NEWS: TNF inhibitors in uveitis

[Guest guest]

Sep 21, 2005



Zosia Chustecka

TNF inhibitors in uveitis

Liverpool, UK - The use of TNF inhibitors in the treatment of uveitis

is a controversial area, and the jury is still out regarding the

benefit and toxicity of the different products, comments an editorial

in the October 2005 issue of Rheumatology [1]. However, the evidence

so far suggests that there may be differential efficacy, with

infliximab (Remicade, Centocor/Schering-Plough) showing benefits, but

etanercept (Enbrel, Immunex/Wyeth) not, says Dr Bucknall (Royal

Liverpool University Hospital, UK).

This follows the pattern already seen with Crohn's disease, for which

infliximab is approved (in fact the US approval has just been

extended to cover ulcerative colitis), but etanercept shows no

benefit. The explanation may lie in the different mechanisms of

action of the two drugs, Bucknall suggests: infliximab induces cell

lysis after binding to TNF- and triggering the apoptosis of T

lymphocytes, whereas etanercept neutralizes lymphotoxin-. The

editorial does not mention the newest TNF inhibitor, adalimumab

(Humira, Abbott), and Bucknall tells rheumawire that there is very

little information on this product, but he would expect to see

similar efficacy to infliximab. His team is about to try it out in a

patient with retro-orbital Wegener's in remission with

cyclophosphamide with abnormal liver function.

In the editorial, Bucknall reviews some of the results with TNF

inhibitors that have been reported to date. In a trial of infliximab

in refractory uveitis, treatment success was reported for 22/28

patients at 10 weeks, 9/18 patients at one year, and 1/5 patients at

two years [2]. However, there was a high frequency of adverse events,

including three cases of drug-induced lupus, Bucknall comments.

Several published observations have suggested that etanercept,

despite its efficacy in treating arthritis, may actually induce

attacks of uveitis in patients who have not previously experienced

such episodes. In one of these—a retrospective study of 16 patients

with a variety of inflammatory eye and joint diseases [3]—there was

a universal benefit from TNF inhibition for the joint disease, but

only a 38% response rate for the associated uveitis or scleritis, and

in five patients the ocular inflammation began only after etanercept

was started. There is also a case report of a patient with ankylosing

spondylitis and bilateral anterior uveitis who had acute

exacerbations of uveitis that were temporally related to etanercept

injections [4]. A recent report involving both drugs and 18 patients

showed that 13/15 treated with infliximab had either complete or

partial control of ocular inflammation, whereas all seven patients

treated with etanercept failed therapy [5]. Five of these patients

were subsequently put on infliximab, and four achieved either a

complete or partial response.

Be aware of eye inflammation

Bucknall comments that the whole field of treating inflammatory eye

disease is at present somewhat controversial, but it is an area that

rheumatologists need to be aware of because of its association with

rheumatic disorders. " The rheumatologist ignores the association

between connective-tissue diseases and the eye at his or her peril, "

he says, adding that in the worst-case scenario the result may be

blindness.



The rheumatologist ignores the association between connective tissue

diseases and the eye at his or her peril.



One instance is peripheral ulcerative keratitis (PUK), also called

" corneal melt " , which can occur in patients with rheumatoid

arthritis. This is an aggressive destructive or necrotizing

ulceration of the peripheral cornea, presumed to be due to a

microangiopathic vasculitis, which can lead to rapid corneal melting

(keratolysis)—within the space of hours or days—and then to

perforation and eventual complete vision loss. " This is a rare

complication in RA and tends to occur in patients with systemic

disease, including Felty's syndrome, high titers of rheumatoid

factor, and low c4, " Bucknall tells rheumawire. Corneal melt can

occur spontaneously, he says, but his team has seen it in some

patients following routine cataract surgery, especially those

patients with the high-risk factors already mentioned. In these

cases, control of the disease before surgery is very important, he adds.

The treatment of choice for corneal melt would appear to be

cyclophosphamide given intravenously, on the basis that it probably

represents a form of vasculitis, Bucknall comments, referring to a

previous publication that he wrote with colleagues [6]. In this, a

letter to Rheumatology earlier this year, the group described

successful prophylaxis with intravenous cyclophosphamide in two

patients who had PUK in one eye before undergoing cataract surgery in

the other eye and say they have also had very good results with

intravenous cyclophosphamide in the treatment of spontaneous PUK.







Sources



Bucknall RC. Arthritis and inflammatory eye disease. Rheumatology

2005; 44:1207-1209. 

Suhler EB, JR, Pickard TD, et al A prospective trial of

infliximab therapy in patients with refractory uveitis. Trials,

tribulations, successes and setbacks. Invest Ophthalmol Vis Sci 2005;

46:e-abstract 2387.

JR, Levinson RD, Holland GN, et al Differential efficacy of

tumour necrosis factor inhibition in the management of inflammatory

eye disease and associated rheumatic disease. Arthritis Rheum 2001;

45:252-257. 

Taban M, Mandell B, VL. Etanercept associated inflammatory eye

disease case report and review of the literature. Invest Ophthalmol

Vis Sci 2005; 46:e-abstract 2849.

Lowder CY, Galor A, VL. Differential effectiveness of

etanercept and infliximab in ocular inflammation. Invest Ophthalmol

Vis Sci 2005; 46:e-abstract 2829. 

Clewes AR, Tunn EJ, Kaye S, Bucknall RC. Use of intravenous

cyclophosphamide in the prevention of corneal melt justified or not?

Rheumatology 2005; 44:257-258. 









http://www.jointandbone.org/viewArticle.do?primaryKey=565393