Rituximab Therapy in Patients With Treatment Refractory Hypersenstivity Pneumonitis

NCT ID: NCT07035561

Last Updated: 2025-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-01
• Study Completion Date: 2025-01-31

Brief Summary

Hypersensitivity pneumonitis (HP) presents with a highly variable clinical course, and Traditional treatment involves systemic corticosteroids in conjunction with strict avoidance of the offending antigen. However, a subset of patients with progressive disease remains unresponsive to conventional therapies. The objective of this study is to evaluate the therapeutic potential of Rituximab in individuals with refractory hypersensitivity pneumonitis who did not respond to conventional immunosuppressive therapy and antigen avoidance.

Assessing FVC at three intervals: six months prior to the initiation of Rituximab therapy (M-6), at the time of treatment initiation (M0), and six months afterward (M+6).

Detailed Description

The study will be conducted at the Chest Department, Faculty of Medicine, Cairo University during the period between June 2023 to January 2025. This study, which received approval from the Research Ethics Committee of Cairo University code (MD-180-2023), including 30 patients diagnosed with hypersensitivity pneumonitis at the Chest Department, Kasr Al Ainy Hospital, Cairo University.

Inclusion criteria:

1. Age 18 years old and above.

2. Patients with the diagnosis of chronic hypersensitivity pneumonitis, validated during a multidisciplinary team meeting with the criteria adapted from the CHEST guidelines 5, with decline in their FVC of greater than or equal 5% after a minimum of 6 months treatment including antigen avoidance and immunosuppressive therapy (including corticoseroids and Azathioprine).

Exclusion criteria:

1. Hypersensitivity to Rituximab.

2. Severe heart failure.

3. Moderate or severe pulmonary hypertension.

4. Fibrotic hypersensitivity pneumonitis.

5. Pregnancy.

6. Active infection.

Data collection: demographic data of all patients, smoking status, environmental or occupational exposure, onset and duration of symptoms, detailed history of previously received treatment, and oxygen therapy were collected. Assessment of Dyspnea grades using the modified Medical Research Council (mMRC) scale, full clinical examination including assessment of vital signs and chest auscultation were assessed. Routine laboratory investigations (CBC, Coagulation profile, Liver, Kidney functions, ABG) and Serum Immunoglobulins levels before and after initiation of therapy with Rituximab were obtained. All patients were screened for HBV, HCV and HIV infections by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc), Anti-HCV Antibodies, and Anti-HIV Antibodies. Also, all patients were screened for TB infection using QuantiFERON-TB Gold test. Fiberoptic bronchoscopy with BAL cellular analysis with/without TBLB (transbronchial lung biopsy) together with HRCT were performed to establish the diagnosis of HP and classify the patients into two groups (fibrotic and non-fibrotic). Spirometry and 6 min walk test (6 MWT) were performed to evaluate pulmonary function, Spirometry was performed for each patient three times during the study period, first time was 6 months before immunosuppressive therapy and antigen avoidance (M-6), Second time was at Rituximab administration (M0) and third time was 6 months after Rituximab administration (M+6). Echocardiography was performed to all patients to exclude moderate to severe pulmonary hypertension and heart failure. Prior to Rituximab administration patients were checked for active infection, their vital signs were checked including fever and clinical signs of infection were excluded prior to administration of Rituximab and their laboratory findings including CBC and serum CRP levels were checked to be within normal levels. Two doses of Rituximab were given, the first dose at day 0 and the second dose at day 15, 1 gram of Rituximab was given in each dose by an intravenous infusion. Patients were monitored for symptoms and signs of infections.

Statistical analysis: Data will be collected, tabulated, and statistically analyzed using an IBM compatible personal computer with Statistical Package for the Social Sciences (SPSS) version 26, quantitative data were presented in the form of mean, standard deviation (SD), median and range and qualitative data will be presented in the form numbers (N) and percentages (%), Chi-square test (χ2) or Fisher's Exact test were used to study association between two qualitative variables, Student's t test (t) was used for comparison of quantitative variables between two groups of normally distributed data, Mann-Whitney U test was used for comparison of quantitative variables between two groups of non-normally distributed data, Results will be considered statistically significant at a P value of less than 0.05.

Conditions

Hypersenstivity Pneumonitis; ILD

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab in treatment refractory Hypersenstivity pneumonitis

Patients diagnosed with chronic Hypersensitivity Pneumonitis who have not responded to standard treatment including antigen avoidance and immunosuppressive therapy.

Group Type: EXPERIMENTAL

Rituximab (Mabthera)

Intervention Type: DRUG

In Chronic hypersensitivity pneumonitis patients with no improvement in lung function (deterioration in their FVC% predicted more than or equal 5%) after a minimum of 6 months treatment including antigen avoidance and immunosuppressive therapy. Rituximab will be administered by an intravenous infusion.

• Two doses of Rituximab will be given, the first dose at day 0 and the second dose at day 15, 1 gram of Rituximab will be given in each dose.
• Patients will be given acetaminophen and antihistamine before each infusion.
• Rituximab will be diluted in an infusion bag of either 0.9% sodium chloride or 5% dextrose.
• No other drugs will be mixed with it, and patients will be closely monitored for any infusion reactions.

Interventions

Rituximab (Mabthera)

In Chronic hypersensitivity pneumonitis patients with no improvement in lung function (deterioration in their FVC% predicted more than or equal 5%) after a minimum of 6 months treatment including antigen avoidance and immunosuppressive therapy. Rituximab will be administered by an intravenous infusion.

• Two doses of Rituximab will be given, the first dose at day 0 and the second dose at day 15, 1 gram of Rituximab will be given in each dose.
• Patients will be given acetaminophen and antihistamine before each infusion.
• Rituximab will be diluted in an infusion bag of either 0.9% sodium chloride or 5% dextrose.
• No other drugs will be mixed with it, and patients will be closely monitored for any infusion reactions.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age 18 years old and above.

2. Patients with the diagnosis of chronic hypersensitivity pneumonitis, validated during a multidisciplinary team meeting with the criteria adapted from the CHEST guidelines, with decline in their FVC of greater than or equal 5% after a minimum of 6 months treatment including antigen avoidance and immunosuppressive therapy (including corticosteroids and Azathioprine).

Exclusion Criteria

1. Hypersensitivity to Rituximab.

2. Severe heart failure.

3. Moderate or severe pulmonary hypertension.

4. Fibrotic hypersensitivity pneumonitis.

5. Pregnancy.

6. Active infection.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shereen Medhat Mohammed Elsayed Nassar

OTHER

Sponsor Role: lead

Responsible Party

Shereen Medhat Mohammed Elsayed Nassar

Shereen Medhat Mohammed Elsayed Nassar was the principle investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Yosri M. Akl, Professor of Chest Diseases

Role: STUDY_CHAIR

Cairo University

Safy Z. Kaddah, Professor of Chest Diseases

Role: STUDY_DIRECTOR

Cairo University

Rana K Gabr, MD in Chest Diseases

Role: PRINCIPAL_INVESTIGATOR

Cairo University

Sherin M. Nassar, MSc in Chest Diseases

Role: PRINCIPAL_INVESTIGATOR

Cairo University

Locations

Kasr Al Ainy, Cairo University's Faculty of Medicine

Cairo, Cairo Governorate, Egypt

Countries

Egypt

References

Akl Y, Kaddah SZ, Nassar SM, El Said RK. Rituximab therapy in patients with treatment-refractory hypersensitivity pneumonitis. Sci Rep. 2025 Oct 17;15(1):36460. doi: 10.1038/s41598-025-21463-y.

Reference Type: DERIVED

PMID: 41107382 (View on PubMed)

Other Identifiers

MD-180-2023

Identifier Type: OTHER

Identifier Source: secondary_id

MD-180-2023

Identifier Type: -

Identifier Source: org_study_id