Efficacy of Rituximab in Reducing Glucocorticoid Exposure in Patients with Relapsing Polymyalgia Rheumatica: A Randomized Controlled Trial

The primary objective of the study is to evaluate the **efficacy** of treatment with **rituximab** in patients with relapsing **polymyalgia rheumatica** compared to placebo. This is clinically relevant as it aims to determine whether rituximab can effectively reduce the need for glucocorticoid exposure, which is a common treatment for this condition but is associated with significant side effects. The study does not list any secondary objectives.

The clinical trial focuses on evaluating the efficacy of **rituximab** in patients with relapsing **polymyalgia rheumatica**. The study population includes both male and female participants, with an age range encompassing adults and older adults. The trial does not involve a vulnerable population. Participants were selected based on specific inclusion criteria, such as a clinical diagnosis of polymyalgia rheumatica according to the 2012 EULAR/ACR classification criteria, re-emerging symptoms, and elevated ESR or CRP levels. Additionally, participants must be unable to reduce their glucocorticoid dose below 5mg/day prednisolone or equivalent. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the **efficacy** of **rituximab** in patients with relapsing **polymyalgia rheumatica** compared to a placebo. This is a **randomized**, **double-blind**, and **controlled** trial, categorized as a Phase III/IV therapeutic clinical trial. The trial is expected to last until April 2026, with recruitment having commenced in February 2023. Participants will be involved in the study for a period of up to two years, with the primary endpoint being the proportion of patients in glucocorticoid-free remission one year after treatment with rituximab compared to placebo.

The study will include several visits, starting with a screening visit to confirm eligibility based on criteria such as a clinical diagnosis of polymyalgia rheumatica according to the 2012 EULAR/ACR classification criteria, re-emerging symptoms, and elevated ESR or CRP levels. Participants unable to reduce glucocorticoid dose below 5mg/day prednisolone or equivalent will also be considered. Follow-up visits will occur at regular intervals to assess secondary endpoints, including the proportion of patients in glucocorticoid-free remission at various time points, the number of disease relapses, and changes in patient-reported outcomes.

The end-of-study visit will evaluate the long-term outcomes, including the proportion of patients in remission two years after rituximab or placebo infusion. Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The trial will also monitor the frequency and types of adverse events, particularly those related to glucocorticoids and rituximab, throughout the 52-week study period.

The clinical trial involves the administration of **rituximab**, an experimental medication, to evaluate its efficacy in patients with relapsing **polymyalgia rheumatica**. Rituximab is provided in the form of a **solution for infusion** and is administered **intravenously**. The maximum daily dose of rituximab is 1000 mg, with a total maximum dose of 1500 mg over the course of the treatment period. The treatment period is limited to a maximum of one month. Rituximab is a protein-based therapeutic agent, specifically classified under the category of "Protein - Other". The administration of rituximab is monitored to ensure compliance with the dosing schedule and to assess the therapeutic outcomes in the study participants.

In addition to the experimental treatment with rituximab, a **placebo** is used as a comparator in this clinical trial. The placebo is administered in a manner consistent with the rituximab treatment to maintain the integrity of the study design. The use of a placebo allows for the evaluation of rituximab's efficacy by providing a baseline for comparison. Participant compliance with the administration of both rituximab and placebo is closely monitored throughout the trial to ensure adherence to the protocol and to accurately assess the treatment's impact on the condition being studied.

The efficacy of rituximab in patients with relapsing **polymyalgia rheumatica** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of patients achieving glucocorticoid (GC) free remission one year after treatment with rituximab compared to placebo. Secondary endpoints include the proportion of patients in GC free remission at week 21, and at 1.5 and 2 years post-treatment. Additional secondary endpoints involve the proportion of patients maintaining low dose GC remission (≤5mg/day) at various timepoints, including week 21, week 52, 1.5 years, and 2 years.

Other secondary endpoints include the PMR Activity Score (PMR-AS) at each visit, the number and proportion of disease relapses or recurrences up to 52 weeks and 2 years, and the time from baseline to GC free remission and to relapse. The cumulative GC dose at 52 weeks, 1.5 years, and 2 years will also be evaluated. The study will assess the proportion of patients requiring retreatment with rituximab or placebo, as well as those starting other treatments such as methotrexate, leflunomide, tocilizumab, or sarilumab. Sex differences in GC-remission frequencies and adverse events, changes in patient-reported outcomes related to pain, fatigue, stiffness, and physical function, and medical consumption and productivity loss will be analyzed. The modified glucocorticoid toxicity index, excluding bone mineral density scans, will be used to assess changes in toxicity. The frequency and types of adverse events, particularly those related to GC and rituximab, will be monitored throughout the 52-week study period.