Enbrel (etanercept), Remicade (infliximab) & Humira (adalimumab) comparison

[Guest guest]

Dr. Paget

Hospital for Special Surgery

on TNF and the TNF blockers from

" Rheumatoid Arthritis: A Patient's Reference (02/14/2003) " :

TNF

Tumor necrosis factor (TNF) blockers: TNF is a cytokine protein chemical

that plays a critical role in inflammation. All three of the available

TNF blockers have led to quantum clinical improvement over that obtained

with methotrexate alone. Infections, such as tuberculosis, and other

medical problems, such as low blood counts, have recently been reported.

Monitoring with blood counts and TB skin tests is appropriate and should

be guided by the physician. However, despite the necessity for caution

and increased monitoring, the benefits of these drugs continue to

outweigh their risks. You should discuss multiple issues, including

effectiveness, safety, how the drug is given and your likelihood of

using it as prescribed, as well as costs and your insurance coverage, as

the choice of a TNF blocker is being made.

ENBREL

Etanercept (Enbrel): This fusion protein combines two p75 TNF receptors

with an Fc receptor to form an immunoglobulin-looking molecule that

decoys the pro-inflammatory cytokine TNF. By doing so, it decreases the

binding of TNF to its cellular receptors and thus avoids the development

of tissue inflammation and damage. It is both highly effective and, to

date, safe. It not only leads to a clinical improvement over that

obtained with MTX alone, but it has been shown to be disease-modifying.

Infection risk is increased in those patients who have actively infected

skin ulcers or diabetes. No increased risk of tumors or autoimmune

disorders has been found. At this time, it is employed when patients

have not had an excellent response to full-dose MTX. Etanercept is

approved by the FDA for use with methotrexate, or may be used alone.

Dose: 25 mg by subcutaneous injection twice weekly. (This is similar to

the way people with diabetes give themselves shots for diabetes.) (See

our Special Report on Postmarketing Adverse Event Data on TNF-alpha

antagonists)

REMICADE

Infliximab (Remicade): This monoclonal molecule is composed of 3/4 human

and 1/4 mouse proteins. It is an antibody to TNF itself. Thus, it binds

TNF either in the blood or as it attaches to its receptor; by doing so,

it stops pro-inflammatory and tissue damaging actions. Infliximab leads

to both clinical improvement and a halting of erosion development and

joint space narrowing. At this time, infliximab is approved only for use

in combination with MTX. Rare cases of a lupus-like syndrome have been

reported; patients improved following discontinuation of therapy and

appropriate medical treatment. More than 80 cases of Mycobacterium

tuberculosis have been reported worldwide in patients who have been

treated with infliximab. The infection appears to occur soon after the

institution of infliximab, and some patients have developed disseminated

disease. Thus, a PPD (a test for TB) must be performed prior to starting

infliximab; if the test is positive, a chest X-ray should be done. If

the chest X-ray is normal, then infliximab can be used along with a

nine-month course of isoniazid and Vitamin B6 to prevent serious TB.

(See our Special Report on Postmarketing Adverse Event Data on TNF-alpha

antagonists) To date, the reported infection and tumor risk is not

greater in patients treated with infliximab than in RA patients not

treated with this medication. Caution in infliximab use in patients with

open skin ulcerations and/or diabetes would, however, be in order. Dose:

The usual starting dosing schedule is an infusion at weeks 0, 2, 6 and

then every 8 weeks. While the usual starting dose is 3 mg/kg in 250 cc

of saline over 2 hours, in those patients who have not responded

optimally this dose, it has been increased to 5 to10 mg/kg and the

frequency of infusions to monthly or every six weeks.

HUMIRA

Adalimumab (Humira): Adalimumab is the first fully human anti-TNF-alpha

monoclonal antibody. Therefore, it is less likely to spur your body to

produce new antibodies, and it may have greater therapeutic potential

than infliximab or etanercept. This is called " low immunogenicity " and

it may help avoid the need for taking methotrexate at the same time -

although using both drugs has been shown to yield efficacy benefits

beyond those that might simply be additive. The preliminary data

provided to the FDA suggest that adalimumab has an effectiveness and

safety profile similar to etanercept. It has been approved both for

reducing signs and symptoms of RA and inhibiting the progression of

structural damage in adults with moderately to severely active disease

who have had insufficient response to one or more DMARDs. As with the

other two TNF inhibitors, your doctor will observe precautions for

serious infections (including sepsis, tuberculosis, and fungal

infections), demyelinating disease, and malignancies (including

lymphoma), all of which also have been seen with adalimumab - although

rarely. Since rheumatoid arthritis itself has been associated with an

increased risk of lymphoma, the significance of the observed lymphoma

cases is as yet not determined. Dose: Adalimumab offers a much more

practical, patient-friendly dosing regimen than the other two TNF

blockers. You will give yourself one subcutaneous injection of 40 mg

every other week - again, similar to the way people with diabetes give

themselves shots.

http://rheumatology.hss.edu/pat/diseaseReviews/rheumArth/rheumArth_pat.asp

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org