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Hi. This is QD Video brought to you by RheumNow Live. Today's case is about when I would use an Akinra or an IL-one inhibitor. So a 48 year old woman comes in. She has long standing, what I would call refractory RA, she's failed several TNF inhibitors Actemra, tofacitinib, abetacept and the question is would you now consider you know, a combination of drugs, Rituximab or Anakinra?

Anakinra always seems to get left off the list. I'll remind you it is a drug that is FDA approved for use in rheumatoid arthritis where it was shown to be really effective in multiple trials that led to approval. But yet, it falls off of everyone's list because everyone believes it doesn't really work. Well, that's not true. I've actually used it in Rheumatoid Arthritis with great success.

I must say much less in recent years compared to when it was first developed back in 2002. So, the question is, when would you or should you use, an IL-one inhibitor or anakinra? There are three IL-one inhibitors on the market. One is Anakinra which is only approved for use in rheumatoid arthritis and NOMID, that's one of the three types of caps. Second is Canakinumab also known as Ilaris, that's approved for use in systemic JIA above the age of two, CAPS, FMF, Familiar Mediterranean Fever, Hyper IgD syndrome, and TRAPS.

Yes, it works in TRAPS, maybe better than using Enbrel. And lastly there's Rolanicept also known as Arcalist, it's only approved for CAPS, that's again the three periodic fever syndromes, Mucklewell syndrome, NOMID Cynca, and Familial Cold Auto inflammatory syndrome. Again, only one of these three TNF inhibitors is approved for use in patients with rheumatoid arthritis. So, I think you should know the data about it. It is FDA approved, again you really can't compare FDA registration trials, and you might say that it actually had a lower, ACR 20 response rate compared to some of the other drugs, not that much lower, and actually was similar to that seen with, infliximab in the, ATTRACT trial.

But nonetheless, there are a number of different studies that have looked at the comparative efficacy of Anakinra in RA, and they all pretty much say the same thing. They say that it generally is less effective than other biologics, and when other biologics are looked at, especially in combination with methotrexate, they're all sort of equipotent. So there isn't good evidence that TNF inhibitors are better than IL-six inhibitors or abatacept or rituximab or whatever. But there may be, again, network meta analysis data that maybe it's a little bit lower with anakinra and that's why when you have 11 or 13 different choices as far as DMARD therapy, you don't have to use anakinra, a daily injection. But it has also been studied in a randomized trial in early RA where it was not shown to be any more effective than taking methotrexate alone.

So methotrexate alone versus methotrexate plus anakinra, everybody got better but the addition of anakinra wasn't sufficient to advocate for it. That was a Cardero study from 2016. So, again, who should get anakinra in my clinic? Patients with or suspected as having Still's disease or systemic JIA. That's a no brainer.

That's the first line therapy. You might want to use steroids while you're still working them up, again, it's almost an empiric diagnostic trial if you will, because they'll have a sort of gigantic prompt response. I think that undiagnosed suspected auto inflammatory disease, the use of anakinra or other IL-one inhibitors may be important. But here the issue is, you know, do you use the daily Anakinra or the less frequently dosed, Ilaris or Canakinumab? Generally my scheme has been to use daily Anakinra, get them under control, show that they have sustained efficacy, and then try to transition them to a drug that's taken less frequently which is mainly going to be, ILARIS also known as canakinamab.

What is the other indications? Well, I will use it in RA after patients have failed at least two or three other biologics. I will use it in people declared as being difficult refractory RA when I'm trying to investigate whether another mechanism is underlying inflammatory arthritis. So if you've sort of failed, the approach of inhibiting TNF, inhibiting IL-six, going after T cells, going after B cells, maybe going after IL-one makes some sense. It may also be a drug worth using in patients whom you cannot use other biologics or TNF inhibitors.

For instance, patients with, Hepatitis B, especially acute infections or even those who have, recovered from Hepatitis B and you're worried about it, patients who've had past, fungal, infections that have been a deep tissue fungal infection for which biologics and TNF inhibitors may be contraindicated. Same for TB, and also for patients who are on intravascular BCG, they can't receive TNF inhibitors, they certainly could receive other MOA biologics including Anakinra. I generally do not use them where it's been written about but not FDA approved, that's where it's been shown to be effective in acute gout, in acute pseudo gout due to CPPD crystal deposition disease and in type two diabetes. Although there's evidence out there for their efficacy, I just haven't needed to use that, in any management of any of my patients. So that's it for QD video.

Check out roomnow.live. It's a meeting for curious mind bending rheumatologists who want to be in the know and who want to be good teachers. Check out roomnow.live and register. This is QD clinic brought to you by RheumNow live where you can connect, learn, and interact maybe better than any other meeting. This case is called the problem with pain.

So I have a 48 year old male who is well controlled with his rheumatoid arthritis. It's zero negative, and yet he has pains. At any one visit on a scale of zero to 10, it's a four, five, six, and he always has pain even though he has no synovitis and he's taking a biologic and a DMARD. The question is, how does he manage pain? He's certainly entitled to pain even though his RA is well controlled because he's had RA, he's had antecedent inflammation that's left him with structural changes, some degenerative changes, maybe some periarticular changes that can contribute to pain, and that will come and go with weather activity, etc.

So pain management is a big part of this person's disease control because they attribute that pain to their RA when in fact it may not be from their RA. So first off, is a symptom that is patient driven. It's not one that you can adequately assess by any other measure other than a 10 centimeter, 10 visual analog scale, how much pain do you have. And it's something you can follow time to time. Everybody's different.

A little bit of pain to this one is a lot of pain to that one. And, again, you just have to manage it as best you can by understanding it and understanding the patient and the context within which they get their pain. The problem with pain management is it's either too much, too little, and seldom just right. Now over management largely occurs when the patient is treating themselves or when you have multiple people in the mix treating the pain. And over management can get the patient into trouble with toxicity.

So class example is you're giving a non steroidal and the patient's taking an over the counter non steroidal at the same time. We want to avoid self management. I remind my patients a little tongue in cheek that when a doctor treats himself, they have a fool for a patient. When a patient treats himself, what do you think is the story there? It's not gonna nearly be as nice as the fool for a doctor patient.

Fool for a patient doctor. So you have to instruct them that they need to get smart advice from people who manage pain. If not you, then send them the pain management. I don't send them the pain management generally because most pain management doctors are looking to do procedures and make money. Very few of them want to do chronic pain management and people with chronic pain problems.

The bottom line in pain control is knowing where their baseline pain comes from and what you can do about it to manage that and then to manage when their pain gets worse. First, you know, Ben Franklin said an ounce of prevention is worth a pound a cure. Jack Cush says an ounce of prevention is worth about, you know, 25 pounds of less heartache and trouble for both you and the patient. So prevention is easy. Lifestyle modification, weight loss, and better sleep are things that can help to manage pain.

But most important and the problem with this particular man in managing his pain was he was doing what all patients do. They wait until they don't take they have pain all the time. They don't take pain medicines regularly. They wait until the pain overcomes them, because until then, I'd rather just deal with it, doc, or I can manage it, doc, or I wait until it's bad enough, doc, and then they go and try to take a little Tylenol, a little Advil, a little something, and it's a little too little too late, and they're always in pain, more or less, and usually more. So the goal here is that people who have chronic daily pain, more or less, need to be have their pain prevented prophylactically.

So my way of controlling baseline pain is to put someone on a long acting acetaminophen, six hundred fifty milligrams, two pills twice a day, three pills once a day in the morning. If they have no liver disease and have normal LFTs, could take up to six pills a day, no problem. And that's all forms of acetaminophen, assuming they're not on narcotics with acetaminophen in it. But that would be their daily pain control medicine. Three, Tylenol arthritis every morning, or if their pain is melee at night, every night.

And then they need a strategy to rescue pain. And that would be to use PRN, other agents like low dose over the counter Advil, or a prescription non steroidal or, intermittent tramadol. If they need more than that and a strong narcotic, they're gonna have to go to pain management and hope that that works out for them. Pain management can be difficult, but it really takes a good dialogue between you, and your your patients to best control the pain. I wanna talk to you about the faculty at RheumNow Live.

It's incredible. We have an incredible faculty. Just our first day, our faculty includes Kevin Winthrop, Roy man, and John Giles talking about TB zoster, advanced therapies in RA and cardiovascular risk. Then we have Bevra Hahn, Nicola Dalbeth, and Dan Wallace talking on the history of rheumatology. And then we have Chris Richland, Alan Mentor, and Jose Cher talking about management of psoriatic disease.

It's just an incredible lineup, and not just the first afternoon. There's three other half day sessions that we're going to do from Friday afternoon till Sunday morning. Go to rheumnow.live to register before all the seats are taken. This is QD Clinic, and I'm doctor Jack Cush from roomnow.com. QD Clinic is brought to you by roomnow.live where every seat is a great seat at RheumNow.

Our case this week is inflammatory hips. Just saw this case a few days ago. 49 year old white female comes into clinic with a five year history of bilateral hip pain. You know, it's the kind of hip pain that's actually hip pain. It's in the groin.

It hurts when she does stairs. This is not really low back pain. She's got a little low back pain. She's got a little spondylosis of her lumbar spine, but that's not her major problem. Her major problem is last five years, her hips in the groins have been hurting, and it's been getting a little worse.

She has no other history, little hypertension, takes very few medicines, has been tried on two different nonsteroidals with no benefit at all. She has some labs done, no evidence no evidence of inflammation, sed rate CRP are normal, no serologies were done, X rays were done, and very interesting. She showed bilateral concentric loss of joint space. Superiorly, on the acetabulum, there's some sclerosis. Beneath the femoral head there's some ring osteophytes, but there is this sort of, again, concentric uniform loss of joint space in both hips.

The question is then, what's her diagnosis and how are we going to treat this? So the real issue here, I think, boils down to the X-ray findings. She has no other features to suggest another arthropathy, other inflammatory arthropathy, or spondyloarthropathy. If this were rheumatoid arthritis, there would be that concentric uniform loss of joint space, and there was no obvious evidence of erosions, but there was some irregularities that I'll bet if we had an MRI there might be erosions there, but that doesn't help you if you're looking at spondyloarthritis versus RA. They could both give you erosions.

And so the question then is what other clues do we have? In rheumatoid arthritis, you have this uniform loss of joint space without any reactive bone. In patients who have spondyloarthropathy, there may be a sclerosis and there may be osteophytes. That is also seen by the way also in pseudogout. So turns out that that's probably the more likely diagnosis here that it's a spondyloarthropathy and or pseudogout.

Now how likely is a spondyloarthropathy ankylosing spondylitis to show up, by the way her SI joints are totally normal, at at least by X-ray, you know, MRI might show something different. But how likely is the spondyloarthritis to show up at age 40 in a woman? Well, do know women don't present as men do with spondyloarthritis, they present much later in life, pain is a big issue and function can be a big issue. So this is certainly within the realm of possibility for a spondyloarthropathy. RA, there's no evidence peripherally of anything as far as a symmetric synovitis.

So that's our differential. This is spondyloarthritis first. This is could be infection second, TB, brucellosis. We're here in Texas on pasteurized milk from Mexico, either in the form of milk or milk products and cheeses could lead to brucellosis of the spine and or hips. And then lastly, I guess, CPPD.

So we were gonna get other x rays to look for CPPD, we were going to get an HLA B27, and then we're going to treat the patient. The question is how do you treat her? Do you she's been on nonsteroidals, no no benefit. What if you gave her intra articular steroids? That would help if this were inflammatory OA of the hip or an osteoarthritic or degenerative process, may not help very much if it's a spondyloarthritis, and we don't think this is rheumatoid at this point.

You could just give her an empiric trial of a TNF inhibitor. We did that, we'll wait and see what the lab show and what her response to therapy shows. We'll know within two, three, four injections whether that's the right thing to do or not. If not, we'll worry about pseudo gout and chondrocalcinosis and look for evidence of calcium deposition in cartilage elsewhere in the body, although she's not symptomatic in her hips or not in her knees or her wrist. Really interesting case, I think that I thought that you would enjoy that.

Really interesting program at RheumNow. I should just show you what's on our auto inflammatory session, which is gonna be on Sunday morning. We have some giants speaking at this session. Hal Hoffman from UCSD basically invented the inflammasome and is world renowned for his work in auto inflammatory disease and familial cold or inflammatory syndrome. Dan Kastner from the NIH, you know, is going to talk about how they work up and evaluate patients with febrile disorders.

And then Nicola Dalbeth from New Zealand, Auckland, New Zealand is gonna talk about gout as an auto inflammatory disease. I can't wait for the q and a session with those three heavyweights. Roomnow.live. Register now. This is QD clinic.

I'm Jack Cush from RheumNow. QD Clinic is brought to you by RheumNow live. Great meetings like this need great rheumatologists like you. Today, we're gonna talk about vasculitis by the numbers. So recently went to a conference on vasculitis and a large discussion broke out about how you, monitor and manage these patients.

Certainly diagnosis is a challenge, therapeutics is a challenge, but really I think there's a lot of unknowns and a lot of art to monitoring and assessing patients who have vasculitis. And I thought I'd bring this up in this edition of QD Clinic. And I think you have to look at this maybe from the size of the blood vessel. All vasculitis discussions usually center around size of vessel, and I'll give you three groups: small vessel, medium vessel, and large vessel. So small vessel vasculitis like you see with HSP, palpable purpura, some small vessel vasculitides due to drugs, Behcet's, etc.

You know most of these are you see what you get or you get what you see, I guess you should say, in that there's not a lot to be gained by laboratory investigations or other assessments or looking for organ damage, other than what you can obviously see by a good clinical exam. If you move on to larger vessels, meaning medium sized vessels like you might see in ANCA associated vasculitis, there there's a bit of a bit more of a challenge. Certainly you're going to assess patients based on the presentation and organ system involved in someone with ANCA associated vasculitis. So if it's just upper respiratory, if it's lower respiratory, if it's renal, if it's other organs or skin, clearly symptoms and signs and clinical assessments are very, very important. Labs, for the most part, not so important, meaning Sedrate CRP don't pan out very well.

Renal function becomes a problem when renal function is a problem. And then, you know, monitoring creatinine, blood pressure, and urinalysis might be important. But the real issue is whether you monitor ANCA levels. And for me, that's a little bit like double stranded DNA in lupus. So, know, what twenty, forty percent of patients have, double stranded DNAs with lupus and maybe half of them will the levels of double stranded DNA correlate with disease activity.

The other half, they're positive and they're always positive and they never change even though the patient gets better or is treated. Same can be said for ANCA. In large scale studies, ANCA following ANCA levels has never panned out to be a good biomarker for ANCA associated vasculitis. However, when you look at the data, it does seem that in some patients it is predictive. And so therefore, I think from the outset you should be doing serial ANCA levels and seeing what happens when you treat the patient, when the patient gets better.

Do ANCA levels get better? And if they do, then I think you've got a really good tool that will maybe be predictive for you in following patients over time. Other than that, you know, I think that you're left looking at the end organ damage and the assessment of that, whether it's ENT, respiratory with chest X rays and CTs periodically, or renal function assessments, including blood pressure urinalysis and renal testing for GFR. That's it for ANCA associated vasculitis. Lastly, and maybe most problematically is large vessel vasculitis.

Giant cell arteritis and Takayasu's arteritis leading the way. And I think that you, obviously are going to rely on signs and symptoms, clinical assessment, and SED rate and CRP here might be very, very effective, as a tool looking for response to therapy or the potential for future flare. I think the real issue is has to do with whether or not you use other imaging or looking for end organ tissue ischemia. So if they've got GCA and they've lost their vision, you want to make sure they don't lose the other eye or there's no worsening of vision. And so you do your clinical assessments, you'll do your SED rate and CRP, but do you do anything more?

You don't do serial biopsies. If you believe in the data about ultrasound and the halo sign and following and you're good at that, congratulations. Most of us are not, most of us don't have that tool available to us. I think what you need to know is in GCA, ten percent of patients will have either aortic involvement or involvement of extracranial arteries like the subclavian or axillary. In those people, serial assessments by MRA may be necessary along with blood pressure assessments in all four extremities should be often done when you've proven it's beyond the ophthalmic artery or the ciliary artery that would cause blindness and those sort of manifestations.

Takayasu's is different. It doesn't involve the same vessels as you'd have in GCA. They have more peripheral vessels. They aortic arch, yes, but going out to the periphery and there again, it's clinical assessment, signs and symptoms. It's going to be labs, which are often helpful.

It's gonna be blood pressure, again, in all four extremities, I think would be paramount to the assessment of those patients. And then a vascular assessment, carotid arteries, brachial arteries, femoral arteries, for strength of pulse and whether or not they have bruits and recording that serially. I would also say that in patients with Takayasu's and or GCA with extra cranial artery large vessel involvement, you can choose between doing MRA and PET scans. PET scans are great for disease activity, but they happen to be very expensive and not generally available. MRAs are good at defining the extent of disease or the development of new disease and can be done serially, God helping the insurance company will pay for it.

Anyway, that's my assessment and management of patients with vasculitis of different sizes. I'll close with a note about our program at RheumNow Live on Saturday the fourteenth as we do on every day of the meeting. We have these TED talks. We call them step talks. Fifteen minute talks meant to be inspirational or encapsulations of new thoughts.

We got a session on Saturday morning that's just fabulous. Three major leaders from the European Union, Gert Burmester on the future of rheumatology, Robert Landaway on are we treating early arthritis correctly or not, and then the godfather of treat to target, Joseph Smolin's gonna say ten years later, are we doing this right or not on treat to target? It's an exciting program. Check it out at roomnow.live.