Document Detail

Non-infectious pulmonary toxicity of rituximab: a systematic review.
MedLine Citation:
PMID:  22157468     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Rituximab (RTX), a B-cell depleting mAb, has been reported to cause pulmonary toxicity in many patients. As the use of this biologic is increasing, we have undertaken a systematic review of the literature to gauge the nature and extent of non-infection-related RTX-induced lung disease.
METHODS: A systematic literature review was undertaken to document all reported cases of RTX-associated interstitial lung disease (RTX-ILD), evaluating the epidemiological, clinical, radiological, histopathological, laboratory and management data from the available primary sources. The search was conducted using PubMed, the Cochrane Library and EMBASE up to June 2010 using the terms RTX in the advanced search option without limitations and all relevant publications reviewed manually. In addition, unpublished data from the Food and Drug Administration, the European Medicines Agency and the manufacturer (Roche) were evaluated to complement this search. Identified articles were included if they displayed a potential relationship between the administration of RTX and ILD following exclusion of other likely causes.
RESULTS: A total of 121 cases of potential RTX-ILD were identified from 21 clinical studies/trials, 30 case reports and 10 case series. The most common indication for RTX was diffuse large B-cell lymphoma. RTX-ILD occurred more frequently in male patients and was most common during the fifth and sixth decades of life. In most cases, RTX was part of combination chemotherapy, but in 30 (24.7%) cases it was given as monotherapy. The mean and median number of cycles of RTX before disease onset was four, but cases following the first cycle or as late as the 12th cycle were also identified. The mean time of onset, from the last RTX infusion until symptom development or relevant abnormal radiological change was 30 days (range 0-158 days). Abnormal radiological findings were similar in all patients, with diffuse bilateral lung infiltrates apparent on chest radiographs and/or thoracic CT. Hypoxaemia was seen in all cases and pulmonary function tests were uniformly abnormal with a characteristic diffusion capacity deficit and restrictive ventilatory pattern. RTX-ILD was fatal in 18 cases.
CONCLUSION: ILD is a rare but potentially fatal complication of RTX therapy. This diagnosis should be considered in any patient who develops respiratory symptoms or new radiographic changes while receiving this biologic agent.
Andreas V Hadjinicolaou; Muhammad K Nisar; Helen Parfrey; Edwin R Chilvers; Andrew J K Ostör
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2011-12-07
Journal Detail:
Title:  Rheumatology (Oxford, England)     Volume:  51     ISSN:  1462-0332     ISO Abbreviation:  Rheumatology (Oxford)     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-19     Completed Date:  2012-05-08     Revised Date:  2013-01-02    
Medline Journal Info:
Nlm Unique ID:  100883501     Medline TA:  Rheumatology (Oxford)     Country:  England    
Other Details:
Languages:  eng     Pagination:  653-62     Citation Subset:  AIM; IM    
Rheumatology Research Unit, Box 194. Addenbrooke's Hospital, CUHNHSFT, Cambridge CB2 2QQ, UK.
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MeSH Terms
Antibodies, Monoclonal, Murine-Derived / administration & dosage,  adverse effects*
Antirheumatic Agents / administration & dosage,  adverse effects*
Drug Administration Schedule
Lung Diseases, Interstitial / chemically induced*,  diagnosis,  drug therapy
Time Factors
Grant Support
//Biotechnology and Biological Sciences Research Council; //Medical Research Council; //Wellcome Trust
Reg. No./Substance:
0/Antibodies, Monoclonal, Murine-Derived; 0/Antirheumatic Agents; 0/rituximab
Comment In:
Rheumatology (Oxford). 2012 Nov;51(11):2111-2; author reply 2112-3   [PMID:  22949728 ]

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