Immune Related Rheumatological Adverse Events.
Data collection from patients with cancer to evaluate rheumatological adverse events in patients treated with immune-checkpoint inhibitors.

Advances in systematic anticancer treatment using the patient's own immune
system through immunotherapy are the standard of care in an increasing number
of indications. Through blocking immune checkpoints (PD-1, PD-L1, CTCLA-4 and
Lag-3), T-cell activity can be increased, thereby enhancing immune response. A
notable side-effect of these treatments is an increasing number of
immune-related side-effects (irAE's), of which some (10-43%) are very similar
to known rheumatological diseases. These adverse events result in pain and
functional impairment at short term and can potentially lead to permanent
damage to specific tissues in case of longstanding/relapsing inflammatory
activity with significant reduction of quality of life (QoL). Due to the
relatively recent increase in clinical use of these treatments there is a
current lack of diagnostic and clinical research and resultant guidelines. This
study will therefore attempt to collect a broad variety of diagnostic, clinical
and treatment data.

This study has been transitioned to CTIS with ID 2024-516631-27-00 check the CTIS register for the current data.

The evaluation of R-IrAE's after ICI therapy, specifically incidence, treament
of R-IrAE's, response to said treatment, baseline and follow-up serology
(general and symptom specific) to be combined with quality of life assessment
and symptom specific questionnaires in a prospective cohort study in a
multicenter setting.

The main study consists of 3 cohorts, in which prospective clinical data will
be collected in a multicenter setting, with a substudy consisting of a further
3 cohorts (2 subgroups of main study cohorts, 1 comparator cohort) subjected to
further evaluation. Specific information (clinical, serological, imaging,
oncological and treatment-related) will be collected from patients who develop
a R-irAE (broad rheumatological spectrum of disease manifestations as defined
below) during or after ICI therapy within a period of 1 year after start of
treatment. Patients with or without a preexisting rheumatological disease will
be divided between specific cohorts. A combined database will be created for
the gathered information in preparation for the planned analyses. Similar data
collection is applicable for all participating centers and an expanded dataset,
collected only at the main study center, Amsterdam UMC (AUMC). Any additional
data concerning clinical status, imaging, tissue biopsies and serology
collected during clinical care will also be included where available.
Additionally, a substudy will be performed to collect specific histological and
imaging data in patients with arthritis as the R-irAE. These data will be
compared with data extracted from patients with de novo rheumatoid arthritis
(RA), as the comparator cohort. In this substudy, the immunological phenotype
characterizing arthritis irAE will be investigated via further serological
sampling, as well as histological sampling of synovial tissue and whole
body18F-FDG PET-CT imaging. This substudy will only include patients at the
AUMC (monocenter), either locally included or through specific referrals from
other participating centers.

Patients will be asked to fill in questionnaires or answer questions by the
researchers, in addition to a physical exam and serological evaluations. As
these blood draws will be planned to coincide with regular, planned venous
blood draws before and during treatment, this will not increase their burden
beyond removing up to a maximum 280ml of blood over the course of the study. In
the subgroups S2.1 and S3.1(part of the substudy focused on arthritis), N=15 (
N=10 from S2.1, N=5 from S3.1) patients are additionally subjected to a 18F-FDG
PET-CT scan and an synovial biopsy of an affected joints. This will be combined
where possible with the first study visit or planned within 1 week of the
baseline assessment. The total radiation burden per patient will be around
5.4mSv, which is within the range of risk category IIb of the IRCP 62
guidelines: acquisition of knowledge aimed at prevention or cure of disease.
Attendant to undergoing the synovial biopsy is a small risk of bleeding,
longstanding pain, haemarthros, swelling of the joint (all less than 1,5%)
after synovial biopsy.
The benefits of collecting biological and immunological information about the
nature of irAE-arthritis outweigh the described very low risks of PET-CT
scanning and synovial biopsie.