Rheumatoid Arthritis News Articles, Vol. 3: Syk inhibitor, CVD Risk & Diabetes Link
3 hot Rheumatoid Arthritis news articles: RA pill, cardiovascular risk guidelines & more!
1 – An oral Spleen tyrosine kinase (Syk) inhibitor for Rheumatoid Arthritis
A recently published study evaluated the effectiveness and safety of a pill being called R788 for the treatment of Rheumatoid Arthritis. R788 inhibits Spleen tyrosine kinase (Syk), an important immune signaling modulator, produced by the spleen. The Syk inhibitor was shown to reduce disease activity in patients with Rheumatoid Arthritis who had not responded sufficiently to methotrexate alone.
This was a double blind phase-2 clinical trial of 457 patients with active Rheumatoid Arthritis. The Syk inhibitor was tested at doses of 100 mg. pills twice daily and 150 mg. pills once daily against a placebo. The results seem to justify phase 3 trials, which may already be in process since studies are usually published a few months after they are completed.
After six months, 67% of patients taking 2 100 mg. doses and 57% of patients on 1 150 mg. dose reached ACR 20. That is a measure for 20% improvement of symptoms according to the American College of Rheumatology (ACR). However, 35% of patients who received the placebo reached ACR 20. That is statistically significant. However, I always wonder whether that means that more than half of the 67% would have improved 20% anyway since half of 67 is less than 35. The nature of most Rheumatoid Arthritis disease activity is to fluctuate by at least 20% over 6 months (from my experience with patients, although my own RA does not do that).
“It was also significantly superior with respect to ACR 50, which indicates at least a 50% improvement,” reaching 43% and 32% respectively, for each dose of R788 versus 19% for placebo. For ACR 70 (a 70% improvement of symptoms), the outcomes were 28% for the 200 mg. daily dose of R788 and 14% for the 150 mg. dose, versus 10% for placebo. (Personally, I think that is more noteworthy since 28 is almost 3 times greater than 10.)
Adverse events which represented possible side effects included diarrhea, respiratory infection, neutropenia (lowered neutrophils, a type of white blood cell), and increase blood pressure.
Read more on the Rheumatoid Arthritis news about Syk. (If that link is blocked, enter: “syk inhibitor nejm” into the Google search bar & click on the top entry.)
2 – Reducing the risk of death by cardiovascular disease in Rheumatoid Arthritis patients
“Cardiovascular disease (CVD) accounts for approximately more than 50% of deaths in patients with rheumatoid arthritis (RA). However, there are no clear universal guidelines for modifying this risk in patients with RA, or other forms of inflammatory arthritis.” Therefore EULAR (European League Against Rheumatism) has created new guidelines to “attempt to address the gap in knowledge.” The study was created by studying literature relating to cardiovascular disease risk in RA and the closely related diseases Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA).
Highlights of the 10 recommendations:
- Control disease activity
- Assess CVD risk in RA patients yearly
- Increase risk factor assessment by 1.5 in long-term RA patients
- Consider use of statins and ACE inhibitors
- Cautiousness with use of NSAIDs
- Lowest possible dose of steroids
- Smoking cessation
“Of note, the level of evidence for all of these recommendations was only moderate (ranging from 4 to 2b) and the strength of recommendations was also relatively low (ranging from D to B).” In other words, the researchers are still uncertain of a way to decrease CVD in Rheumatoid Arthritis patients, but these are the best recommendations they have. They seem to think that if these measures are implemented to a greater degree, we will have an opportunity to determine how well CVD risk could be modified.
Read more on the guidelines for managing cardio-vascular risk with RA.
3 – Genetic susceptibility for Rheumatoid Arthritis linked to Diabetes & Celiac diseases
A gene being called TAGAP has been found to associate with Rheumatoid Arthritis susceptibility. It had previously been found to be associated with both type-1 Diabetes and Celiac disease. These type findings are referred to as “overlapping genetic susceptibility variants.”
Genotyping was done for almost 4,000 RA patients and about 3,500 controls. Researchers suspect that a variation within the TAGAP gene is associated with all three autoimmune diseases.
“This confirms the finding of a previous study showing association of the TAGAP locus with RA but suggests that the variant associated with autoimmune diseases is more strongly associated than that reported previously.” It appears that the current study is more is more specific and so refines and extends the work of the previous study. The results also suggest that the overlap with type 1 Diabetes for RA is stronger than that of Celiac disease.
Read more news about a genetic connection between Rheumatoid Arthritis, type 1 Diabetes, and Celiac disease.
Recommended reading:
- Rheumatoid Arthritis News Articles, Volume 2
- Rheumatoid Arthritis News Articles, Volume 1
- My First Actemra Treatment
Concerning the Gene responsible for RA being linked to Diabetes type 1, I have RA and my son has diabetes type 1.
I hear that all the time Sue. Either parent child or RA patient with both symptoms. It’s definitely a clue. I hope your son is doing ok.
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Kelly, this is an interesting read and something i kind of already knew..i had been by told by my consultant that if you get one auto immune response you are more than likely to get another.. (this was later confirmed by my sister who is a doctor – and had been doing some research at the time) ..as you may already know i have Coeliac disease and RA – both quite difficult but manageable at the moment…trouble is sometimes i don’t know whether its because i’ve had gluten slipped into my food, or my meds for RA that have upset my tummy at times!! all very confusing..
This is a great post and very informative as usual..lets hope these clues lead to further investigations and a cure..
Thank you
Sara x
Thanks, Sara. What kind of doc is your sister?
Interesting. I have asthma, which is autoimmune, and endometriosis, which MAY be. I love the autoimmune illness come value packs. More bang for your genetic buck.
Very funny, Amy. 😛
Genetic arguments for disease always drive me nuts when they’re done like this. I’ll have to pull the article, but with such large sample sizes you have tremendous statistical power to find something/anything.
Interesting news on the Syk inhibitor. I wonder what else this drug hits though. Kinase inhibitors are usually very promiscuous and if you hit one you’re likely to hit a bunch of them. Not to rain on a parade, but celluar pathways are tricky and can find their ways around road blocks leading to drug resistance overtime.
I’ve ran across a number of other experimental drugs lately that have RA activity. I’m still following up on them. I’ll drop you a line when I know more.
Yes, do keep an eye on these and let us know what you like. That will be great. There’s a few in that pipeline right now I hear.
Ahhh. I see you figured out where I work. I told you it wouldn’t be hard. Let’s keep it our little secret. Ok?
We have one molecule that I know of that is fairly far along for an RA indication. I don’t know that much about it though. Even if I did know something I’d dare not share anything unless it is published in the public domain.
Boy those kids sure look happy. Great smiles. Nice to see.
I keep up hope for something. Some times just seeing things like kids having fun is enough to give me some relief. Thank you for what you do. Hang in there.
Phil
Thanks, Phil. Just remembering that day made me so happy this morning. Glad someone else “got it”!!
Annual gingerbread house shoot – Brilliant!!
My dad has had type 1 diabetes for 32 years. I have monitored my blood sugar carefully for years, only to be hit with RA instead.
btw, is gingerbread house season just for 1 day on New Years Day?
Bwhahaha. Yes, I hate to waste the hard as a rock gingerbread house. So, I came up with a good use for it. Doesn’t it look fun?
I’m really struggling with yet another’s secondary condition, neutropenia. The toxcilzumab infusions are responsible and they have been the only treatment that keeps me out of a wheelchair though I’m still flaring to varying degrees. So, when the neutrophils drop to low the medics take me off methoject and the infusions which is frightening as hell.
I was also thinking that sjjgrens is underestimated, when I have a real bad bout my mouth is split open, tongue and cheeks and have had many fillings drop out as you have said Kelly elsewhere. I can often only eat akaline food as it’s so v painful. I’m waiting for my wrists to be replaced now, but as my thumbs have been more painful than my wrists I wonder if it will help. I’m a walking catalogue of symptoms and pain and no one in my life wants to hear about it. Rhuematolgy have given up, the proff said I should accept they have got me as well as they can and I’m now at the top of the treatment tree. I have had to return to steroids much as I hate them and after it took me two years to get off them. And am taking the higher doses of opiates though I won’t return to oramorph as it made me feel so spaced out all the time. After 12 years I can’t even remember all the co morbidities that I have been told I have, the casual oh yes that’s vasculitis, puts me into so much shock (yes I still do get shocked surprisingly) I dread mentioning another new symptom. Now I’m 63 I’m beginning to fear the future more than I have.
When o read your blog on trailing steroids I thought it sounded like you didn’t use them to help dampen extreme flares, I met a woman in Rhuematolgy who has adverse reactions to most of the RD drugs so has to live with it as it comes, she was wheelchair bound needless to say. I have been told I’m in to top 2% of aggression in the U.K. Great! And told its galloping – whatever that brings.
Apologies – I haven’t stayed true to the vein which you were discussing but it sort of poured out.
I meant to add how frightening it is to read what can happen with neutropenia, sepsis another form of immune attack. The body can get totally miswired and send haywire messages that can kill.