Randomized Controlled Trial Evaluating Systemic Corticosteroids Versus Placebo in Acute Severe Erythema Multiforme: Prednisone and Methylprednisolone Acetate Analysis

The primary objective of this study is to demonstrate that a short course (12 days) of **systemic corticosteroids (SCS)** could alleviate pain and improve food intake without the need for rescue therapy, as compared with placebo, in the acute established phase of severe **erythema multiforme (EM)**. This is clinically relevant as it aims to provide an effective treatment strategy for managing pain and nutritional intake in patients with severe EM, potentially reducing the need for additional interventions.

Secondary objectives include:

• Evaluating the impact of SCS on the duration of clear or almost clear healing of all sites.
• Assessing the impact of SCS on the duration of fever.
• Comparing the length of hospital stay between the two groups.
• Comparing the consumption of level III analgesics between the two groups.
• Comparing pain intensity between the two groups.
• Comparing the resumption of chopped or solid food intake between the two groups.
• Comparing the rate of rescue therapies (IV methylprednisolone at 1mg/kg/day with discontinuation of the current treatment in both arms) between the two groups.
• Evaluating the impact of SCS on the rate of sequelae affecting the eyes, oral cavity, genital area, esophagus, and respiratory tract.
• Comparing the rate of adverse events between the two groups.
• Evaluating the quality of life.

The clinical trial involves participants diagnosed with **erythema multiforme** (EM) in its severe form, managed at the hospital. The study population includes both male and female subjects, aged 15 years and older, with a weight range between 30 kg and 150 kg. Participants are required to have a clinical diagnosis of severe EM, characterized by typical skin lesions or mucosal involvement, and must be experiencing a disease flare lasting up to 5 days. The trial does not focus on a vulnerable population, and participants must be affiliated with a social security scheme and capable of providing written informed consent. 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 a short course of systemic corticosteroids (SCS) compared to a placebo in the treatment of severe **erythema multiforme** (EM) during its acute established phase. This is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias. The trial is expected to last until June 2028, with recruitment starting in February 2025. The primary objective is to demonstrate that a 12-day course of SCS can alleviate pain and improve food intake without the need for rescue therapy.

Participants will be involved in the study for a maximum of 12 days, corresponding to the treatment period. The trial includes several key visits: an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor progress and assess endpoints. The end-of-study visit will evaluate the overall outcomes and any adverse events. Inclusion criteria require participants to be at least 15 years old, with a weight between 30 kg and 150 kg, and a clinical diagnosis of severe EM. Exclusion criteria are not specified in the provided data.

The primary endpoint is the time to success, defined by controlled pain, resumption of food intake, and no need for rescue therapy. Secondary endpoints include the time to healing of all sites, fever resolution, length of hospital stay, and the rate of adverse events. Participants may be withdrawn from the study if they experience significant adverse effects or if they require rescue therapy, which involves intravenous methylprednisolone. The trial will utilize **prednisone** and a placebo, with the former being administered orally. The study aims to provide valuable insights into the management of severe EM, potentially improving patient outcomes and quality of life.

The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. **PREDNISONE ARROW 20 mg, comprimé sécable** is an experimental medication used in this study. It is presented in tablet form and contains the active substance **prednisone**. The medication is administered orally with a maximum daily dose of 1 mg/kg and a total maximum dose of 1800 mg over a treatment period of 12 days. The tablets are blinded in neutral blisters with specific labeling to maintain the integrity of the study. Participant compliance is monitored through regular assessments and adherence checks.

Another experimental treatment is **METHYLPREDNISOLONE**, which is administered intravenously. This medication contains the active substances **lidocaine hydrochloride monohydrate** and **methylprednisolone acetate**. The maximum daily dose is 0.8 mg/kg, with a total maximum dose of 1494 mg over a 12-day treatment period. The administration of this medication is carefully monitored to ensure accurate dosing and participant safety.

The study also includes a placebo comparator, **Placebo de prednisone ARW 20 mg**, which is composed of hydrogenophosphate de calcium dihydraté (94%), stéarate de magnésium (1%), and amidon de maïs Lycatab C (5%). This placebo is used to evaluate the efficacy of the experimental treatments by providing a control for comparison. The placebo is administered in a manner consistent with the experimental treatments to maintain blinding and study integrity.

Non-experimental treatments used in the study include **NaCl 0.9%** and **Glucose 5%**, which serve as standard-of-care therapies. These solutions are used as needed to support participant hydration and electrolyte balance during the trial. The administration of these solutions is conducted according to standard medical practice and is not blinded.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the time to success, defined by controlled pain with a Numeric Rating Scale (NRS) score of less than 4, sustained absence of the need for any level III analgesics for 48 hours, resumption of chopped or solid food intake, and no requirement for rescue therapy with intravenous **methylprednisolone** at 1 mg/kg/day. Secondary endpoints include the time to clear or almost clear healing of all sites, evaluated daily by clinicians, and the time to fever resolution, defined as the absence of fever (temperature ≤ 37.8°C) for at least 24 hours. Additional secondary endpoints involve the length of hospital stay, the number of days level III analgesics are consumed at least once per day, and the rate of patients requiring rescue therapy. Pain will be assessed three times daily during hospitalization and once daily post-hospitalization until the primary endpoint is achieved. The trial will also evaluate the rate of adverse events during treatment and follow-up, the rate of sequelae at 3 and 6 months, and the quality of life using the Patient Global Impression of Change (PGIC) scale at specified time points. These assessments will provide comprehensive data on the efficacy of the treatment regimen in the acute established phase of severe erythema multiforme.