Rheumatoid Arthritis, Brief Review of Differential Diagnosis and Initial Treatment
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
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