Rheumatoid Arthritis Brief Review of Differential Diagnosis and Initial Treatment

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this in this next 45 minutes and the  initial treatment of rheumatoid arthritis   dr michael weinblatt will be talking  about extensive treatment of rheumatoid   beyond drugs such as methotrexate we'll  talk about rheumatoid arthritis obviously   we'll talk about how to diagnose it  what is its differential diagnosis   and what are the initial treatments and then  we'll go over some questions and answers   rheumatoid arthritis is a systemic inflammatory  disease primarily affecting the small joints of   the hands and feet and as you can see here there's  swelling over the mcps and pips relative sparing   of the dips which is a fairly classic image that  one will see in extensive rheumatoid arthritis   without treatment this is what one would see  on x-rays with treatment in 2018 this rarely   happens but when you look at an x-ray you think  of at least four things you think of soft tissue   swelling which the patient has you think of  osteopenia which the patient has you see joint   space narrowing which the patient has and you  see erosions you see these little rat bite areas   which the patient has from extensive treated or  poorly treated or untreated rheumatoid arthritis   this is an x-ray we don't want to see anymore but  you have to think of rheumatoid arthritis as being   one of many diseases that can cause arthritis  of the hands in particular this is a patient   with polyarticular gout he was admitted to the  brigham and women's hospital for a flare of his   rheumatoid arthritis but as you can see there  are telltale signs that this is not rheumatoid   especially when one sees tophi over the third  dip so basically though any of the inflammatory   arthritis can cause inflammation along the  mcps and wrists especially the ulnar styloid   now the criteria for rheumatoid arthritis have  essentially changed since 2010. prior to that   when i was a fellow a million years ago one would  make a diagnosis of rheumatoid arthritis based on   these criteria which were which were put out in  the 1970s and what you see here things we don't   want to do anymore you don't want to wait to see  if there are x-ray changes to make a diagnosis   serum rheumatoid factor has now been supplanted  partly by anti-ccp and you don't want to wait   till the patient has stiffness or not or  care if the patient has stiffness or not   you want to be more aggressive about making  the diagnosis and hopefully i'll explain why   as we go along so the new criteria which came out  in 2010 from the american college of rheumatology   in the european league against rheumatism say  anyone who has sinovitis of at least one joint   should be tested for rheumatoid arthritis and  they give it a point system which i'll show on   the next slide and if you have six points if  you will or more you can make a diagnosis of   rheumatoid arthritis and as you can see this is  heavily weighted to the clinical manifestations   if you have many small joints of let's say your  hands ten could be one through five mcps and or   pips you already have five points and if you  have chronicity of more than six weeks you can   make a diagnosis of rheumatoid arthritis you don't  necessarily need a rheumatoid factor an anti-ccp   an elevated sedrate or an elevated crp although  high tied to rheumatoid factors and ccps do play   into the diagnosis of rheumatoid arthritis  more than inflammatory markers the point   of this criteria was for us to treat people  early for us to recognize people early because   earlier treatment will lead to better outcomes  which is the theme of these two presentations   who gets rheumatoid arthritis so who gets  rheumatoid arthritis often there's a familial   aggregation in rheumatoid but the the contribution  of the genes that you'll see in rheumatoid   are approximately 10 to 15 percent and if you  see patients who have hlad hladr4 or ptpn22 and   other genes they do have an increased risk of  developing rheumatoid but other things really   play more important a more important role than  the diagnosis of rheumatoid and the pathogenesis   smoking has been shown to be a quite a important  factor in the development of rheumatoid arthritis   as well as some microorganisms possibly  stress but certainly some environmental   and possibly viral infections but smoking  itself induces the anti-ccp specific antibody   and rheumatoid factors which then leads to a  transition phase which may stimulate the immune   system and those with the appropriate genetic  makeup will then form rheumatoid arthritis so   basically it's environmental it's genetic and  it's of course things we have not yet identified   there's a female predominance to rheumatoid  arthritis three to four to one and the peak   age of onset is anywhere from 25 to 55 years  at age but it can happen at any at any age as   dr nigrovic we'll be talking about pediatric  rheumatology but i've seen patients in the 80s   present with rheumatoid arthritis although the  differential diagnosis would be a bit different   the characters characteristic exam as i  said is a symmetric synovitis for some   reason rheumatoid tends to be very symmetric  but remember it does not have to be you can have   one knuckle in on one hand and not on the  other and still have rheumatoid arthritis   but in particular you'll see involvement of mtps  mcps and pips and a quick exam you can easily   tell if the patient has involvement of these  joints of note is the lumbar spine is almost   never involved with rheumatoid arthritis so if  someone with rheumatoid comes in with severe   back pain you'd want to think of alternative  explanations such as compression fractures   or infections etc so what are the lab findings  you all know the characteristic lab findings are   elevated inflammatory markers said rate and crp  and positive serologies especially the rheumatoid   factor but now more importantly the anti-ccp  antibody high titers of anti-ccp antibodies   highly correlate with rheumatoid arthritis  of course there are always false positives   and false negatives but in general a high tide  or ccp is a high correlation with rheumatoid more   than a high tide or rheumatoid factor which  can occur in many other different illnesses   a simple cbc is a nice way to look at rheumatoid  arthritis as well and is also a nice way to look   for chronic inflammation you get anemia of chronic  disease thrombocytosis and leukocytosis things   you don't necessarily see and let's say lupus  where you'll get leukopenia and thrombocytopenia   if someone has mark leukopenia you want to think  of a condition known as felty syndrome which is   rheumatoid arthritis with splenomegaly ankle  ulcers and usually seropositivity but many of   those patients now upon flow cytometry have large  granule lymphocyte syndrome so that is something   to think of about as well when you have a patient  with rheumatoid arthritis and a low weight count   one of the best features to diagnose inflammatory  illness of a joint is to aspirate the joint   that is something that should always be done in  my my opinion at least once to make sure it's   inflammatory it's not some rare infection  and it's not some unusual crystal disease   the characteristic characteristic imaging i've  discussed uh and again we don't want to wait we   don't want to see this ever again so therefore  we've started looking at mris and ultrasounds   ultrasounds and mris can often  show synovitis and tenocynovitis   after bland physical exams but they're expensive  and not always needed as a good physical exam   can trump an mri or an ultrasound but in some  patients ultrasound and mris are quite useful   to follow the course of the disease and  to follow and to help with the diagnosis   what's the differential of someone who presents  with polyarthritis now polyarthritis means more   than three to four joints the whole group  of diseases we consider are the seronegative   spondyloarthropathies which include psoriatic  arthritis inflammatory bowel disease reactive   arthritis and ankylosing spondylitis now these  are a bit unusual and bit atypical compared to   rheumatoid arthritis in particular they tend  to be large joint asymmetric especially ibd   and spondylitis but a subset of psoriatic patients  can present looking just like rheumatoid arthritis   with psoriasis but with negative serologies those  patients tend to have significant dip involvement   the classic sausage digit which you'll hear  later in this course infections can mimic   polyarthritis in particular viral infections such  as hepatitis c hepatitis b surface antigenemia   activating complement complement and causing  immune complex disease as well as lyme disease   and rarely you can get polyarticular septic  joints but those patients are usually very sick   any rheumatic disease can cause polyarthritis  it's just the extent and the level of inflammation   that is different lupus mixed connective tissue  disease polymyas polymyositis dermatomyositis   can all have ro low grade low grade  inflammation as part of the disease   polymyalgia matic a disease in the elderly which  presents usually over age 50 to 60 is primarily a   shoulder and hip girdle pain syndrome but really  you can have low grade sinusitis over knees and   mcps sarcoid is on everyone's differential but  you can have bone and joint involvement in sarcoid   but the most important thing to make sure the  patient doesn't have is chronic pseudo gout   or chronic polyarticular gout as a mimic of the  photograph i showed in the beginning of this talk   any vasculitis anchor vasculitis and the  like can cause low-grade polyarthritis and   i've seen and we've all seen a number of  patients with anchor-associated vasculitis   who who are seronegative have inflammatory  arthritis and only after years of disease   present with renal or pulmonary disease so in  someone who's sero-negative don't label them   rheumatoid arthritis label them inflammatory  arthritis so you still think of all of these   possibilities as time goes by as i've said  before it's important to make a diagnosis early   the earlier you do the better the patient will do  as well structural damage tends to occur early on   within the first two to three years of disease and  rheumatoid is a progressive not a benign disorder   and slower progression of disease is  linked to early and aggressive treatment   early and aggressive treatment leads to less  non-steroidals and their complications less   steroids and their complications and in many  studies now here in europe less orthopedic surgery   and more and more we're looking to see that  there is a improved mortality and decreased   morbidity in patients treated early and  aggressively who have rheumatoid arthritis   now rheumatoid arthritis i tell my patients  is not just the disease of the joints   it's a disease of the whole system  you feel badly you have fatigue you   may have low grade fevers but you also have  extra organ involvement which we'll go into   heart skin neurologic ocular muscle and  even ent and we'll discuss that among others   the pulmonary manifestations tend to be one  of the more common manifestations we see   plural effusions can be present to 20 or more  patients who are seropositive bronchiectasis   is present in chronic rheumatoid arthritis  pulmonary hypertension vasculitis all forms of ild   described more and more in rheumatoid  arthritis and becoming more and more identified   as a cause of morbidity and mortality in  our patients nodules can occur anywhere   including the lungs and heart and then you  always have to worry about the drugs we use   including methotrexate and others and infections  we cause or infections that happen spontaneously   now pleural effusions as i said is one  of the more common manifestations we   see in rheumatoid arthritis and it's really a  typical board question is what distinguishes   a rheumatoid arthritis effusion versus any  other pleural effusion the pleural effusions   tend to be exudates they can have a low ph but the  hallmark is this is very low glucose and obviously   the patient does not have an empiema so anyone  with a pleural effusion a profoundly low glucose   and clearly is not infected one would always  consider rheumatoid arthritis as its ideology   and the extent of the joint involvement doesn't  necessarily adhere to the extent of the pulmonary   involvement i've seen patients with bland  sinusitis who have pleural effusions but but their   rheumatoid factors tend to be quite high and you  can get rheumatoid nodules anywhere as mentioned   this is a patient with pulmonary disease who has  multiple rheumatoid nodules these can be removed   obviously and if you have multiple ones usually  you do want to remove one which is a lot easier   than it used to be when the patients had to have  a thoracotomy as lymphomas also increased risk in   patients with rheumatoid so i think you do  want to sample one of these if they do not   resolve spontaneously and again you always want  to worry about you always want to worry about   other entities when you see pulmonary involvement  or rheumatoid this is a patient who had mai and   abscess treated with immunosuppressive therapies  so infections are always on the differential of   patients with rheumatoid arthritis and pulmonary  involvement especially those who use our medicines   cardiac manifestations have traditionally  been identified as pericarditis and as you   could see here up to a third of patients in  seropositive groups in the 60s and 70s studied   showed pericardial effusions and occasionally one  would see tamponade and constrictive pericarditis   you can see nodules anywhere including the  heart valves causing complete heart block   artists myocarditis and rarely amyloidosis  coronary artery disease is now probably the   most common manifestation cardiac manifestation of  rheumatoid arthritis there's clearly an increased   risk of cardiovascular disease in our patients  with rheumatoid arthritis and early treatment   may prevent that as you'll see aortitis is also  something you should be aware of studies have   shown that a large percentage of patients with  intractable congestive heart failure may have   aortitis as its cause in patients with rheumatoid  arthritis this is a prototypical picture of the   patient with severe pericarditis it's like if you  have white bread and you put butter on it and you   put the pieces of butter together and you try  to peel off the bread or the pericardium you'll   leave fribinus necros fibrinous exudate this is  a bread and butter pericarditis appropriately   that you have to always consider neurologic  symptoms in our patients with rheumatoid arthritis   obviously any numbness in the arm  or hand you're going to worry about   carpal tunnel syndrome ulnar neuropathies and  peripheral neuropathies and cervical myelopathies   patients can occasionally have  myopathies in terms of weakness   and rarely myositis the myositis of rheumatoid  arthritis will usually only have a cpk maybe two   three times normal and rarely will be in the  thousands even if there is a vasculitis underneath   rare rheumatoid vasculitis can present with  mononeuritis multiplex that is happening less   and less now that we're using aggressive therapy  and and treating patients more appropriately   however in the past when patients were  treated mainly with steroids and nothing else   one would often see rheumatoid vasculitis and  mononeuritis multiplex this is now seen but it   create but very rarely the most important thing  to remember when you see someone with rheumatoid   arthritis especially if they have any disease of  chronicity is to think about the cervical spine   and the brain stem entrapments patients can  have significant problems in the cervical spine   they can have c12 subluxation and myelopathy from  c1 down to c2 it could even involve cranial nerve   to damage the sensory nerve nucleus 5 and as you  get atlantoaxial impaction you can get vertebral   basal or posterior circulation symptoms with  drop attacks cerebellar signs and diplopia   and of course you can get the standard lower  cervical root signs that everyone gets but i   must point out that one should always be aware of  the c12 subluxation especially in a patient with   rheumatoid who has chronic illness and is heading  for surgery so you don't inadvertently pith the   patient when you try to anesthetize them what you  would see in a patient with rheumatoid arthritis   and significant cervical spine disease as this  patient shows is on the lateral you see a fairly   normal spine in in essence although they do have  narrowing here and but basically looking at the   c12 it does not look that abnormal but remember  if ever you're looking to screen for patients with   cervical spine disease especially for c12 you  want to do flexion and extension views and as   you can see when the patient flexes there's this  huge gap between their their anterior arch of c1   and the odontoid which is at least 15 millimeters  it should never be more than three millimeters or   more and what you see in that is the patient is  ultimately being uh not pith but certainly that's   being compressed at the upper portion of this  the uh spinal cord into the brain stem and this   is a patient would have had significant myelopathy  and ended up having an occipital c2 fusion this is   one of my patients who had this done before her  knees and her main symptoms were her knees not   her numbness or tingling or her myelopathy so i've  covered a number of extra articular manifestations   one could rarely see ocular involvement you can  get iritis uveitis and in children you really must   be aware of having the child have an eye exam you  can get sclero malaysia perforance and blindness   but we rarely see that in 2018 i discuss muscle  involvement and you can really get cricoaratenoid   involvement where the patient will have stridor  and sometimes and really needs to have a   tracheostomy and control but again that is rare  in 2018 but was not that rare 20 to 30 years ago   now once the diagnosis is made is made and we want  to make it early only after six weeks of disease   and if the patient clearly has severe symptoms and  it's not six weeks we're not going to academically   wait to six weeks to treat the patient you want  to treat them and you want to explain to the   patient why obviously you want to make them more  comfortable and functional you want to decrease   pain you want to prevent joint damage you want  to prevent disabilities in orthopedic surgeries   and you want to prevent death and morbidity  there's no question that the treatments we have   now do all of these things there is increased risk  of mortality in patients with rheumatoid arthritis   when i first started giving these talks when you  looked at men compared to age match controls they   live six six years less long than the controls  and women live three years less long this is now   approaching it's now approaching the same life  expectancy as you can see these are studies done   by sparks in our group who looked at the life  expectancy of patients with rheumatoid arthritis   and when you look at all rheumatoid arthritis uh  you'll see this is the law this i'm sorry this   this line here but if you look at seropositive  rheumatoids compared to non-rheumatoids there's   a significant morbidity and mortality  in patients with rheumatoid arthritis   why is there this increased risk i mean we  all wondered why there was but i think now   it's more and more clear that in addition to  pulmonary disease it's cardiovascular disease   in meta-analysis in 2008 there's an increased  risk of cardiovascular deaths in r.a approaching   50 percent and in a dutch study the observed  mortality with rora was 54 percent higher   than the general population and dr spock's  recently presented that there's a three-fold   relative risk of pulmonary disease in  sero-positive woman with rheumatoid arthritis   so and there's no question now the treating ra may  decrease the risk of mortality this study by wasco   in 2014 showed looked at examining 56 25 patients  over 20 years there was a 70 decreased risk of   mortality and those taking methotrexate for more  than one year not controlled study but certainly   pointing in the right direction and is probably  because of decreased coronary artery disease also   spocs has recently shown that smoking cessation  within five years of diagnosis of rheumatoid also   decreases the risk of subsequent mortality and  interestingly that as you've probably all seen   there are now a number of our drugs or rheumatic  disease drugs or anti-inflammatory drugs that   are being used to treat or modify carnae disease  there are studies going on looking at colchicine   and the studies going on looking at methotrexate  to decrease cardiovascular events and stroke   and the cantos trial published in the new  england journal by dr ricker clearly showed that   an il1 antagonist kenyakinimab and traditional  therapy prevented cardiovascular events in an mi   in a recent mi population and these are not  rheumatoid patients so when to initiate treatment   for rheumatoid arthritis as i've said many times  early treatments been linked to better outcomes   for many reasons already mentioned now what  do you use what type of drugs do you use   back in the 70s people would use various kinds  of anti-inflammatory and or low-dose steroids and   wait six months a year before you even treated the  patient this is certainly not the way we do it now   and nsaids have become almost an afterthought  they become a mild pain modulator some people   take them daily but most do not because of the  risks including gi and cardiac and most people use   nsaids as one would take a tylenol so what would  you do what do you treat patients with rheumatoid   basically in the american college of rheumatology  guidelines you want to treat to target i mean   the goal of treatment in anyone with rheumatoid  arthritis is a remission or low disease activity   using up using methodologies to to monitor disease  activity but the goal is really remission and what   do you use to get into remission if you have a  dmar naive population with not a lot of activity   you go ahead and use simple drugs but if you have  a very aggressive patient who is not responding to   early therapies you may go right to methotrexate  and antenna set so what you use depends on a how   sick the patient is and what their options are in  terms of their insurance company frankly so let   me go over the various things we'll talk about in  terms of the potential treatment options we have   for rheumatoid arthritis we always use steroids  and someone who really needs a boost quickly   steroids are wonderful drugs in the short run  as you all know horrible drugs in the long run i   always tell my patients steroids unlike any other  drug i use will cause a side effect if you take it   long enough where the others only may other early  therapies you may use are the synthetic demards   hydroxychloroquine sulfasalazine methotrexate and  laflitamide and then the whole world of biologic   therapies and other small molecules are being  developed so are steroids disease modifying drugs   this is a study showing 81 patients with  rheumatoid on prior no prior therapy half   were randomized to six months of 10 milligrams  of prednisone and the others to nothing   after six months uh the patients who had acted  disease could have been given sulfasalazine   what they found is prednisone had a significant  clinical improvement in the first six months had   decreased radiographic progression but obviously  there were side effects with fragility fractures   skin fragility as well so yes steroids work yes  they're disease modifiers in europe they call them   disease modifiers but i am so concerned about the  long-term side effects of steroids that i rarely   use them and if i do and we all do you want to  decrease the dose to as low as possible as quickly   as possible what is a safe dose of steroids  probably no dose but under five milligrams   would be fine but under five milligrams even  three milligrams there's a risk of osteoporosis   skin fragility and glaucoma and cataracts as  well as diabetes so we want to keep steroids   down to a level that is most tolerable for the  patient and add other drugs a simple drug that   obviously people can use is hydroxychloroquine or  plaquenil it's been used for decades and decades   and it's overall well tolerated but  has potential side effects including gi   rash and oculus side effects and you need to  have ocular monitoring for every six to 12 months   now this drug has been as i said around for years  and years originally an anti-malarial drug but now   there's becoming more and more evolution in  how it works and it's being identified as as a   toe-like signal receptor blocker and that is  probably its mechanism of action and certainly   less immunosuppressive than the other drugs  we're going to talk about and since it's so   relatively benign it's used in all of these  conditions at one point or the other but not   really approved for many of these conditions  either now there is a study in 1993 showed it   actually worked this is a small study 126 patients  randomized to 400 milligrams of hydroxychloroquine   or placebo for six months and end point scores  were looked at combine swelling pain tenderness   and not to read this slide but overall there's  a forty percent greater mean improvement   in patients who took hydroxychloroquine versus  not and more patients were judged to be improved   according to global assessments so it does work uh  it's a modest disease modifier if it dot modifies   this disease at all but it's a useful drug to  have especially in that patient who has rheumatoid   arthritis we would consider seronegative blood  test negative you do always worry about ocular   toxicity with hydroxychloroquine you have to  keep the daily dose less than 6.5 milligrams   per kilogram in general uh and you want to if  someone weighs about 130 to 135 that's when you   have to start looking at modifying the dose  you can do a lean body weight formula and i   look it up on wikipedia which uh uh is a little  more complicated than i tend to use so i would   look at this 6.5 milligrams per kilogram and who  gets who has increased risk of ocular toxicity  

it's cumulative total more than more than  a thousand grams more than five years renal   and hepatic dysfunction and greater age i have my  patients see the ophthalmologist every six to nine   months often the ophthalmologist in the beginning  will not see my patients for six to nine months   because they almost never see this toxicity and  then this one patient developed acute generalized   exanthomatist pustulosis which is induced by  hydroxychloroquine it's like a severe burn   over 95 percent of her body she was hospitalized  she became bacteremic but she totally cleared   which is the story with this condition patients  almost al always do get better from this and it's   extraordinarily rare another thing with long-term  use of plaquemines that you have to consider is   is cardiomyopathy we'll see this once or twice a  year in patients who were given hydroxychloroquine   over many years without appropriate monitoring  or adjusting for weight and they could present   with cardiomyopathy or complete heart block and  there have been classic biopsy findings showing   curvilinear bodies on em and there was a  classic paper in the new england journal   where actually uh when plaquemines was stopped  the uh there was another endocardial biopsy   which showed resolution of these findings  and it's a rare cause of myopathy as well   another early drug that we use is sulfasalazine  which is part of triple therapy which i'll mention   it is relatively safe it is very rare if any  long-term side effects but it can affect the   bone marrow skin lung hypersensitivity reactions  gi toxicity and rare azospermia the latter is an   important thing to mention as occasionally i'll  see patients who are trying to get pregnant and   and the male was not aware that that this drug can  cause that side effect now what changed the face   of rheumatoid arthritis is the the introduction  of methotrexate and methyxate's been around   since the 1950s in one form or the other but as a  paper that was uh initially published in the new   england journal in 1985 that showed the efficacy  of low-dose methotrexate and rheumatoid arthritis   this was a paper there was a double-blind plus  placebo crossover trial and it was a very small   study but the results were so profound that it led  to uh publication and was this was the paper that   led to fda approval as as an effective drug for  rheumatoid arthritis and it's now the standard of   care it changes the natural history of rheumatoid  it decreases the extra-articular manifestations   and increases quality of life and as i've shown  before i do believe it increases survival and   decreases cardiac risk and it's easy to give  first of all you want to get between 15 and 25   milligrams weekly you'll start at 7.5 milligrams  weekly you have to make sure the patient's aware   that it's a once a week dosing you always  use folic acid with it and occasionally if   someone has trouble taking the drug you'll  use pholinic acid at doses of anywhere from   five to ten to fifty milligrams weekly  but pholinic acid when administered has   to be given 8 to 12 hours after methotrexate  dosing did not block the effect of methotrexate   methotrexate above 15 milligrams is not  as absorbed as well there's not a linear   absorption once you get to 25 milligrams once you  get to about 15 milligrams we often split the dose   you still use it once a week but you use it once  in the morning and once in the evening once a   week or even better you use injections you use  subcutaneous dosing which is uh which i have found   to be actually spectacular in a subset of patients  who have mild to modest response to methotrexate   but switching the patient to sub-q makes all the  difference in the world there are potentially a   lot of side effects of methotrexate but it's  very they're very rare in terms of long-term   side effects you can commonly get upset stomachs  liver abnormalities blood count abnormalities   lung toxicity rarely nephrotoxicity okay the only  malignancy it may be associated with is lymphoma   but that's unclear i think it's less associated  with malignancies than any of the other agents we   use beyond methotrexate and it's rarely associated  with infections and opportunistic infections   but overall with appropriate monitoring  i think it's an incredibly safe drug   compared to the alternatives we have at this  point before you put someone on methotrexate you   need to make sure their liver function is fine  their kidneys are fine their blood counts fine   they haven't had hepatitis exposure in the past  and they've been appropriately immunized and that   methotrexate does decrease antibody formation  to various vaccines so before i give anyone   methotrexate i want to make sure they're up to  date on their flu vaccine they begin the prevnar   and pneumovac series and talk about other live  vaccines such as zostavax or some of the drugs dr   weinblatt will talk about as well as methotrexate  to increase the risk of shingles however with this   new zaster vaccine that can be given at virtually  any time to virtually any patient in addition   you want to be sure the patient doesn't have  tuberculosis history and you'll do a ppd or a   t-spot some will say you need to do a chest x-ray  prior to therapy i would say that's optional but i   would tend to do it in elderly patients so i've  gone through methotrexate it doesn't work what   do i do then other options are liplitamide  which is a pyrimidine synthesis inhibitor   it's a simple dosing it's a daily therapy it works  within one to two months has a similar side effect   profile methotrexate but i in my experience it  has more toxicity especially gi toxicity some   neuropathy and some liver toxicity and it it has a  long half-life of of 14 weeks 14 days excuse me in   14 days so it's it won't be eliminated from the  body for about two plus months so when women of   child bearing age you probably do not want to use  this drug because it's terratogenic so in women of   child bearing age i would use methotrexate as long  as there's appropriate birth control in place but   i would tend not to use lafletamide because of the  long half-life and potential teratogenic effects   now okay methotrexate's not enough  lafletamine didn't work what am i going to do   and this patient has only a modest response or not  a great response we do have a number of options   dr odell has populized triple therapy which is  adding to methotrexate sulfasalazine and plaquinol   and some patients in fact will start out with all  three therapies and someone who's seropositive   and has a high risk to go on and develop erosive  and inflammatory disease azothiabin's been used in   the past but really is not very effective and then  after that we use the biologics we'll i'll discuss   so how do you decide what to use when the patients  fail the traditional therapies you look at disease   management scores as i mentioned there's das  c dye among others rapid three you see if the   patient has radiographic progression but i said  we never want to see that uh you want to make sure   there are no contraindication to use using some of  these drugs such as a history of lymphoma you're   not going to use anti-tnf etc and then more  importantly as i mentioned before you have to   do an economic review of systems in that some of  these drugs beyond methotrexate are prohibitively   expensive to some patients so dr moral and looked  at what happened to these patients with early   early rheumatoid arthritis compared  oral triple therapy versus a tenorcept   plus methotrexate and early aggressive rheumatoid  arthritis and as you can see there were four   treatment groups immediate methotrexate and  tendercept immediate triple therapy step up   from methotrexate to tenorcep plus methotrexate  and step up from methotrexate to triple therapy   and the endpoint was a dos scores which were  improved and the length of study were two years   in conclusion there was really no difference  in any of these groups overall in terms of   clinical response but there was less radiographic  progression in in the step-up group as in the   step-up group to uh a tenercepter methotrexate  then methotrexate to triple therapy so this is   a maybe a signal that we need to use biologic  therapies earlier but the radiographic change is   is modest at best but overall clinically there  was not a huge difference or any difference at   all in the two groups dr odell then looked at  therapies for active rheumatoid arthritis after   methotrexate failure these are patients who've  already had inadequate responses to methotrexate   what what did he do here this is a very excellent  study patients were randomized to either triple   therapy or triple therapy with methotrexate and  they were crossed over 24 weeks if they now were   not responding and the outcome was what happened  at 48 weeks and basically there was almost   no difference in the two groups triple therapy  was non-inferior to tenorcept in methotrexate   and das 28 scores disease activity scores improved  at 48 weeks for both groups now buried in this is   that patients who had terrific responses with  acrs of greatest 70 percent more often happened   in the methotrexate and the tenorcept group but  this study does show that there's some suggestion   that there's not a whole lot of difference whether  you use methotrexate and or tenecept versus triple   therapy now why would you do that in any event  and the reason is these are in dollars uh for many   years ago you'd want to triple this the cost of  a batacept and a tennercep now now approach fifty   thousand dollars and the cost of monthly triple  therapy as hydroxychloroquine has gone up in price   certainly are dwarfed by the cost of fifty  thousand dollars they're still in the hundreds   thousands a hundreds at most monthly so this is  a big reason why one would go ahead with triple   therapy first the problem with triple therapy  is adherence a lot of patients can't stay on   that quantity of pills and the rapidity of action  is much better with methotrexate and the tenorcept   which is most rheumatologists use rather  than triple therapy now this is what we tell   our patients try to focus less on a cure and  more on the treatment you can afford so that's   unfortunately where the rheumatology is going  with the price of all biologics approaching   50 000 so what are your treatment decisions how  do you decide what the patient should take next   you look at time to response how quickly  do you want to respond occasionally i'll   use methotrexate and antenna step first if the  patient is basically bed bound or wheelchair bound   patient adherence is an issue as triple therapy  often is very difficult for patients to adhere to   and if there's progressive radiographic  progression will want to be   very aggressive and ultimately come down to the  patient's preference and the patient's insurance   preference so that's how we make this decision  and even after you fail let's say a tenorcept   or adalumab and methotrexate and the drugs i've  already mentioned we now have incredible number of   new options and this has not changed even though  it says 2017 and 2018 we have the same options   five anti-tnf therapies and io1 receptor  antagonists which is not very helpful   abatacep rituximab tosoluzumab other il-6  inhibitors and tofacidantive which is the   oral jack inhibitor so these are all incredible  options for our patients in 2018 which they didn't   have as recently as 30 years ago now in summary  rheumatoid arthritis is a treatable disease   early treatment is key less joint replacements  and improved morbidity and mortality there is   no question about it and it really does upset  me when i see patients who have been treated   with inadequately whether it's methotrexate  or antennacept or triple therapy for months   and months and months and did not have a change  of therapy as the disease continued to be active   a plea if you're a primary care provider please  refer to a rheumatologist refer to confirm the   diagnosis and initiate treatment because  a delay of a year in this disease can be   quite significant for the patient but this  is all the caveat this is all modified by   the course considerations that we have but  there are many options and most patients can   find a drug that is a affordable and b incredibly  useful so we'll now go over a number of questions   the first question is a 58 year old male patient  presents with polyarticular pain that has lasted   for six weeks he's had fevers and weight  loss and has a history of traveling to cape   and the vineyard he has morning stiffness shoulder  hip and mcp pain on exam normal physical exam   except for mtp squeeze tenderness upon palpation  and a small right knee effusion so think about   this he's had the disease for six weeks that's  something obviously we've talked about he has one   swollen joint so that's all you need to unlock  the key to possibly having rheumatoid arthritis   he's been to the cape and vineyard uh so  obviously you know i'm thinking about other things   and he's had some low grade fevers and weight  loss which one can see in any of these conditions   so question one as part of the evaluation all  should be a part of the initial work up except   chest x-ray and hand and feet films lime  tighter and a a rheumatoid factor and anti-ccp   a diagnostic tap of the knee a sed rate and a crp  so what wouldn't you do if you have these options   these options are always couched by the way one  writes test questions but essentially the answer   would be a chest x-ray and hand and foot films  now ideally i'd probably want a chest x-ray but   you don't need hand and foot films the other  things you you don't need in detail you   you would want a lime tighter i don't think you'd  care that much about an a a but you definitely   want to limetide it because of his history you  definitely want a rheumatoid factor in ccp and you   want inflammatory markers but the most important  test you really want is the diagnostic test of the   of the knee to make sure it doesn't have crystals  you could even do a lime pcr on it if you forget   to do the lime tighter so the knee tap would  be the most important the chest x-ray and hand   foot films would probably not be very helpful at  this point especially as the onset of this illness   is six weeks so his hand and foot films would  not show any erosions and it's unlikely he has   a pulmonary disease at this point although one  would probably get a chest x-ray down the line   question two a 48 year old man presents with  rheumatoid arthritis he's trying to decide   what uh drugs to take he has erosive disease  has a history of travel to russia and peru   and has a vague sulphur allergy his labs are  unremarkable except for creating 1.7 and the alt   of 54. so as you could see i'm getting to what  shouldn't he take and why shouldn't he take it   so all tests should be done before  deciding the next therapy except   chest x-ray ppd or t-spot pneumovax or prevnar hcv  and hepatitis serologies ace level and s-pep so   what should you do and shouldn't you do before  deciding on next therapy you really don't need   an ace level it's almost never helpful even when  you're thinking of sarcoidosis and this pep is   always interesting but it's really not going to  be helpful so you with an elevated creatinine alt   methotrexate and athletamide may be  contraindicated so answers a b c and   d are required to initiate any biologic therapies  you want to get a chest x-ray before you consider   a biologic usually you want to make sure the  patient doesn't have tb you want to get them   appropriately vaccinated and you want to make sure  they don't have hepatitis dormant hepatitis c or b

2022-01-15

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