need help figuring out a study, please | Arthritis Information
Calling all the smarty pants! I'm 'dissecting' a study.
I've got one, done by doctors who had no conflicts of interest to disclose, that concludes, "The majority of patients tolerated anti-TNF therapy with no difficulty. Although the rates of important adverse events were low, there were serious events reported from our centre including significant infusion reactions necessitating discontinuation of the biologic agent. The balance of risks and benefits of any anti-TNF agent should be carefully considered prior to use for the treatment of children with rheumatic disease."
That's what I'm talkin' about.
So I've got another one, done by doctors with lots to disclose, about Enbrel. It concludes, "Safety data from this ongoing registry support the use of etanercept in this patient population for up to 3 years."
Does anyone know the answer to this? The study uses percentages to describe remission, discontinuation, total joint count = 0, and physican global assessment = 0. But serious adverse events and medically important infections (hello? the 'safety' part) are listed as "per 100 pt-yrs".
As a parent, what I want to know from this study is the percentage of children who had SAEs and MIIs.
So, does anybody know if that is possble? Or why it is presented differently?
The first abstract:
Suzanne2008-03-24 06:50:54The second abstract:
Typically all the results are stated in the abstract. The study itself is just the delination of what they did and how they went about it. I will read the study and get back with you. I used to read studies all the time and have to write papers on them.
the long-term safety of anti-TNF therapy in children is not known.
Conclusion: The majority of patients tolerated anti-TNF therapy with no difficulty. Although the rates of important adverse events were low, there were serious events reported from our centre including significant infusion reactions necessitating discontinuation of the biologic agent. The balance of risks and benefits of any anti-TNF agent should be carefully considered prior to use for the treatment of children with rheumatic diseases.
This is from the abstract of the first study...the population studied was only 182, not a huge sample.
of these:
severe infection requiring hospitalization 1.1 % (2),
seroconversion for TB 0.55% (1),
severe infection requiring treatment with no hospitalization 1.6% (3)
autoantibody formation 1.6% (3)
severe headaches with abnormal MRI 1.1% (2),
and hyperreflexia 0.55% (1).
Of the infliximab infusion patients, 5.9% (6) had a severe infusion reaction leading to discontinuation of biologic agent despite all receiving pre-infusion protocol administration of acetaminophen and diphenhydramine.
I would allow the treatment on my child.
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601 patients enrolled;
198 received MTX,
105 received ETN,
298 received MTX/ETN.
131 MTX patients (66%),
51 ETN patients (49%),
146 MTX/ETN (49%) patients discontinued the registry.
In the MTX, ETN, and MTX/ETN groups respectively, 24 (12%),
7 (7%),
11 (4%)
patients discontinued because of remission,
35 (18%)
7 (7%),
51 (17%)
discontinued because of an insufficient therapeutic effect
3 (1.5%)
2 (1.9%)
1 (0.3%)
discontinued because of adverse events.
159 patients (26%) have completed the 3-years registry to date.
The rates of serious adverse events and medically important infections per 100 pt
-yrs were 5.25, 8.36, and 5.78, and 0.95, 1.97, and 1.98 respectively, for patients receiving MTX, ETN, or MTX/ETN.
One case of lupus (MTX) and 2 cases of sepsis (ETN and MTX/ETN) were reported.
No cases of lymphoma, malignancy, tuberculosis, or death were reported.
The median ( average)number of active joints reported was decreased at 24 months as compared to baseline for all groups
(MTX, 6 to 0; ETN, 4 to 0; MTX/ETN, 6 to 1), as were median PhGA scores (MTX, 4 to 1; ETN, 3 to 1; MTX/ETN, 4 to 1).
Also, the percentage of patients reporting total joint counts = 0 was increased at 24 months vs baseline in all groups (MTX, 12% to 56%; ETN, 18% to 53%; MTX/ETN, 12% to 40%) ( got better)as were the percentage of patients with total PhGA = 0 (MTX, 7% to 43%; ETN, 7% to 34%; MTX/ETN, 6% to 32%).
Conclusion: Safety data from this ongoing registry support the use of etanercept in this patient population for up to 3 years.
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Hope I helpedUnfortunately, there are no large studies on children (well, I guess it is fortunate, that not many children have the disease).
I would allow the treatment on my child, too, if we ever had to treat for pain, or if she had a hard time in the morning, or missed school, or had to go straight to bed when she got home, etc. She functions just fine, so we are assessing taking the risk for the unknown future - very difficult. It would be easy, if she was suffering in any way right now.
The second one, which goes out three years, interests me more. I mean, only 26% made it three years - and that isn't because the other three fourths were in remission!
Thanks, Jode, but I still have the same question! What percentage HAD adverse events? They tell you who stopped for them, but how many had them? I mean, my daughter had pneumonia, then staph before we stopped mtx. So it took two for us to stop, and that was our decision, not the ped rheum's, so it is doubtful that info would have even madeit into a study. "Parental decision" I believe, they call it?
YEah I know what you mean. Overall I am getting the idea that the meds, most or all of them, only work ( improve or sustain) the disease for a limited time only in many people.
Many people are on a treatment for more than 3 years up to (guessing) 5 or 10? maybeeeeee? I think it depends on the severity of the disease and what the body reacts to.
I would try any of the meds on a child of mine. Whatever helps. I am still not all that convinced with Humira....be it my own experience or the side effects. I know it has helped many people. With Humira, it is great for those who can tolerate it, for those have are more borderline, I don;t think it is worth the risk.......it is the lymphoma that scares me about it.
Best guess is trial and error on any med.
[QUOTE=jodejjr]
YEah I know what you mean. Overall I am getting the idea that the meds, most or all of them, only work ( improve or sustain) the disease for a limited time only in many people.
[/QUOTE]
Huge reason we want to wait - to save that limited time for when she needs it, so we don't blow through them all and have nothing left. It seems like it comes back worse, too, when a med stops working.
lol lmao!
I laughed so hard, not at you but that I feel like I am doing a test for a prof!!!!!!!!!! No offense....just lat laughing at myself....like.....jode! answer the question! lol
What percentage HAD adverse events?
3.7% or 6 subjects in the second study
But that is just a brief over scim, I did not really study it, just pulled the numbers.
jodejjr2008-03-24 09:02:146.5 % or 18 subjects had adverse in the other
I think that is right.
jodejjr2008-03-24 09:00:08Regardless it is not a sig measure.I would be fine with a child of mine taking the eds. Regardless. Try not to worry too much about what will happen in the future and be aggressive in the treatment now. You never know......THey may have more drugs in the next ten years or maybe a cure or isolate a gene.
Since I have been dx, many new treatment options have been developed.
[QUOTE=jodejjr]
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The rates of serious adverse events and medically important infections per 100 pt
-yrs were 5.25, 8.36, and 5.78, and 0.95, 1.97, and 1.98 respectively, for patients receiving MTX, ETN, or MTX/ETN.
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The (low) percentages you list are those that discontinued. I would like to know how these numbers translate into percentages.
For instance, one of these SAEs or MIIs may have later withdrawn under the category 'insufficient therapeutic response".
66% on mtx discontinued the registry, and they give reasons (remission, adverse events, or insufficient effect) for 36.5 % of them.
49% on Enbrel alone quit; reasons given for 15.9%.
49% on mtx/Enbrel quit; reasons given for 21.3%.
That is why I want to figure what was going on in the "per 100 pt-yr" deal. Something made them stop, right?
Yes, something made them stop.....I will reread itper 100 pt-yrs
(part years) were 5.25, 8.36, and 5.78, and 0.95, 1.97, and 1.98 respectively, for patients receiving MTX, ETN, or MTX/ETN.
One case of lupus (MTX)
2 cases of sepsis (ETN and MTX/ETN) were reported.
No cases of lymphoma, malignancy, tuberculosis, or death were reported.
jodejjr2008-03-24 09:43:24jodejjr
I am relatively new here so I mean no disrespect when I ask what field you are in that makes you knowledgable about deciphering these things- I honestly want to know.
When you say the Humira worries you because of lymphoma- doesn't Enbrel have that risk as well? My doctor is thinking I'll need a biologic somewhere down the road and he said he doesn't care which brand I use. I was thinking Humira only because it's less injections...
I am to figure out what PT-yrs Part years means. It is listed in every study I read.
it is used in all sorts of statsand research studies is all I know.
No, I checked and "pt yr" is patient year.
That is what I was thinking. So for a three year study, it would take 33.3 patients for 100 patient years? Right?
Suzanne......."I would like to know how these numbers translate into percentag."
Giggling at myself.....I don't know....but I will work on it.
Wantobe .....I am a geek.....I studied Psychology in college gained my BS but the entire time ( it was an easy major for me) my daughter was having trouble and we learned she was ADD so I poured over studies. Then, on top of it I was dx with the RA so I spent more time in the library over stats and research.
When in my stat class....oh it was a challenge.....I had to study harder and needed help so I read and studied to pass........I was also an English minor and the profs let us do our papers on anything so I did research studies for my psych classes.
THe reason why I did so many papers was to help the profs cause they helped me. Plus in Psych....all you do is read studies and analyze, write it up and and get the grade and on to the next ........till ya graduate. Then it stops and you are lost and regular books at the bookstore are boring! So I read more studies.
What it did was help me teach my daughter about ADD. It also helped me to cope with it and find different ways to help her learn. When you learn the language of the brain and sort of how it works, it really helps you understand the thinking of a person with ADD.
So I enjoy the research studies. I am rusty on terminology though and had problems with the computer programs for stats and methods class.
jode
Very interesting! Glad there are people like you around- when I look at those things my head just swims.
P.S. I have to mention that my daughter is now an avid reader and can read read and understand research studies very well. A LOT of our together timer younger years while I was in colleg was spent on the floor or on the couch pouring over books and looking stuff up and documenting. I attribute her sucess in H.S. and journalism to that.
jode
That's great!
The fact that no more of the regular 'weigh in on research' posters have had any thoughts about this is making me think....it is intended to be confusing to mere mortals and intentionally...incomprehensible????
Edited because I think I made up a word...or maybe I made up one now....don't play Scrabble with me.....
Suzanne2008-03-25 10:06:44lol maybe nobody else knows....dunno. I cannot find the definition nor the explanation for "pt yr" so maybe it is what you said
....""So for a three year study, it would take 33.3 patients for 100 """
the only think I can even guess about would be that it is a formula to make the percentage.???????
Just go with the idea that it is ok to use the meds! lol
If there were 8.36 serious adverse events per 33.3 patients, that seems kinda high. Like what the guys in the first study were saying. I don't think a serious adverse event is nausea or an injection site reaction, you know?
Plus, it's not like the study shows it works that great, right? If it did, than more that 26% would be able to last three years.
If my daughter needed it to function, she would be on it, but if I understand these numbers correctly, the benefits do not outweigh the risks for her at this time.
From the first study:
severe infection requiring hospitalization 1.1 % (2), seroconversion for TB 0.55% (1), severe infection requiring treatment with no hospitalization 1.6% (3), autoantibody formation 1.6% (3), severe headaches with abnormal MRI 1.1% (2), and hyperreflexia 0.55% (1). Of the infliximab infusion patients, 5.9% (6) had a severe infusion reaction leading to discontinuation of biologic agent despite all receiving pre-infusion protocol administration of acetaminophen and diphenhydramine.
Conclusion: The majority of patients tolerated anti-TNF therapy with no difficulty. Although the rates of important adverse events were low, there were serious events reported from our centre including significant infusion reactions necessitating discontinuation of the biologic agent. The balance of risks and benefits of any anti-TNF agent should be carefully considered prior to use for the treatment of children with rheumatic diseases.
From what I would gather,as a parant considering an anti-TNF agent they should decide if that is the only treatment......if there are other meds that work rather well, then stick with those. As in MTX, Arava, plaq, and NSAIDS. I think they are suggesting that if there is no other treament and the child's bloodwork is really bad, then use it with caution but your child may not be able to tolerate it.
We are being to told take this risk on a child who is never treated for pain and never misses school or activities and never slows down until bedtime (even in bed! I shared how she 'rows' herself to sleep!). She gets to lead a normal life on her current meds, with no worries about....abnormal MRIs???? Yikes!!! Hadn't heard that one yet..... The second study:
The Long-term Safety of Etanercept (Enbrel®) in Children with Polyarticular or Systemic Juvenile Rheumatoid Arthritis.
Purpose: To evaluate the long-term safety of etanercept in children with polyarticular or systemic juvenile rheumatoid arthritis (JRA). Methods: This 3-year, open-label, non-randomized registry included patients, age 2-18, with polyarticular-course or systemic JRA.
Results: 601 patients enrolled; 198 received MTX, 105 received ETN, and 298 received MTX/ETN. 131 MTX patients (66%), 51 ETN patients (49%), and 146 MTX/ETN (49%) patients discontinued the registry.
In the MTX, ETN, and MTX/ETN groups respectively, 24 (12%), 7 (7%), and 11 (4%) patients discontinued because of remission,
35 (18%), 7 (7%), and 51 (17%) because of an insufficient therapeutic effect,
and 3 (1.5%), 2 (1.9%), and 1 (0.3%) because of adverse events.
159 patients (26%) have completed the 3-years registry to date.
The rates of serious adverse events and medically important infections per 100 pt-yrs were 5.25, 8.36, and 5.78, and 0.95, 1.97, and 1.98 respectively, for patients receiving MTX, ETN, or MTX/ETN.
One case of lupus (MTX)
2 cases of sepsis (ETN and MTX/ETN)
were reported.
No cases of lymphoma, malignancy, tuberculosis, or death were reported.
Conclusion: Safety data from this ongoing registry support the use of etanercept in this patient population for up to 3 years.
Funded by Immunex Corp, a wholly owned subsidiary of Amgen Inc, and by Wyeth Pharmaceuticals.
According to this study, basically conducted by Wyeth, it is ok to use it ......but the numbers kind of say differently don't they?
so I just don't know. Can you discuss this with your RD? If what she is on is working, like anyone , I would more than likely wait on the ANTI-TNF. THe studies indicate that it will be ok, but like you said the numbrers really are not that great. 26% of the cases made it through like you said......a whopping 42% had insufficient therapeutic effect...that me is significant.
Here is where I think they have their 'wiggle room' - "in this patient population". It is safe enough for kids with JRA who need the relief from pain and disease progression. We would take the risk, for that.
I will be discussing it soon with the ped rheum - thanks for your help in preparing my 'case' LOL.
One of the more upsetting things to me - we have long been told that Enbrel works the best in conjunction with mtx. Doesn't look like it, from this study. This study makes it look like the Enbrel drags the mtx down, doesn't it?
Someone pointed out that "discontinued the registry" does not mean discontinued the med.
That is very true. I was thinking of it in the way we would do it - we wouldn't stop the registry unless we stopped the meds, but that might not always be the case.
Well well well. Seems he's a Humira man now. Says it works better than Enbrel, which he had been recommending for like two years.
So your daughters' RD is recommending Humira? Yes. Not a surprise that he recommends a biologic; just a surprise he has a new fave.
I actually wanted her to start Humira after mtx made her so sick. I had a study and was asking for it. He said Enbrel was better, even called another ped rheum on the Humira study. The other ped rheum said they were the same and 'if you have a mom willing to do a biologic and the mom wants one over the other, just give it to her!', which he thought was so funny that he told that story over and over and over every time we saw him. He was adamant that Enbrel was better; I kept saying he should have listened to the other ped rheum and given me what I wanted instead of going overboard to prove they were the same.
So we didn't do either....
And now after yucking it up at my expense, here we are. Now they think Humira is better. Go figure. She could have been on it for a year now.
But I guess he isn't betting the farm on Humira, either, since he also recommends adding mtx, and an NSAID (which means adding Prevacid again, right?). My daughter was doing the Macarena as we discussed this.
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