INFO - Enbrel (etanercept) versus Remicade (infliximab)

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Excerpt from s Hopkins Arthritis Center article on RA treatment:

Etanercept (Enbrel®)

Etanercept is effective in reducing the signs and symptoms of RA, as

well as in slowing or halting radiographic damage, when used either as

monotherapy or in combination with methotrexate. Etanercept is also

approved for the treatment of psoriatic arthritis and for ankylosing

spondylitis as well as psoriasis. Etanercept is a fusion protein that

combines two extracellular binding domains of the p75 form of the TNF

receptor with the Fc portion of a human IgG1 antibody molecule. The

components of the protein are entirely human, and anti-etanercept

antibodies are relatively uncommon.

Mechanism:

Etanercept binds TNF in the circulation and in the joint, preventing

interaction with cell surface TNF receptors thereby reducing TNF

activity.

Dosing:

The most common dose currently used is 50 mg self-administered once

per week by subcutaneous injection. Both prefilled syringes and an

autoinjection system (SureClick®) are available. Etanercept is also

available in a 25 mg dose which is administered twice per week at this

dose. Intermittent or occasional dosing has not been studied. There is

limited information on the safety or efficacy at doses beyond 50 mg

per week. Etanercept has a half-life of 70 hours after a 25mg dose.

Usual Time to Effect:

Etanercept has an onset of action of 1 to 4 weeks in improving signs

and symptoms with additional improvements that can be seen over 3-6

months.

Side Effects:

As with all TNF antagonists, there is an increased risk of infection.

In clinical trials, adverse there was not an overall difference

between the etanercept group and the placebo groups in rates of

serious infection, cancer, or death from any cause. There was an

increase in upper respiratory infection symptoms in etanercept treated

patients. Some patients develop positive antinuclear antibodies (ANA)

but cases of clinical lupus are reported but rare. Approximately 1% of

patients developed anti-etanercept antibodies but these were

non-neutralizing and did not affect the drug’s efficacy.

Post-marketing experience has indicated an enhanced risk for

infections including serious and opportunistic infections in patients

treated with etanercept and other TNF antagonists. Although

disseminated tuberculosis due to reactivation of latent disease has

been seen more commonly with infliximab and adalimumab than

etanercept, screening for latent TB is nonetheless prudent before

treatment with any TNF inhibitor. In some clinical trials of TNF

antagonists, lymphomas were more commonly observed in patients treated

with TNF inhibitors compared to placebo controls but the incidence

rates do not appear, at this time, to exceed those reported in the RA

population prior to the availability of TNF inhibitors. It is

important to note that RA itself is a risk factor for non-Hodgkins

lymphomas. Etanercept and other TNF inhibitors are not recommended in

patients with demyelinating disease or with congestive heart failure.

Transient neutropenia (lowering of white blood cell counts) or other

blood dyscrasias have been reported with etanercept and the other TNF

inhibitors.

Injection site reactions are sometimes seen with etanercept, but are

usually mild.

Infliximab(Remicade®)

Infliximab, in combination with methotrexate, is approved for the

treatment of RA, and for the treatment of psoriatic arthritis, and

ankylosing spondylitis, as well as psoriasis and Crohn’s disease.

Infliximab is a chimeric monoclonal antibody that binds TNF with high

affinity and specificity. The antibody binding site for TNF is of

mouse origin, with the remaining 75% of the infliximab antibody

derived from a human IgG1 antibody sequence.

Infliximab is effective as monotherapy in reducing the signs and

symptoms of RA but anti-infliximab antibodies can develop which can,

in turn, reduce the durability of the response. Co-treatment with

methotrexate reduces the frequency of these antibodies and is

therefore recommended along with infliximab. The combination of

infliximab and methotrexate is very effective in reducing clinical

manifestations of disease, as well as in slowing or halting

radiographic progression of disease in RA.

Mechanism:

Infliximab binds TNF in the joint and in the circulation, preventing

its interaction with TNF receptors on the surface of inflammatory

cells, and eventually clearing TNF from the circulation. Monoclonal

antibodies also bind to cell-bound TNF. Through its actions, nfliximab

inhibits the activity of TNF.

Dosing:

Infliximab is administered via the intravenous route. Infusions

typically take between 2-3 hours. The recommended starting dose of

infliximab is 3 mg/kg for RA given as an intravenous infusion followed

by additional dosing at 2 and 6 weeks, then every 8 weeks thereafter.

Infliximab should be given in combination with methotrexate. If the

clinical response is inadequate at a starting dose, infliximab can be

increased incrementally to a maximum dose of 10 mg/kg and the

frequency of infusion increased to every 4-6 weeks.

Usual Time to Effect:

Days to weeks.

Side Effects:

In clinical practice infections are increased in patients who receive

TNF antagonists, both mild and serious. In clinical trials, the

frequency of serious infections was not increased in infliximab +

methotrexate groups compared to methotrexate alone groups. A number of

cases of sepsis and disseminated tuberculosis and other opportunistic

infections have been reported for patients treated with TNF

antagonists. The risk for disseminated TB appears to be higher for

infliximab than etanercept, perhaps because of its longer half-life,

due to activities against cell bound TNF, due to lysis of target

cells, or because of more at-risk patients having been exposed to the

drug. However, all patients should be screened for latent TB before

initiation of any TNF inhibitor. All patients receiving a TNF

inhibitor should be carefully and continuously monitored for signs of

infection. Infliximab is not recommended in patients with congestive

heart failure or with demyelinating disease.

Patients receiving infused biological agents including infliximab may

develop a clinical syndrome of fever, chills, body aches, and headache

associated with the infusion of the antibody. In clinical trials of

infliximab, these symptoms were observed at relatively low frequency.

The symptoms can be reduced or prevented by slowing the infusion rate,

administration of diphenhydramine (Benadryl®), acetaminophen, and

sometimes corticosteroids before the infliximab infusion.

Anti-infliximab antibodies occur in 10-30% of patients depending on

the dosage and frequency of infusion but are suppressed by concomitant

methotrexate therapy. The development of ANA and anti-double stranded

DNA antibodies are seen with infliximab, and cases of clinical

SLE-like syndromes that may resolve upon drug discontinuation have

been reported.

http://www.hopkins-arthritis.org/arthritis-info/rheumatoid-arthritis/rheum_treat\

..html

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