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Walsh Aidan AICUR 2021

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AICUR 2021;

Okay so hello everyone thank you for having me my name is hayden welsh and i’m one of the final year medical students from the ul school of medicine so today i’m going to be presenting a project i did for my final year special study module and it was a tanner set for ankylosing spondylitis a systematic review so what i’ll do first of all is just introduce the

Topic and then talk about what the gap in the literature was the methods for the review the results i obtained and the clinical applications of those results and then i’ll finish off just by going through the strengths and limitations of the paper and the conclusions that can be drawn from it so first of all what is enclosed in spondylitis it’s a chronic autoimmune

Rheumatological condition and it’s associated with the hla b27 gene so it’s part of the seronegative spondyloarthritis groups of conditions it can lead to pain and reduce quality life and inhibit function through axial so via the spine or non-axial non-axial symptoms so a typical patient is a young male with a sore stiff back that gets better at movement and exercise

And it’s worse at nighttime and with rest and usually for mild cases we can use simple strategies like exercise and analgesia but for refractory cases the recommended treatment strategy is these tnf inhibitors so for those of you who don’t know the germ necrosis factor factor is a pro-inflammatory cytokine so it’s driving the inflammation in the background which

Is causing the disease so examples of some of these tnf inhibitors are the the map drugs so adelimi map gallimim and fixemap and then it intercept is the one that we are focusing on here so it intercepts itself it mimics the receptor for a tumor necrosis factor so therefore the tnf is going to go bind to it instead of the actual tnf receptor so it’s inhibiting

Tnf basically it’s a tnf blocker so what was the gap in the literature i was interested in this because i saw a few of these patients in clinic and a background in physiotherapy as well so i had seen it in physio too so i went to see what the strength of the literature was for this drug and what i found was there was no cochrane review on the subject since 2015

And there’s also no review of the drug that examined non-radiological outcomes so the only one available just looked at x-ray findings and there is no review of rcts or randomized controlled trials and finally there’s no review involving a thorough critical appraisal and we know that’s pretty much as important as the studies themselves nowadays is to critically

Appraise them and see if they’re any good so i felt there was a need to review the latest evidence here to inform best practice and that led me to three simple aims so i had to systematically search and collect the evidence i then had to assess the quality of the literature and i had to summarize best practice in this domain so once i figured out what the gap was

I went about designing the question and i used the pico method i’m sure you’re familiar with for that so in terms of study design i chose rcts only because this hadn’t been done so far i was only able to analyze english language papers obviously just for logistical region reasons and in terms of my participants i chose those over 16 and diagnosed with as criteria

So that’s the enclosing spondylitis international society and it’s basically the steering group for diagnostic criteria and treatment of ankylosing spondylitis in terms of interception intervention it was the tenor set both as a monotherapy and a public therapy and in terms of comparisons i was looking at everything else so pharmacological and non-pharmacological

Except for biosimilar products which were a different domain and my outcomes again were those recommended by asus in terms of pain and disability because previously only imaging findings have been looked at so i followed the prisma guidelines and on the 10th of august i searched online databases using the keywords that were involved in my pico and i expanded these

And searched them i also searched relevant bibliographies and contacted the authors in the field and then i used the rob2 tool which is cochrane’s recommended tool for critical appraisal and i summarize the results by narrative because there’s no meta-analysis available so i found over two and a half thousand papers and after i screened them removing duplicates

And screened them by title and abstract those left to 21 and after final review there’s 17 left over so there are 17 studies included and the trial durations there was a large range so between six and a hundred and two weeks uh overall there was over two thousand patients and about a quarter of those were female aged between 22 and 47 and the disease duration

Also ranged from two and a half to twenty one years so we can see that the majority of the studies looked at antenna set versus placebo and some studies compared it to other therapies including infliximab subfasalazine and the novel therapy in asia called need in life therapy that was just one study so i went about appraising the studies using the rapture tool

And i found that four of them were high risk four had some concerns and nine were low risk and uh most of the concerns were regarding randomization and deviation from treatment groups as well as reporting of outcomes so most of the papers used patient reported outcomes which obviously could have been influenced by the fact that the patients knew what a what drug

Or treatment they were getting so that was the downfall of most papers but overall there are high enough quality and then i looked at what were the clinical implications that he’s finding so of the high quality evidence we know now that a tendercept is superior to placebo in terms of both clinical and serological outcomes which is something that wasn’t really

Reviewed before and there’s also high quality evidence that it’s better than sulfus alasine which is one of the immunosuppressant drugs there is matter quality evidence that it was actually inferior to one of the other monoclonal antibody drugs infliximab and there is low quality evidence that it can improve imaging outcomes in terms of mri and ultrasound findings

And importantly it was well tolerated and it was flexible in terms of how to give it so in terms of achieving remission you can either give the dose weekly or twice weekly and for maintenance you can just give 50 milligrams once weekly and this is good because it means it has a low patient burden they just need one treatment a week so in terms of strengths for

This study there were six new studies since the last cochlear interview the subject that i identified and it was the first systematic review to examine rct specifically for each intercept which i thought was a bit mad considering how common it is in practice and it also included a thorough critical appraisal section unfortunately the limitations were that there

Was no meta-analysis so we couldn’t pool the data there was language bias in that it was only english language papers and there’s selection bias because i was the only reporter involved and as i said there’s mixed methodological quality and a lack of long-term data we know it’s a lifelong condition so to conclude what are the take-home messages from the paper and

It concluded that attainercept was a safe effective drug frank closing spondylitis and it improved the range of clinical radiological and serological outcomes which was important it was also flexible in terms of dosage regimes and it has a low burden in terms of the patient but the quality of the evidence was mixed with a lack of comparison to other tnf inhibitors

So our areas for future future research future research should focus on younger demographics because we notice the disease affecting young people head-to-head studies versus other tnf inhibitors are needed and future studies should employ a stronger methodology with better blinding so thank you all for listening here are the references to the papers and i welcome any questions though

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Walsh Aidan AICUR 2021 By First Seven Weeks