The article, "Optimizing Anti-TNF Therapy" by Jason W. Harper and Scott D. Lee is found on pages 687-692 of the book, "Advanced Therapy in Inflammatory Bowel Disease" and is supported by 14 references. For any of you interested in the deeper medical side of Crohn's Disease, this book is fantastic but be warned, it is aimed at medical practitioners and is heavy reading. This thread will contain information I feel is useful in the article and I also open it up for discussion.
- In regards to inducing remission, there is no data to suggest any of the three available anti-TNF medications: infliximab (Remicade), adalimumab (Humira) or certolizumab pegol (Cimzia) are statistically superior. As such, the choice of medication is based more on how convenient the dosing mechanism is, cost to patients, and clinical experience.
- Age, sex, duration of disease, severity, surgeries, location of disease, family history, blood markers, and smoking do not appear to have any affect on whether anti-tnf medications induce remission or not.
- Usage of other biologics previously and use of other medications do not appear to affect whether anti-tnf medications work or not.
- Abscesses and strictures due to scarring won't respond to anti-tnf medications so it's important to rule out their presence.
- Anti-tnf medications appear to be the most effective maintenance meds.
- Regular scheduled therapy is far superior to episodic dosing.
- LONG TERM response to anti-tnf does have some variables that matter. These are: duration of disease, previous use of anti-tnf medications, antibodies to the medication, episodic therapy, and other use of medications at the same time.
- If a patient has had Crohn's disease for a shorter duration, there is a better chance of a long term response to anti-tnf medications, possibly due to the prevention of irreversible damage such as strictures and abscesses.
- Patients who were diagnosed within 2 years of starting anti-tnf medication have the best chance of maintaining remission.
- In studies of Humira and Cimzia, they found that if you had failed infliximab previously, you had a lower chance of maintaining remission than someone who hadn't had an anti-tnf medication previously. They don't know why but it doesn't seem to be related to antibodies.
- Around 40-50% of people eventually no longer respond to biologics, usually due to the formation of antibodies.
- All anti-tnf medications have antibodies formed against them.
- As of this article writing, only antibody tests were available for Remicade.
- If someone doesn't have antibodies to Remicade but has low levels of the medication in their system, they'll up the dose or shorten the interval. If they patient doesn't have antibodies but is not responding despite having therapeutic levels of the medication in their system, they'll switch to a different type of medication. If they have antibodies they'll switch them to another anti-tnf.
- Episodic treatment rather than regularly scheduled dosing is shown to lead to antibody formation. As in 60% versus around 8-12% for regularly dosed patients.
- When azathioprine and Remicade are taken together, it results in higher amounts of Remicade in the blood than when Remicade is taken alone.
- Methotrexate at doses as low as 7.5mg per week is shown to reduce antibody formation and hasn't shown a significant increase in cancer or infection rates.
- Remicade and 25mg subcutaneously of methotrexate did not increase maintenance of remission at the one year mark versus Remicade alone.
- The SONIC trial showcased that Remicade and Azathioprine together increased rates of maintaining remission of the patient hadn't taken either before.
- The author recommends combination therapy of Remicade and Azathioprine if the patient hasn't been on either previously due to the increased response rates. This is especially true of the patient has perianal disease, multiple surgeries, loss of response to a previous biologic, a history of not taking infusions regularly resulting in episodic treatment, incomplete response to anti-TNF meds.
- The author tries to avoid combination therapy with methotrexate in women if they are of child bearing potential and combination with azathioprine in men under 30 to avoid hepatospleno T-cell lymphoma.
- If a patient is on the combination therapy and gets an infection, they drop the immunosuppressant.
- If the patient is in remission at 12 months they'll consider stopping the immunosuppressant but monitor the patient very closely.
- If response is lost, either increasing the dose or shortening the dosing interval recaptures response in the majority of patients.
- If the dose is increased, after 6-12 months the authors try to reduce the dose back down to the original dose. If the response is lost again, they'll go back up and maintain at the higher dose indefinitely.
- With Humira, if response is lost, they increase the dose from 40mg every two weeks to 40mg every week. After six months if the patient recaptures response, they try to take the dose back to once every two weeks.
- A study, not yet published at the time of the book printing, showcases that 50% of patients who were doing well on Remicade but switched to Humira for convenience reasons flared.
