SLE Responder Index (SRI)-4, SRI-5 and SRI-6
response (at all time points); Time to BICLA response and SRI response; failure
to attain BICLA response or SRI-4, SRI-5 and SRI-6 response (at all time
points); Change in SLEDAI-2K scores, Physician*s Global Assessment (PhGA, on a
scale 0-3) and Patient*s Global Assessment (PGA, on a 0-10 VAS) (at all time
points); LLDAS, and its individual components (at all time points); Remission
according to DORIS, and its individual components (at all time points); Flare,
based on BILAG (any new worsening in BILAG, or any new BILAG A or B) or
SELENA-SLEDAI Flare Index (SFI) (at all time points); Renal
response/non-response, according to the 2019 EULAR/EDTA recommendations;
Organ-specific outcome measures (e.g. CLASI for mucocutaneous involvement, 44
joint assessment of tender and swollen joints for articular involvement) (at
all time points); Worsening in SLICC/ACR Damage Index (SDI) score (at week 52);
Health-related quality of life (HRQoL), assessed with EQ-5D-5L, FACIT-F,
Medical Outcomes Study 36-item Short Form health survey (SF-36), Epworth
Sleepiness scale (ESS) and Lupus-QoL (at week 26 and week 52); Impact of
anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment
of or time to BICLA, SRI, LLDAS and DORIS, change in SLEDAI-2K, PhGA, PGA and
SDI scores, change in organ specific index scores, and HRQoL outcomes.
Background summary
3TR (Taxonomy, Treatment, Targets and Remission) is a transdisciplinary
consortium with the aim to perform a longitudinal multi-dimensional molecular
analysis in patients with autoimmune, allergic and inflammatory diseases.
Systemic lupus erythematosus (SLE) is one of the chronic disorders that will be
investigated for possible shared biomolecular pathways.
SLE is a complex and heterogeneous autoimmune disease of only partially
unraveled etiology, characterized by the production of autoantibodies, tissue
deposition of immune complexes, and eventually tissue damage across multiple
organ systems. The natural history of SLE is characterized by relapses or
flares alternated with periods of remission. Flares are associated with accrual
of organ damage independently of other risk factors, both contributing to a
considerable morbidity. Although remission is the desirable target of SLE, a
failure to achieve at least the so-called Lupus Low Disease Activity State
(LLDAS) increases the risk of subsequent damage or flare. Despite the fact that
important advances have been achieved over the years regarding the
understanding and management of the disease, SLE pathogenesis still is poorly
understood. Still, a major advance in the treatment of SLE and the prevention
of its complications is expected to come from a clear comprehension of the
mechanisms of response to therapies or, conversely, of escape to sustained
response to them.
There remains an unmet need of identification of patients who can be expected
to best benefit from SLE therapies. By analyzing biomolecular characteristics,
we aim to identify new biomarkers to predict response and non-reponse to
current therapies, and predict flares. More insight in the pathogenesis will
offer future possibilities for the identification of new treatments and will
contribute to improved diagnostics and monitoring in SLE through personalized
therapy.
Study objective
1. To determine biomarkers of response and non-response to treatment for active
SLE in a prospective study where patients will be allocated to therapy
according to current clinical practice and the EULAR guidelines (response
biomarker study; 3TR SLE 2).
2. To determine biomarkers of flare in patients with a clinically stable or
quiescent SLE over an observational period of a maximum of 24 months (flare
biomarker study; 3TR SLE 1).
Study design
This is a European observational cohort study, in which patients from multiple
European centers participating in 3TR will be recruited for a longitudinal
clinical follow-up and collections of several samples (e.g. blood, urine,
saliva, and relevant tissues) from the same individual at multiple time points.
For the SLE study a two-step study has been designed, and comprises:
1. The flare biomarker study (3TR SLE 1) is considered a *feeding* phase before
the main part, but patients who meet the inclusion criteria for 3TR SLE 2 will
be directly included in this second study.
2. The response biomarker study (3TR SLE 2), which is the main part.
Study burden and risks
There are 2-8 time points of this study depending on patient characteristics.
If possible, the study visits will be planned on the same day as a regular
clinical visit. Collection of blood, urine, stool, and saliva only causes a
small inconvenience. Completing the questionnares will take a maximum of 30
minutes per visit. Patients can additionally consent to undergo biopsies of the
skin (collection of kidney biopsy is standard care); these procedures carry
only a small risk in terms of pain, infection and bleeding, which in most cases
can be treated with painkillers, antibiotics or adequate pressure on the wound.
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
- Flare biomarker study:
1. Age at the time of inclusion >= 18 years.
2. Diagnosis of SLE according to the EULAR/ACR criteria.
3. BILAG C, D or E only.
4. No restriction regarding current or previous therapies, except for
hydroxychloroquine (HCQ) or chloroquine treatment which should be administered
unless contraindicated or documented intolerance in the past.
- Response biomarker study:
1. Age at the time of inclusion >= 18 years.
2. Diagnosis of SLE according to the EULAR/ACR criteria.
3. Patients should have at least one of the following: i. active arthritis,
attributed to SLE (BILAG A or B in the musculoskeletal domain). ii. active skin
disease, attributed to SLE (BILAG A or B in the mucocutaneous domain). iii.
active biopsy-proven lupus nephritis (LN; ISN/RPS class III, IV or V), with or
without extrarenal organ involvement. iv. active CNS involvement as a main
manifestation (with or without other organ involvement) along with initiation
of new treatment for CNS involvement (BILAG A or B in the neuropsychiatric
domain).
4. Stable standard therapy for at least 30 days, including hydroxychloroquine
(HCQ) or chloroquine treatment, unless contraindicated or documented
intolerance.
Exclusion criteria
- Flare biomarker study:
1. Pregnancy (at baseline).
2. Initiation or intensification of immunosuppressive therapy or a prednisone
equivalent dose of > 10 mg/day within 30 days prior to baseline.
- Response biomarker study:
1. Serological activity only without signs of clinically active disease.
2. Pregnancy (at baseline).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL77212.029.22 |