NEWS: Linking asthma and anti-TNF therapy

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Linking asthma and anti-TNF therapy



Oct 3, 2005



Gandey

London, UK - Could tumor-necrosis-factor (TNF)-blocking agents induce

asthma attacks? One group suggests this possibility, while

conflicting research explores the potential of these drugs in the

treatment of severe asthma. In a letter published in the September

2005 issue of Rheumatology, researchers report a case of adalimumab-

induced asthma [1]. The group says that this case is the only adverse

event of asthma with adalimumab (Humira, Abbott Laboratories)

reported to date by the UK-based Committee on Safety of Medicines,

but the committee has received other reports of asthma with

infliximab (Remicade, Schering-Plough/Centocor) and etanercept

(Enbrel, Wyeth/Amgen). The researchers say, " Asthma appears to be a

definite but rare side effect of anti-TNF blockade. "



In an interview with rheumawire, senior author Dr Bruce Kirkham

(Guy's Hospital, London, UK) said, " This is something clinicians

should be aware of, but I think it is fair to say that asthma is a

rare side effect. " One explanation the group suggests for this

adverse event is the contrasting inflammatory responses in rheumatoid

arthritis (RA) compared with asthma. In the case report of adalimumab-

induced asthma, the researchers hypothesize that the active RA

produced a T-helper cell (Th)1 cytokine response that suppressed the

clinical expression of asthma. But once the TNF inhibitor was

introduced, the Th1 response was suppressed, allowing the Th2-

activated pathway to express itself clinically as asthma. The

investigators report that this hypothesis suggests a class effect of

the TNF blockers.



Allergy and immunology specialist Dr Grayson (Washington

University, Saint Louis, MO) agrees with Kirkham that asthma is

likely a rare side effect of anti-TNF blockade. " At this point,

enough people have been treated with TNF blockers that I think it is

unlikely we will find more and more cases cropping up. "

Dr Lawrence Schwartz, chair of the division of rheumatology, allergy,

and immunology at the Virginia Commonwealth University in Richmond,

told rheumawire that he wonders whether the observed asthma

exacerbation was the result of reduced steroid doses. " Perhaps when

the patient went on the TNF blocker, steroid use such as prednisone

declined and that unveiled preexisting pulmonary disease. " Schwartz

says that although a cause and effect cannot be determined, it is an

issue that clinicians should keep in the back of their minds when

treating patients.

Could TNF blockers represent a new therapeutic target for severe asthma?

In another publication, researchers report the potential of TNF

blockade in the treatment of corticosteroid-dependent asthma [2]. The

small study in Thorax, published online September 15, 2005, shows

that TNF- production is higher in severe asthmatics. The group,

working under senior author Dr Holgate (Southampton General

Hospital, UK), studied 51 patients with severe asthma, 67 with mild

asthma, and 26 controls. They collected bronchial fluid and lung-

tissue samples and tested levels of TNF-.



Holgate and colleagues administered etanercept to 17 severe

asthmatics who still had symptoms despite being treated with a range

of drugs. Subjects received 25 mg injected twice weekly for 12 weeks.

" Etanercept treatment was associated with improvement in asthma

symptoms, lung function, and bronchial hyperresponsiveness, " the

group writes. " Since severe asthma makes up a substantial portion of

the health costs for this disease, we believe these novel

observations may be of clinical significance in identifying TNF- as

a new therapeutic target. "

Schwartz told rheumawire that he could see this as a possibility down

the road. But he cautions, " This would be for very select cases.

Severe asthmatics probably have a different pathology going on. "

Grayson said that he agrees: " I think this points to the fact that

asthma is probably not a single disease. " He adds that although TNF

blockers are showing promise in the treatment of corticosteroid-

dependent asthma, cost and ease of administration may present

barriers. " If we could drop the price to about $5 an injection, or

better yet, turn it into a pill, that would make a big difference. "







Sources



AN, Wong M, Zain A, et al. Adalimumab-induced asthma.

Rheumatology 2005; 44:1199-1200. 

Howarth PH, Babu KS, Arshad HS, et al. Tumour necrosis factor as a

novel therapeutic target in symptomatic corticosteroid-dependent

asthma. Thorax 2005; DOI:10.1136/thx.2005.045260. Available at:

http://thorax.bmjjournals.com. 

http://www.jointandbone.org/viewArticle.do?primaryKey=571337