Rheumatology Advance Access originally published online on December 10, 2006
Rheumatology 2007 46(2):372-373; doi:10.1093/rheumatology/kel374
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reply to comment on ‘Drug-related pulmonary problems in patients with rheumatoid arthritis’ by Yazici and Yazici and ‘Pulmonary adverse events with Leflunomide—myth or reality?’ by Balakrishnan and Dasgupta
Department Medicine and Rheumatology, Queen Elizabeth Hospitals NHS Trust, Sheriff Hill, Gateshead NE9 6SX, UK.
Correspondence to: C. A. Kelly, Consultant Physician and Rheumatologist, Department of Medicine and Rheumatology, Queen Elizabeth Hospitals NHS Trust, Sheriff Hill, Gateshead NE9 6SX, UK. E-mail: clive.kelly{at}ghnt.nhs.uk
SIR, Dr Yacizi and Dr Yacizi express two concerns relating to the incidence of methotrexate pneumonitis as stated in our earlier editorial [1], and we will deal with each in turn.
The first concern relates to the wide variation in reported frequency of pneumonitis in patients on methotrexate, and clarification on referenced sources was requested. Given the limited number of references allowed in an editorial, we were obliged to simplify our sources. However, in a previous ‘viewpoint’ article for Rheumatology [2] we dealt with this subject in considerable detail. We agree that careful analysis of the data in the article by Groves et al. [3] suggests a low incidence (0.5%) of methotrexate pneumonitis overall, with all reported cases occurring in the first year. However, there is considerable variation in the literature with much higher frequencies reported in smaller prospective studies (6.9%) [4] and in primary biliary cirrhosis (14%) [5].
Secondly, we agree with their explanation that using patient-years as denominators for events such as methotrexate pneumonitis will bias the results towards under-reporting. However, using the proportion of patients stopping methotrexate or any other drug after an acute respiratory illness may over-estimate this risk unless the cases of pneumonitis have been carefully ascertained. We found in our practice that perceived respiratory toxicity and actual occurrence of acute respiratory events of all causes were high compared with the real incidence of pneumonitis [6]. A similar situation may apply with leflunomide as Balakrishnan and Dasgupta's reports of substantial pulmonary adverse events associated with this drug showed only one of three deaths was due to new interstitial lung disease.
The true frequency with which methotrexate (and leflunomide) precipitate pneumonitis in the first and each subsequent year of therapy could be quantified if the data from all reported studies were amalgamated and reanalysed. We disagree with the Yazici and Yazici's statement that ‘apart from the relatively few patients with these early adverse effects the remaining patients who are prescribed the drug (methotrexate) will never get these reactions however long they use the drug’. Several reports exist of patients developing pneumonitis after more than 12 months on methotrexate and anti-TNF biological drugs have also been reported to cause acute inflammatory respiratory illness in patients, most of whom have also been on methotrexate for over a year [7]. Do we blame the anti-TNF drugs, methotrexate or hitherto undiagnosed pulmonary fibrosis related to RA?
Perhaps we should move away from the concept that drug-related pneumonitis or worsening of pre-existing pulmonary fibrosis is purely due to the drug. These inflammatory reactions may occur due to a change in the inflammatory milieu of the underlying auto-immune disease, and are rarely seen in patients receiving similar doses of the same drug for conditions with a different aetiopathogenesis, e.g. psoriatic arthritis.
The authors have declared no conflicts of interest.
 |
References |
|---|
 Top References |
|---|
- Saravanan V and Kelly C. (2006) Drug-related pulmonary problems in patients with rheumatoid arthritis. Rheumatology 45:787–9.
[Free Full Text] - Saravanan V and Kelly CA. (2004) Reducing the risk of methotrexate pneumonitis in rheumatoid arthritis. Rheumatology 43:143–7.
[Free Full Text] - Grove ML, Hassell AB, Hay EM, Shadforth MF. (2001) Adverse reactions to disease-modifying anti-rheumatic drugs in clinical practice. Q J Med 94:309–19.[Web of Science]
- Kremer JM and Phelps CT. (1992) Long-term prospective study of the use of methotrexate in the treatment of rheumatoid arthritis. Update after a mean of 90 months. Arthritis Rheum 35:138–45.[Web of Science][Medline]
- Sharma A, Provenzale D, McKusick A, Kaplan MM. (1994) Interstitial pneumonitis after low-dose methotrexate therapy in primary biliary cirrhosis. Gastroenterology 107:266–70.[Web of Science][Medline]
- Chu CHI, Sajid A, Thompson B, Saravanan V, Kelly CA. (2006) Investigating acute respiratory events with methotrexate therapy. Rheumatology 45:i40 Abstract no. 83.
[Free Full Text] - Kramer N, Chuzhin Y, Kaufman LD, Ritter JM, Rosenstein ED. (2002) Methotrexate pneumonitis after initiation of Infliximab therapy for rheumatoid arthritis. Arthritis Rheum (Arthritis Care & Research) 47:670–71.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||