Rituximab Versus Cyclophosphamide in Connective Tissue Disease-ILD

Inclusion Criteria: * Age 18 to 80 years at visit 1 * A diagnosis of connective tissue disease, based on internationally accepted criteria, in one of the following categories21-24: (see Appendix 1 for details) * Systemic sclerosis * Idiopathic interstitial myopathy (including polymyositis/dermatomyositis) * Mixed connective tissue disease * Severe and/or progressive interstitial lung disease associated with the underlying connective tissue disease. * Chest HRCT performed within 12 months of study visit 1 * Intention of the caring physician to treat the ILD with intravenous cyclophosphamide (with treatment indications including deteriorating symptoms attributable to ILD, deteriorating lung function tests, worsening gas exchange or extent of ILD at first presentation) and where there is a reasonable expectation that immunosuppressive treatment with stabilize or improve CTD-ILD. In individuals with scleroderma it is anticipated that subjects will fulfil the criteria for extensive disease defined by Goh et al19 * Able to provide written informed consent Exclusion Criteria: * Age \<18 or \>80 years. * Previous treatment with rituximab and/or intravenous cyclophosphamide * Known hypersensitivity to rituximab or cyclophosphamide or their components * Significant (in the opinion of the investigator) other organ co-morbidity including cardiac, hepatic or renal impairment * Co-existent obstructive pulmonary disease (e.g. asthma, COPD, emphysema) with pre bronchodilator FEV1/FVC \< 70% * Patients at significant risk for infectious complications following immunosuppression, including; HIV positive or other immunodeficiency syndromes (including hypogammaglobulineamia) * Suspected or proven untreated tuberculosis * Viral hepatitis * Infection requiring antibiotic treatment in the preceding four weeks * Unexplained neurological symptoms (which may be suggestive of progressive mutifocal leukoencephalopathy; PML). Neurological symptoms arising as a consequence of the underlying CTD do not necessitate exclusion. * Other investigational therapy (participation in research trial) received within 8 weeks of visit 1 * Immunosuppressive therapy (other than corticosteroids) received within 2 weeks of visit 1 (randomization) * Pregnant or breast feeding women, or women of child-bearing potential, not using a reliable contraceptive method * Unexplained haematuria, or previous bladder carcinoma * Unable to provide informed written consent