TNF inhibitors set to revolutionize treatment of psoriasis

[Guest guest]

Rheumawire

Feb 12, 2004

TNF inhibitors set to revolutionize treatment of psoriasis

Washington, DC - Data reported at last week's American Academy of

Dermatology meeting in Washington, DC, show that the TNF inhibitors that

have been so successful in a variety of rheumatologic disorders are now

poised to revolutionize the treatment of psoriasis.

Dermatologist Dr Alice Gottlieb ( Wood Medical School, New

Brunswick, NJ) told rheumawire: " It's very exciting. TNF blockers change

lives and that's very gratifying. "

Three TNF inhibitors already on the market for rheumatoid arthritis are

currently in development for psoriasis. The furthest along is etanercept

(Enbrel®, Amgen/Wyeth), which is awaiting US approval for the treatment

of psoriasis; details of a large clinical trial outlining its efficacy

as monotherapy for this condition were published recently in the New

England Journal of Medicine [1,2]. The other 2 TNF inhibitors are

further back in development for this indication. Infliximab (Remicade®,

Centocor) is in phase 3 trials for psoriasis while adalimumab (HumiraTM,

Abbot Laboratories) is in phase 2.

Etanercept is already approved for use in psoriatic arthritis, and

Gottlieb explained that dermatologists have a key role to play in

managing these patients. " Skin disease often precludes joint disease by

around 10 years, so dermatologists will see these patients initially and

will be the first ones to pick up on their arthritis. "

For reasons that are not yet clear, psoriasis patients seem to need

higher doses of the TNF inhibitors to elicit responses than are needed

in arthritis. This is causing some concern that cost constraints may

limit use of these agents.

But last week at the dermatology meeting, a new phase 3 study of

etanercept in psoriasis showed that the disease could be successfully

controlled with only half the initial dose, once a three-month loading

dose had been given.

In this trial, 583 patients with moderate to severe psoriasis were

randomized to receive placebo, 25-mg etanercept twice weekly, or a

loading dose of 50-mg etanercept twice weekly for 12 weeks. For the next

12 weeks, those taking the loading dose of etanercept were " stepped

down " to half the dose (25 mg twice weekly), while patients taking 25 mg

twice weekly continued with the same dose. Patients initially taking

placebo were started on 25-mg etanercept twice weekly.

Half of the patients (49%) treated with the loading dose achieved the

primary end point, a 75% improvement in the Psoriasis Area Severity

Index (PASI75) in the first 12 weeks of the study, as compared with 34%

of patients taking 25 mg twice weekly and 3% of patients taking placebo.

A large majority (77%) of the patients treated with the loading dose who

had achieved a PASI75 response at week 12 maintained this response

through week 24 while receiving the stepped-down dose.

" This strategy worked for three quarters of the patients, but 25% still

needed the higher dose, " Gottlieb told rheumawire.

" It was very exciting to see that a large majority of these patients

maintained the effect while receiving half the loading dose, " said Dr

Craig Leonardi (Saint Louis University, St Louis, MO) in an Amgen press

release.

Another phase 3 study reported at the meeting showed that etanercept can

be successfully stopped and restarted in psoriasis patients for up to 3

months, where necessary. " It's not a good idea to stop therapy, " says

Gottlieb, " but in cases where you have to, such as pregnancy or surgery,

these data show that etanercept was stopped and restarted without severe

side effects due to psoriasis or loss of efficacy. "

Phase 2 results with infliximab and adalimumab were also reported at the

dermatology meeting, showing that both drugs were effective in the

treatment of psoriasis.

In a note commenting on the meeting, Merrill Lynch analysts described

the new data for infliximab in psoriasis as " highly encouraging " but

pointed out that there were 2 issues with this product that may affect

its take-up in the psoriasis market. First, it is given by infusion, and

many dermatologists are not equipped to provide infusion services; and

second, some patients will develop allergies to murine protein as a

result of using infliximab, which may present problems for the future

use of other therapies that contain murine proteins in these patients.

Gottlieb commented to rheumawire that this could be a problem because

" some of these patients will require rituximab in years to come. . . .

This issue has not been addressed well. "

Gottlieb stressed to rheumawire that a key difference between use of the

TNF inhibitors in arthritis and psoriasis is that in the psoriasis

trials TNF inhibitors are given solely as monotherapy and patients are

not continued on prednisone, methotrexate, or other agents, as often

happens in arthritis.

She also believes that lumping all the TNF inhibitors together under 1

umbrella is the wrong approach. " These TNF-targeting agents are not all

the same. " She has been involved in trials of both infliximab and

etanercept in psoriasis and says that, from her experience, so far she

believes etanercept to be the most encouraging agent. There is a good

safety database of etanercept in psoriasis patients now, she says, and

this shows so far that there is no increased risk of skin cancer with

the agent, a very important finding, she notes, because psoriasis

patients are at increased risk of skin tumors.

Nainggolan

Sources

1. Leonardi CL, Powers JL, Matheson RT, et al. Etanercept as monotherapy

in patients with psoriasis. N Engl J Med 2003 Nov 20; 349(21):2014-22.

2. Kupper TS. Immunologic targets in psoriasis. N Engl J Med 2003 Nov

20; 349(21):1987-90.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org