title: Severe interstitial lung disease in connective tissue disease: rituximab as rescue therapy.
abstract: In very severe interstitial lung disease associated with connective tissue disease (CTD-ILD), progressing despite maximal conventional immunosuppression, there is no effective medical rescue therapy. The aim of the present study was to test whether rituximab, a monoclonal antibody that depletes peripheral B lymphocytes, is effective as rescue therapy in very severe CTD-ILD, unresponsive to conventional immunosuppression. We performed a retrospective assessment of eight patients with severe and progressive CTD-ILD treated with rituximab. In six patients, change in pulmonary function tests (PFTs) compared with pre-rituximab levels, was assessed at 9-12 months post-treatment. In two patients, who were mechanically ventilated at the time of treatment, clinical and HRCT changes were assessed. Seven out of eight patients had a favourable treatment response to rituximab, while in one patient disease severity did not change. In contrast with previous progression, we observed a median significant improvement of 22% in diffusing capacity for carbon monoxide (from a median baseline of 25%; range 16-32%; p=0.04), and a median significant improvement of 18% in forced vital capacity (from a median baseline of 45%; range 37-59%; p=0.03), in the 9-12 months following treatment with rituximab. In very severe CTD-ILD unresponsive to conventional immunosuppression, rituximab may represent an effective, potentially life-saving, therapeutic intervention.
authors.affiliation: Interstitial Lung Disease Unit, Royal Brompton Hospital, Sydney Street, SW3 6NP, London, UK. G.keir@rbht.nhs.uk
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Keir
authors.forename: Toby M
authors.initials: TM
authors.lastname: Maher
authors.forename: David M
authors.initials: DM
authors.lastname: Hansell
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Denton
authors.forename: Voon H
authors.initials: VH
authors.lastname: Ong
authors.forename: Suveer
authors.initials: S
authors.lastname: Singh
authors.forename: Athol U
authors.initials: AU
authors.lastname: Wells
authors.forename: Elisabetta A
authors.initials: EA
authors.lastname: Renzoni
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D002248:Carbon Monoxide / Q000032:analysis; D003240:Connective Tissue Diseases / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D017563:Lung Diseases, Interstitial / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D000069283:Rituximab; D012720:Severity of Illness Index
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007166:Immunosuppressive Agents; D000069283:Rituximab; D002248:Carbon Monoxide