Rituximab Effect on Decreasing glUcoCorticoid Exposition in PolyMyalgia Rheumatica Patients Experiencing a PMR Relapse

Polymyalgia rheumatica (PMR) is one of the most prevalent inflammatory
rheumatic diseases among people older than 50 years. It is characterized by
pain and stiffness of the neck, bilateral shoulder and hip girdle and is often
associated with elevated inflammatory parameters. Untreated, it leads to a
significant and long-term reduction in quality of life. Glucocorticoids (GC)
are the cornerstone of treatment, but have several drawbacks. First, only a
minority of patients achieves GC-free remission after one or two years. Second,
GC-related adverse events (AE) occur in a large portion of patients, up to 65%
depending on the GC dosage. When patient relapse intensification and longer
duration of GC treatment is needed resulting in more GC related AE. Therefore,
the search for GC-sparing agents is high on the research agenda. Although the
exact pathogenesis of PMR is not known, there are several indications that
B-cells have a role in PMR. This make Rituximab (RTX), a chimeric monoclonal
antibody targeting B-cells via CD-20, a possible candidate. An exploratory
proof of concept RCT demonstrated that a significantly higher proportion of PMR
patients treated with RTX achieved GC-free remission at 21 and 52 weeks
compared to placebo. These effects appeared to be larger in new PMR patients
than in relapsing patients. The efficacy of RTX in patients with relapsing PMR
needs confirmation and should therefore be further investigated in a larger
study with longer follow up.

This study has been transitioned to CTIS with ID 2024-513545-37-00 check the CTIS register for the current data.

The main objective is to study the efficacy of treatment with RTX in patients
with relapsing PMR compared to placebo.

A total of 174 patients wil participate in this study. Patients will be
randomized 1:1 to either RTX of placebo. At baseline treatment consists of
1000mg iv RTX with usual premedication, placebo group will receive 0mg iv RTX
with similar oral pre-medication as the intervention group. Additionally at
baseline all patients receive prednisolone 15mg/day or 10mg/day in a 17-week
accelerated tapering protocol with the possibility of increasing GC dose in
case of non response or relapse. A lower dose of prednisolone can be chosen if
a patient relapses on a lower dose, resembling clinical practice more closely
and reducing unnecessary GC-use. The choice is based on rheumatologist
judgement and shared decision making with the patient.
Patients with a need for treatment intensification (based on relapse or
increase of GC dose) will receive an extra dosage of 500mgiv RTX (or 0mg iv RTX
in placebo group) after 24 weeks, unless adverse events occurred at infusion
hampering the possibility of retreatment.

Study visits take place at 4, 12, 21, 32 and 52 weeks. Visits at week 4,12 and
32 can be performed digitally or by telephone if preferred by patients and
treating phycisian. Disease activity will be measured at every visit using
PMR-AS. PMR-AS is defined by CRP, duration of morning stiffness (minutes),
elevation upper limb score (EUL) and the physicians and patients visual
analogue scale(VAS). Remission is defined as PMR-AS < 10. At every study visit
patients will be asked to fill in a few questionnaires regarding daily
activities and quality of life.

Patients will be randomized 1:1 to either RTX of placebo. At baseline
treatment consists of 1000mg iv RTX with usual premedication, placebo group
will receive 0mg iv RTX with similar oral pre-medication as the intervention
group. Additionally at baseline all patients receive prednisolone 15mg/day or
10mg/day in a 17-week accelerated tapering protocol with the possibility of
increasing GC dose in case of non response or relapse. A lower dose of
prednisolone can be chosen if a patient relapses on a lower dose, resembling
clinical practice more closely and reducing unnecessary GC-use. The choice is
based on rheumatologist judgement and shared decision making with the patient.

In current practice, patients with PMR visit the outpatient clinic every two,
three or six months, including measurement of disease activity and collecting
blood samples. For this study patients will visit the clinic at baseline, 32
and 52 weeks. Other visits can be performed digitally of by phone if preferred
by patients and treating physician. Blood sampling is done in accordance to
regular practice. Questionnaires entailing a range of domains take a maximum of
30 minutes at every visit.
Possible risks when participating in this study include a chance of temporary
increase of disease activity because of the accelerated GC tapering schema,
especially in the placebo group. However, patients will be instructed to
contact the research physician when this happens and he/she can immediately act
upon this by increasing the GC dose. Other possible adverse effects can be
related to RTX treatment, including dose-dependent risk of infection or
infusion related side effects. Based on our previous experience with RTX we
expect a minimal risk for patients treated with RTX. We expect the risk for
COVID-19 infection to be minimal because most patients will be vaccinated, RTX
treatment initially consist of a one-time dosage and if retreatment is needed a
lower dosage is given. Also patients can benefit from the reduced dose of GC
and a lower chance of GC-related side effects.