Participating in a study where Remicade dose may be doubled!

[CrohnsKidMom]

We like to participate in studies where we can, for "the greater good" of all Crohnies, and we have recently been approached by my son's hospital inviting us to participate in a new study. The study is for 12-18 yr olds (my son is 12), and is to investigate if it is more beneficial to double a patient's Remicade dose, rather than shorten the length of time between infusions, in the event of a flare. I believe the standard dose is 5mg/kg, so should my son flare during the study (1 yr period), his infusions would stay at 8 week intervals, but his dose would increase to 10mg/kg. I have tried to find some information or studies that may have already been done on this theory, but haven't seen any in my limited search. Is anyone familiar with this topic? I'd like to help with the study, but I have some reservations. Doubling the Remicade dose does scare me.

 

[my little penguin]

Standard right now for Crohns is up to 10 mg/kg every 4 weeks
High experimental dose is 20 mg/kg every 4 weeks

So 10 mg/kg every 8 weeks isn't really that high in the grand scheme
When Ds was on remicade he took 7.5 mg/kg every 6 weeks

 

[my little penguin]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049116/

http://www.accessdata.fda.gov/drugsatfda_docs/label/2002/inflcen062802LB.pdf

http://www.crohnsforum.com/showthread.php?t=7617

Abstract

Background Patients treated with infliximab for Crohn's disease (CD) frequently require intensified dosage due to loss of response. There are scant data regarding the efficacy of shortening the dosing interval to 6 weeks.
Aim We sought to investigate the efficacy of a once every 6 weeks' strategy compared with dose-doubling.
Methods This work was a multicentre retrospective study of infliximab-treated CD patients who required dose escalation. The clinical outcome of patients treated by intensification to 5 mg/kg/6 weeks (6-week group) was compared with the outcome of patients whose infliximab was double-dosed (10 mg/kg/8 weeks or 5 mg/kg/4 weeks).
Results Ninety-four patients (mean age: 29.8 years) were included in the study, 55 (59%) in the 6-week group and 39 (41%) in the double-dose group. Demographics and disease characteristics were similar between the two groups, although patients with re-emerging symptoms 5–7 weeks postinfusion were more likely to receive 5 mg/kg/6 weeks dosing (OR: 3.4, 95% CI: 1.4–8.8, P < 0.01). Early response to dose-intensification occurred in 69% of patients in the 6-week group and 67% in the double-dose group (P = N.S.). Regained response was maintained for 12 months in 40% compared with 29% of the patients respectively (P = N.S.).
Conclusion In CD patients who lost response to standard infliximab dose, especially when symptoms re-emerge 5–7 weeks postinfusion, shortening the dosing interval to 6 weeks appears to be at least as effective as doubling the dose to 10 mg/kg or halving the infusion intervals to once in 4 weeks.

From

http://www.medscape.com/viewarticle/740069

 

[Tesscorm]

I think 10 mg/kg is not an unusually high dose. Over the years, I'm almost certain I've read of a number of kids here whose dosage is 10 mg/kg. My son is on 5 mg/kg but, in my mind, I've always thought that we 'easily' had room to move to 10 mg if it was necessary.

Have you looked through the Research subforum? Also, under the Parents subforum, there is another section for kids' research... I know I read one study/report which showed reducing length of time had been shown to be more beneficial, however, that was 'one' article and I don't recall how large a study it was done - so, one article/study isn't 'absolute'. FWIW, my son was moved to a 6 week interval but his dosage stayed the same.

I think what's more important is the serum level of his remicade just before the next dose. Will the study include running serum level tests (prometheus test)? When my son was started on remicade, he was given 5 mg/kg every 8 weeks. After the three loading doses, the day before his first 8 week infusion, his GI tested his serum levels. It was low, so he moved him to six weeks. Again, the morning of his first 6 week infusion, his GI ran the test again and levels were adequate. He's now been on remicade, at 5 mg every six weeks for a four years and his GI still runs the serum test every couple of years. I believe some studies (although his GI seems to feel this data is very limited) have shown optimal levels are at 5-8. My son's last test showed him at 12. But, when I asked GI if we could extend his cycle, his GI said he was happy with 12, that it gave a cushion if an infusion was delayed and that the 5-8 wasn't an absolute number. (Also said, he has a number of patients at levels in low 20s.)

One more thing... FWIW, when my son started on remi, he also registered in a remi study (it's been so long, I can't remember what exactly the study was analyzing nor if he's even still in the study) but, I do believe being in the study contributed to the serum level testing (ie, I recall the nurse mentioning the levels were being tested for the study but GI also got a copy of the results). He also had regular MRE/scope testing... again, not sure if the study required regular results and if that drove any of the testing 'schedule'?? In any case, I was grateful for the regular testing.

 

[my little penguin]

Background. Infliximab (INF) has been shown to be beneficial in treating refractory uveitis, however, no data exist on optimal dosing and the efficacy of higher dosing. Objectives. To compare the efficacy of low-dose (LD) (<10 mg/kg), moderate-dose (MD) (≥10–15 mg/kg), and high-dose (HD) INF (≥15–20 mg/kg) in the treatment of uveitis. Methods. Retrospective chart review children with uveitis diagnosed at Childrens Hospital Los Angeles and Millers Children’s Hospital, CA, USA. Results. Of the 34 INF-treated children, 6 patients received LD, 19 received MD, and 9 received HD. Average disease duration prior to therapy was 10.6, 24.6, and 37.1 months each group, respectively. Topical steroids were discontinued after an average of 3 months, 9.5 months, and 10.2 months in the LD, MD, and HD groups, respectively. We found that 66% of patients receiving LD, 42% of MD, and 66% receiving HD INF failed therapy and required either dose escalation or alternate medication for disease control. Conclusions. INF is beneficial in the treatment of uveitis, and dose escalation up to 4 times above the approved dose is often necessary to achieve disease control in patients with uveitis. Doses < 10 mg/kg every 4 weeks may not be sufficient to control disease.

From

https://www.hindawi.com/journals/isrn/2012/765380/




Clinical Study
High Dose Infliximab in the Treatment of Refractory Uveitis: Does Dose Matter?
Sukesh Sukumaran, Katherine Marzan, Bracha Shaham, and Andreas Reiff
Division of Pediatric Rheumatology, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA

Received 8 September 2011; Accepted 3 October 2011

Academic Editor: C. J. Chen

 

[pdx]

My daughter has been on 7 mg/kg every 6 weeks for the past 2 years, since 5 mg/kg every 8 weeks was never effective for her. She's been flaring since October, so we may go up to 10 mg/kg every 6 weeks soon. So to me, 10 mg/kg every 8 weeks doesn't seem overly high.

I think the question of whether it is more effective to reduce the interval or increase the dose is a very important one, so participating in the study does seem like a valuable public service. My only concern would be about my child ending up in the "wrong" half of the study. (That is, if reducing the interval turns out to be the better choice in your case.) I guess I would want to know what happens if your son continues to flare even after doubling his dose. Would they then be willing to also decrease the interval between doses?

 

[Maya142]

My daughter has been on 10 mg/kg every four week. No infections or side effects at all. I was very nervous but it was fine.
About a year after that, my daughter was put on an experimental high dose of Remicade. 20 mg/kg every 4 weeks. It was for her arthritis - her IBD was under control by then. I was terrified of infections and because there are some studies on the high dose Remi but not a whole lot.

Anyway, she was perfectly fine - no infections. I believe she was also on Sulfasalazine for part of the time and low dose MTX (7.5 mg) for some time with the high dose Remicade.

Good luck with whatever you decide!

 

[CrohnsKidMom]

Thank MLP, Tess, PDX, and Maya for your experiences, reassurances, and info!

Thanks for the articles, MLP. Exactly was I was looking for. Tess, I hadn't thought to check the Research section. Will do that, thanks. Currently, I believe my son's Remi levels are checked twice a year. If he joins the study, they will be checked prior to each infusion. I agree Tess, that's a plus. PDX, the interval of infusions would not change. All patients in the study group are currently at 8 weeks and would remain at such for the duration of the study. All members are at 5mg/kg as well. If my son does not flare, nothing changes for him. If he does flare his dose will double. There are also kids joining the study that are currently flaring (otherwise the study has the potential to be pointless!), and they are staying at 8 weeks and getting the 10mg/kg.

I guess I can relax over the double dose thing. That was my main concern. Things are going well for my son, he likes where he has his infusions done, likes the nurses, etc. If we join the study, infusions will be done in a different part of the hospital. I don't like rocking the boat when things are going well, but I like to be part of studies where I can. Decisions, decisions...

 

[Maya142]

I definitely understand not wanting to rock the boat. How does your son feel about doing infusions at another part of the hospital??

Do the kids get any sort of compensation for joining? My daughter just joined a CCFA study and for a stool sample, she got an Amazon gift card for $25 dollars (yes, that is some expensive poop )! She was thrilled because she doesn't usually get things from studies :lol:.

It sounds like a safe and well-planned study. As long as your son is willing, I'd go for it. The dose isn't unusually high and it's only if he flares (and chances are, if he did flare, they would change something anything - either the dose or the frequency).

I know the double dose sounds scary, but if it does happen, it's really not a big deal. It's just like getting the lower dose of Remi...the only thing we did definitely is bother my daughter to wash her hands more. We really had no issues, even on the absolute maximum dose.

My daughter was even given high dose IV steroids (1000 mg of IV Solumedrol for 3 days) with her first 20mg/kg infusion of Remicade and she still didn't get infections.

Good luck!!

 

[Clash]

C was older but at his highest dose he was on 15mg/kg every 5 weeks. Like I said he was older maybe 16 when he started. At the time he was probably 100 lbs.

 

[christine richter]

Our 21 year old son had a bad flare last year, and was put on the double dose of 20mg every 6 weeks. He is feeling better, with a small opening in his strictures. No side effects so far.