Comparison of Methylprednisolone or Methotrexate in the Maintenance Treatment of Nasal Polyposis

Methotrexate, as an anti-inflammatory drug used in animal experiments, and low dose systemic corticosteroid treatments have recently been suggested for the treatment of the CRwNP. Despite the several case reports of methotrexate being used for the severe and treatment-resistant CRwNP, the literature is a lack of clinical trials. Likewise, low-dose corticosteroid regimens have not been tested well contrary to the high dose corticosteroid therapy in the same course of the disease. Therefore, the main purpose of this study is to compare a low-dose of methylprednisolone or a low dose of methotrexate treatments with the standard intranasal, topical corticosteroid treatment in human volunteers with medical and surgical treatment-resistant CRwNP.

The present study was planned as a randomized, controlled, triple armed, parallel, open-label phase 2 clinical trial which is conducted in the Department of Otorhinolaryngology at Dokuz Eylül University Hospital. Human volunteers with CRwNP who are resistant to the medical and surgical therapies were recruited to the study. After randomization, the patients were divided into three groups including 14 volunteers in each study groups and 13 in the control group. One of the study groups was take methotrexate (n=14, eight weeks) and the other was take methylprednisolone (n=14, eight weeks). Each patient were evaluated by endoscopic examination, the nasal air-flow, the smell threshold, and the blood biochemistry both before and after the medications.

Efficacy goals of the study are located at below:

• Primary efficacy variable: Lund-Kennedy endoscopic grading system (NPS)
• Secondary efficacy variables: Total visual analog scale (VAS) score; the Turkish version of the Sinonasal Outcome Test-22 (SNOT-22); sum score of the peak nasal inspiratory flow (PNIF) and butanol olfactory threshold test (BuOT) obtained from bilateral nasal cavities; serum total immunoglobulin E (IgE) level; and the presence of peripheral eosinophilia (PE, > 500/mcl) in blood samples.

Safety goal of the study was evaluated by the examination of the adverse event reports and the number of patients who experienced adverse events.

Statistical analysis: The normality of the continuous variables was evaluated by the Shapiro Wilk test. Comparison of age was performed using one-way analysis of variance (ANOVA). Repeated measurements in three groups were analyzed using repeated measures ANOVA for 3×3 model with a within and a between-subjects factor. The results were assessed with a 95% confidence interval and at the p<0.05 significance level.

Inclusion criteria

• The diagnosis of chronic rhinosinusitis with nasal polyposis (CRS) with nasal polyposis which does not respond to maintenance treatment with topical nasal corticosteroid treatment after medical and surgical treatment,
• 18-75 years of age from both sexes,
• Signed an informed consent form,

Exclusion criteria

• Systemic oral methylprednisolone or systemic oral methotrexate treatment for another reason,
• Has a known malignant disease,
• Have contraindications or allergies to the use of excipients in oral methotrexate or preparations,
• Contraindications or allergies in the use of oral methylprednisolone or excipients contained in the preparation,
• Have contraindications or allergies to the use of excipients contained in nasal topical mometasone furoate or its preparation,
• Pregnancy status,
• Having a pregnancy plan,