Rituximab in Rheumatoid Arthritis Lung Disease
Condition: Rheumatoid Arthritis; Interstitial Pneumonia
MeSH terms: Pneumonia; Arthritis; Arthritis, Rheumatoid; Lung Diseases, Interstitial
Intervention: Rituximab
Intervention description: Rituximab 1000 mg. I.V.on each days 1 and 15 with repeat dosing at 6 months.
Intervention MeSH terms: Rituximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Rheumatoid Arthritis; Interstitial Pneumonia; Rheumatology; Rituximab

Summary:

      This study will examine the course of patients with progressive rheumatoid arthritis
      associated interstitial lung disease (RA-ILD) treated with rituximab for safety and
      progression-free survival at 48 weeks. Safety of rituximab therapy in this disease will be
      assessed through patient history, physical exams and laboratory parameters.

        -  Twelve male/or female patient with RA-associated lung disease (6 of each nonspecific
           interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP) histological
           subtype) will be enrolled

        -  The study involves 12 visits over 48 weeks

        -  Rituximab will be administered intravenously at Day 1 and Day 15 with repeat dosing at
           six months.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of RA according to the revised 1987 American Rheumatism Association criteria

          2. Absence of clinical features suggesting infection, neoplasm, sarcoidosis, interstitial
             lung disease other than UIP or NSIP, other collagen vascular disease, or exposure to
             known fibrogenic drugs or environmental factors

          3. Diagnosis of progressive interstitial pneumonia of UIP or NSIP subtype, based on the
             following criteria

               1. Clinical symptoms consistent with interstitial lung disease with onset between 3
                  months and 36 months prior to screening.

               2. Worsening as demonstrated by any one of the following within the past year:

                    -  > 10% decrease in Forced Vital Capacity (FVC)

                    -  increasing infiltrates on chest X-ray or High Resolution Computed Tomography
                       (HRCT), or worsening dyspnea at rest or on exertion

               3. Diagnosis of UIP or NSIP by either of the following:

                    -  Open or video-assisted thoracic surgery (VATS) lung biopsy showing definite
                       or probable UIP or NSIP

                    -  HRCT scan showing definite or probable UIP or NSIP AND abnormal pulmonary
                       function tests (reduced FVC or decreased diffusing capacity of carbon
                       monoxide (DLco) or impaired gas exchange at rest or with exercise) AND
                       insidious onset of otherwise unexplained dyspnea or exertion and bibasilar,
                       inspiratory crackles on auscultation

               4. FVC > 50% of predicted value at Screening

               5. DLco >30% of predicted value at Screening

        5. No change of disease-modifying anti-rheumatic drug (DMARD) treatment within the last 3
        months

        Exclusion Criteria:

          1. History of clinically significant environmental or drug exposure known to cause
             pulmonary fibrosis.

          2. Forced expiratory volume in one second (FEV1) FEV1/FVC ratio < 0.6 at screening (pre-
             or post-bronchodilator).

          3. Residual volume > 120% predicted at Screening

          4. Evidence of active infection

          5. Any pulmonary condition other than UIP/NSIP, which, in the opinion of the site
             principal investigator, is likely to result in the death of the patient within the
             next year

          6. History of unstable or deteriorating cardiac or neurologic disease

          7. Pregnancy or lactation

          8. Treatment with cyclophosphamide, cyclosporine, interferon gamma or beta, anti-tumor
             necrosis factor therapy, anti-interleukin 1 (IL1) therapy or with endothelin receptor
             blockers within the last 8 weeks; experimental therapy for rheumatoid arthritis

          9. Creatinine > 1.5 X upper limit of normal range (ULN) at Screening

         10. Hematology outside of specified limits: white blood cell (WBC) < 2,500/mm^3 or
             absolute neutrophil count (ANC) < 1500

         11. Hematocrit < 27% or > 59%, platelets < 100,000/mm^3 at screening

         12. Positive hepatitis B or C serology

         13. Any medical condition, which in the opinion of the site principal investigator, may be
             adversely affected by the participation in this study

         14. History of recurrent significant infection or history of recurrent bacterial
             infections

         15. Known active bacterial, viral fungal mycobacterial, or other infection (including
             tuberculosis or atypical mycobacterial disease, but excluding fungal infections of
             nail beds) or any major episode of infection requiring hospitalization or treatment
             with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks
             prior to screening

         16. Abnormal neurological examination reflective of central nervous disease, including
             paresis, cognitive impairment and problems with coordination

         17. Current enrollment in another clinical trial

         18. Fever (>99.5º F)

         19. History of previous rituximab administration

         20. Receipt of any vaccine, particularly live viral vaccines, within 4 weeks of first
             study dose

         21. Decreased Immunoglobulin G (IgG) and Immunoglobulin M (IgM) levels (below lower limit
             of normal range)

         22. Present or past malignancy

         23. History of severe allergic or anaphylactic reaction to administration of humanized or
             murine monoclonal antibodies

         24. Positive human immunodeficiency virus (HIV) serology