David
Co-Founder
The article, "Switching Anti-TNF Agents: Evidence-Based Results and Clinical Experience" by Remo Panaccione is found on pages 683-686 of the book, "Advanced Therapy in Inflammatory Bowel Disease" and is supported by 22 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.
- The reasons for switching anti-tnf might include: primary non-response when first starting the medication, loss of response after some duration, intolerance to a medication, or interruption of doses.
- When you switch from one anti-tnf to another, there is no need for a delay between doses to let the other medication exit your system and you should get a full induction dose.
- Some people want to switch from infliximab (Remicade) to adalimumab (Humira) or certolizumab pegol (Cimzia) because they allow for self-injecting even when they're having a good response to Remicade. While there is no data on this, it is not advised. The primary reason is they feel if you lose response to the new medication, there's a good chance you'll lose response to the old medication as well due to immunogenicity (you develop antibodies to it). So you'd lose out on two medications. It is also not advised to switch from Humira or Cimzia to Remicade for the same reasons.
- One third of patients will not respond to anti-tnf therapy.
- If you don't respond to a biologic, you are a "Primary nonresponder".
- If you don't appear to be responding to a biologic, it's important that your physician make sure it's not due to something else such as, strictures, fistulae, abscesses, c.diff, small intestine bacterial overgrown (SIBO), CMV, bile salt diarrhea, etc.
- You should have your full induction dosing before being termed a primary nonresponder.
- For Remicade, some suggest the full induction dose then, at the 6 week dose, double the dose before determining non-response.
- For Humira, it is suggested to wait a full 12 weeks before determining non-response.
- Sometimes people with Crohn's don't respond well to anti-tnf because that's not the primary component of their inflammatory response. In that is suspected as the reason for a primary non-response, trying natalizumab (Tysabri) may be worthwhile as it isn't an tnf blocker and has shown efficacy when people fail anti-tnf therapy. It does increase the risk of progressive multifocal leukoencephalopathy (PML) so that risk needs to be weighed.
- Of those who initially respond to anti-tnf medications, 40-50% will stop responding within 12 months
- Thereafter, data shows that 10-15% will lose response on a year by year basis.
- When you experience a secondary loss of response, you can increase the dose, shorten the interval between doses, switch to another anti-tnf, or switch to another type of medication.
- Just as with primary nonresponders, it is important that your doctor make sure that you're not experiencing symptoms that are not actually indicative of loss of response.
- At the time of the article, only antibodies to Remicade could be tested for. I'm curious of they have tests for Humira and Cimzia yet.
- If someone appears to be losing response, making sure that inflammation is back via CRP, ESR, increased platelets, fecal calprotectin is important so as to rule out other causes such as infection.
- The author suggests someone who appears to stop responding should be evaluated via colonoscopy, capsule endoscopy, CTE, or MRE as well.
- A study out of the Mayo Clinic found that about 50% of people with symptoms of a flare were not actually inflamed and it was coming from some other cause.
- For people on Remicade who start to lose response and are negative on antibodies but have no or no detectable serum levels of the medication, increasing the dose or shortening the interval may work well.
- If someone is on Remicade and get symptoms not long after an infusion, then a dose increase is probably the best bet. If they do well until just before the next infusion, then shortening the interval would likely be best.
- Increasing the dose has been shown to help about 80% of people who start to lose response.
- For Humira, increases the dose from 40mg every other week to 40mg every week helps about 50% of people.
- In Cimzia, the dose changes from 400mg every 4 weeks to 400mg every 2 weeks.
- If you are found to have antibodies to Remicade but were initially a responder, then switching to another anti-tnf is likely the best bet.
- One study (GAIN) showed switching from Remicade to Humira was better than placebo and one study (WELCOME) found the same for switching from Cimzia to Remicade.
- If someone has a reaction to infusions, often the best option is to treat that reaction. Minor reactions such as rash, flushing, minor chest pain, or dyspnea (shortness of breath) can be treated beforehand with steroids, antihistamines, or tylenol depending on the reaction at the previous infusion.
- If someone has reactions to Remicade, it's important to test for antibodies as those type of reactions tend to get worse over time.
- Changes in vital signs, severe chest pain, and anaphylactoid reactions warrant changing medications to a different anti-tnf.
- Many people get skin problems such as folliculitis, pseudopsoriasis, palmar-plantar pustulosis, or psoriasis. These usually don't warrant switching to a new medication and a dermatologist can help control them.
- Arthritis, arthralgia, lupus-like syndrome, and drug induced lupus are relative common with anti-tnf medications. Many in fact develop antinuclear antibodies and anti- double stranded DNA antibodies. It is not felt that this is cause to switch to another medication but a rheumatologist should be consulted. If someone develops drug induced lupus, then a switch should be made. It is felt the chance of drug induced lupus with Cimzia is much less so a switch to it is logical.
- Sometimes people will have surgery which interrupts the dosing of the biologic. Any dose interruption may cause development of antibodies. The suggestion is to go back on the original medication if they were responding well to it. If possible, first measure for antibodies.
Good article.
- The reasons for switching anti-tnf might include: primary non-response when first starting the medication, loss of response after some duration, intolerance to a medication, or interruption of doses.
- When you switch from one anti-tnf to another, there is no need for a delay between doses to let the other medication exit your system and you should get a full induction dose.
- Some people want to switch from infliximab (Remicade) to adalimumab (Humira) or certolizumab pegol (Cimzia) because they allow for self-injecting even when they're having a good response to Remicade. While there is no data on this, it is not advised. The primary reason is they feel if you lose response to the new medication, there's a good chance you'll lose response to the old medication as well due to immunogenicity (you develop antibodies to it). So you'd lose out on two medications. It is also not advised to switch from Humira or Cimzia to Remicade for the same reasons.
- One third of patients will not respond to anti-tnf therapy.
- If you don't respond to a biologic, you are a "Primary nonresponder".
- If you don't appear to be responding to a biologic, it's important that your physician make sure it's not due to something else such as, strictures, fistulae, abscesses, c.diff, small intestine bacterial overgrown (SIBO), CMV, bile salt diarrhea, etc.
- You should have your full induction dosing before being termed a primary nonresponder.
- For Remicade, some suggest the full induction dose then, at the 6 week dose, double the dose before determining non-response.
- For Humira, it is suggested to wait a full 12 weeks before determining non-response.
- Sometimes people with Crohn's don't respond well to anti-tnf because that's not the primary component of their inflammatory response. In that is suspected as the reason for a primary non-response, trying natalizumab (Tysabri) may be worthwhile as it isn't an tnf blocker and has shown efficacy when people fail anti-tnf therapy. It does increase the risk of progressive multifocal leukoencephalopathy (PML) so that risk needs to be weighed.
- Of those who initially respond to anti-tnf medications, 40-50% will stop responding within 12 months
- Thereafter, data shows that 10-15% will lose response on a year by year basis.
- When you experience a secondary loss of response, you can increase the dose, shorten the interval between doses, switch to another anti-tnf, or switch to another type of medication.
- Just as with primary nonresponders, it is important that your doctor make sure that you're not experiencing symptoms that are not actually indicative of loss of response.
- At the time of the article, only antibodies to Remicade could be tested for. I'm curious of they have tests for Humira and Cimzia yet.
- If someone appears to be losing response, making sure that inflammation is back via CRP, ESR, increased platelets, fecal calprotectin is important so as to rule out other causes such as infection.
- The author suggests someone who appears to stop responding should be evaluated via colonoscopy, capsule endoscopy, CTE, or MRE as well.
- A study out of the Mayo Clinic found that about 50% of people with symptoms of a flare were not actually inflamed and it was coming from some other cause.
- For people on Remicade who start to lose response and are negative on antibodies but have no or no detectable serum levels of the medication, increasing the dose or shortening the interval may work well.
- If someone is on Remicade and get symptoms not long after an infusion, then a dose increase is probably the best bet. If they do well until just before the next infusion, then shortening the interval would likely be best.
- Increasing the dose has been shown to help about 80% of people who start to lose response.
- For Humira, increases the dose from 40mg every other week to 40mg every week helps about 50% of people.
- In Cimzia, the dose changes from 400mg every 4 weeks to 400mg every 2 weeks.
- If you are found to have antibodies to Remicade but were initially a responder, then switching to another anti-tnf is likely the best bet.
- One study (GAIN) showed switching from Remicade to Humira was better than placebo and one study (WELCOME) found the same for switching from Cimzia to Remicade.
- If someone has a reaction to infusions, often the best option is to treat that reaction. Minor reactions such as rash, flushing, minor chest pain, or dyspnea (shortness of breath) can be treated beforehand with steroids, antihistamines, or tylenol depending on the reaction at the previous infusion.
- If someone has reactions to Remicade, it's important to test for antibodies as those type of reactions tend to get worse over time.
- Changes in vital signs, severe chest pain, and anaphylactoid reactions warrant changing medications to a different anti-tnf.
- Many people get skin problems such as folliculitis, pseudopsoriasis, palmar-plantar pustulosis, or psoriasis. These usually don't warrant switching to a new medication and a dermatologist can help control them.
- Arthritis, arthralgia, lupus-like syndrome, and drug induced lupus are relative common with anti-tnf medications. Many in fact develop antinuclear antibodies and anti- double stranded DNA antibodies. It is not felt that this is cause to switch to another medication but a rheumatologist should be consulted. If someone develops drug induced lupus, then a switch should be made. It is felt the chance of drug induced lupus with Cimzia is much less so a switch to it is logical.
- Sometimes people will have surgery which interrupts the dosing of the biologic. Any dose interruption may cause development of antibodies. The suggestion is to go back on the original medication if they were responding well to it. If possible, first measure for antibodies.
Good article.
