Category: medications

DeepCure’s AI Platform Creates Novel Brd4 Inhibitor

Posted on by Grayson

The following is an excerpt of an article on Drug Discovery Trends, dated 9/9/2024:

The company’s first AI-generated drug candidate, DC-9476, a selective Brd4 BD2 inhibitor, embodies this approach, showing promise in preclinical models of autoimmune diseases like rheumatoid arthritis (RA) and Still’s disease. In RA models, DC-9476 demonstrated superior efficacy compared to standard treatments, including TNF-alpha inhibitors, IL-6 inhibitors, and the JAK inhibitor tofacitinib. DeepCure recently announced a collaboration with the Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM) to test DC-9476 in RA.

Read the full article here

Tocilizumab-induced Hypofibrinogenemia in SJIA Patients

Posted on by Grayson

Tocilizumab (or Actemra) is an IL-6 inhibitor commonly used to treat SJIA and other types of autoimmune and autoinflammatory arthritis. As with all medications, we know that tocilizumab has a variety of side effects. These include lowering blood cell counts, making it easier to catch upper respiratory infections, and allergic reactions (in extreme cases).

Before we dig into the latest study on tocilizumab and hypofibrinogenemia, what in the world is hypofibrinogenemia?

Fibrinogen is a protein that is created in the liver. The body uses this, along with other proteins, to form blood clots and stop bleeding. Depending on how often you’ve run into issues with this protein, you may also know it as Coagulation Factor 1. Blood tests like Factor 1 and serum fibrinogen help monitor the level of fibrinogen in the body, either taking a look at how well the protein is working or what level of the protein is in your blood. Medscape has a really deep dive for those interested.

Generally speaking, hypofibrinogenemia is a rare, inherited blood disorder. They’ve found some responsible chromosomes for this. What hypofibrinogenemia does is present as an abnormality in the quality of fibrinogen, and so it causes issues with blood clotting. Folks with this condition might have things like GI bleeding, excess bleeding following surgeries or procedures, or even events like miscarriages. This can often present as bloody noses that take a long time or are difficult to stop. People may require plasma infusions all the way up to a liver transplant, depending on the severity of this condition. They also have to avoid medications such as NSAIDs that tend to alter bleeding and platelets.

Now, what does this have to do with tocilizumab?

According to a study in Nature, tocilizumab can cause hypofibrinogenemia in SJIA patients. They found that 76.47% of SJIA patients receiving tocilizumab had hypofibrinogenemia. The patients with this condition had a variety of disease activity, including inactive disease, and some were on both methotrexate and prednisone as well. However, those medications were determined to have negligible effects on developing hypofibrinogenemia.

It’s important to note that there was a pretty small number of patients retroactively studied. Around 60% of these patients had no specific symptoms, but some symptoms included bleeding gums and increased bruising. Only one patient studied struggled with nose bleeds.

Why is this happening?

IL-1, IL-6, and TNF all affect fibrinogen. IL-1 and TNF negatively affect it, meaning those of us on IL-1 or TNF inhibitors may receive a boost in our fibrinogen levels due to lower IL-1 and TNF levels. Makes sense, right? Well, IL-6 positively affects fibrinogen. That means IL-6 inhibitors like tocilizumab may cause issues such as hypofibrinogenemia.

Should I be worried?

Worried? No. Proactive? Yes.

First, some notes:

They did test these patients and found they did not have the chromosomes related to hypofibrinogenemia. That means this may not have been an inherited condition for them OR there may be a link between SJIA and this condition that we’re unaware of at the moment.

The researchers admit that this retroactive study with a small number of patients means not enough overall data was collected, so a lot more research needs to be done. They also wondered if there’s a difference for adults versus children when it comes to this, especially since hypofibrinogenemia set in after 1-4 doses of tocilizumab in pediatric patients.

Now, as far as being proactive:

If you or your child is on tocilizumab, it’s worth keeping track of symptoms that may be related – nose bleeds, increased bruising, etc. These could be explained by anemia, which needs to be treated, too. However, it’s worth sharing this study with your rheumatologist to see if they can test your fibrinogen levels if/when they test for anemia as well.

You can read the full study here.

Celltrion Unveils Phase 1 Clinical Data of Actemra Biosimilar at EULAR

Posted on by Grayson

The following are excerpts from The Korea Economic Daily dated May, 31, 2023:

South Korean biosimilar giant Celltrion Inc. revealed on Wednesday the highly anticipated clinical phase 1 data for its Actemra biosimilar, CT-P47, at the 2023 European Congress of Rheumatology (2023 EULAR) conference.

The clinical data for CT-P47 was made available online by Celltrion, following a phase 1 study involving 318 health South Korean subjects. The company announced that it had successfully demonstrated pharmacodynamic (PK) equivalence and safety comparable to the original drug.

Click here to learn more.

First-line use of biologics may lead to favorable outcomes in sJIA

Posted on by Grayson

The following is an article released May 15, 2023, by Contemporary Pediatrics:

A study in patients with new-onset systemic juvenile idiopathic arthritis (sJIA) found most patients treated with biologics had desirable short-term clinical outcomes combined with decreased use of glucocorticoids (GCs).

The 73 patients in the study, who were enrolled at numerous sites, were aged 6 months to 18 years at disease onset and had a fever for at least 2 weeks, arthritis in 1 or more joints for at least 10 days, a rash, and generalized lymphadenopathy, among other symptoms, and had received initial treatment with biologics or nonbiologic GCs. Participants were treated according to 1 of 4 plans chosen by their physicians, which included 2 biologics (interleukin [IL]-1i and IL-6i, both with or without GC) and 2 nonbiologics (methotrexate with or without GC and GC alone); 63 patients (86%) were enrolled in the biologic treatments and 10 (14%) in the nonbiologics. Investigators collected clinical data at baseline and 2 weeks as well as at 1, 3, 6, 9, and 12 months following enrollment.

In choosing a treatment plan, many health care providers reported that they initiate treatment of sJIA with a biologic agent most of the time. They said this is because of the likelihood of the biologic’s effectiveness for systemic features, minimizing systemic glucocorticoids, and the possibility of effectiveness for arthritis. Of the 10 clinical sites that enrolled 3 or more patients, 8 sites assigned all their patients to the biologics.

At 9 months, 57% of patients achieved the primary outcome of clinical inactive disease (CID) without current GC use and 75% had a clinical juvenile arthritis disease activity score at or below 2.5 with no fever and no current GC use. Patients in the biologic and nonbiologic groups had similar outcomes, but 4 of the 6 patients evaluated for CID in the nonbiologic group had initiated biologics during the study. Outcomes at 12 months were similar to those at 9 months. Of the patients receiving biologics who subsequently started methotrexate, 1 of 6 had CID without concurrent GC use at 9 months.

Beukelman T, Tomlinson G, Nigrovic PA, et al. First-line options for systemic juvenile idiopathic arthritis treatment: an observational study of Childhood Arthritis and Rheumatology Research Alliance consensus treatment plans. Pediatr Rheumatol Online J. 2022;20(1):113. doi:10.1186/s12969-022-00768-6

If you want to read the full journal article cited above, you can do so here.

"Things to ask before okaying medication changes" with a photo of a provider discussing a topic with two people

Evaluating Medication Changes

Posted on by Grayson

Before making any changes to your medication regimen, it’s important to carefully consider the possible risks and benefits. Your doctor may recommend a medication change to better manage your symptoms or improve the effectiveness of your treatment. However, it’s crucial to fully understand why the change is being made and what the potential side effects or interactions may be.

In this article, I’ll outline some of the key things you should ask before okaying medication changes, including understanding the risks and benefits, discussing alternatives, and monitoring your health. By being an active participant in your healthcare decisions, you can make informed choices about your medication and ensure the best possible outcome for your health.

Continue reading “Evaluating Medication Changes” →

And Now, My Liver

Posted on by Grayson

A few things have happened since my last health update, so I figured a new update was due.

Swallowing

While I know my rheumy put in a referral for speech pathology to help with my esophageal dysmotility, I’ve not been contacted yet. I’m sure that my swallowing issues are towards the end of their priority list, and that’s fine.

In the meantime, I’ve been relying heavily on plastic straws. The other options just do not work for me. That’s especially true when my dishwasher keeps running into rust problems. I don’t trust it to clean any kind of straw, and I don’t have the hand dexterity lately to wash them by hand. It’s an important part of why plastic straws exist – and why they shouldn’t be banned.

People who can drink without straws should, but don’t ban them. You’re losing any potential business from a wide variety of people.

GI

I’ve been keeping to my low FODMAP diet… for the most part.

Because of that, I’ve been able to recognize some other things that exacerbate my IBS. While I might not necessarily cut things like coffee completely out of my diet, I also know to expect – and prepare for – the end result. If I know I need coffee, I can premedicate with an anti-diarrheal, too, to help limit the intensity.

My follow-up is in October. I’ll likely go through with the gastroparesis study. Now that I’m not dealing with exacerbated IBS every single day, I am noticing how long it takes my body to process things… and it’s still too long.

Cardiology

My Holter monitor came back fine.

I’m floored, honestly. I have no idea how that was the case, but I also know a lot of heart issues can’t be found with that monitor. My rheumy has offered to pass me along to cardiology for a full workup.

I should take her up on it. I know I should. For some reason, though, I’m just pushing it off because, honestly, it scares the shit out of me.

Migraine

Since changing from estrogen-filled birth control pills to an IUD, my migraines has drastically decreased.

Over the last 20 days, I’ve only had 3 migraine-related issues. Two of those were full-on migraines while the other one was medicating early to stop a migraine.

MCAS

I’ve finally got a good medication routine down that stops most of the reactions I was having. Thanks to fellow MCAS patients, I’ve been able to figure out many of the things I react to. Sadly, that means limiting more dyes than I would’ve liked.

At the same time, can I live without wildberry skittles? Yes, yes I can.

Trigger Point Injections

I’ve been getting these for a while now.

I was terrified when I started, but they’ve really helped. As odd as it is to say, I’ve grown to appreciate needles in my head, neck, shoulders, and back.

I had a round of these last week and we did our fewest number of injections yet! It only took four shots to give me relief.

That’s incredibly amazing.

Because of that, we’ve been able to push off the next set from every four weeks to every six weeks… which means I get another round on Halloween!

*imagine spooky noises here*

And Now, My Liver

I stopped by the lab and got blood drawn after my injections last week. My CBC was great, but… my liver didn’t look good.

My AST was 42, when the normal range is up to 36. My ALT? 59, well above the 0-33 normal range.

While we’re not sure why this has happened, the Zyrtec I’m using to take care of my MCAS – up to 40 mg/day – can cause ‘abnormal hepatic function.’ So can my Nortriptyline, which was upped to 30 mg in June. I’m trying to only use 30 mg of Zyrtec for now and avoid using Zantac (another histamine blocker) when possible because, surprise, it can do that, too.

Rheumy has ordered another run of these labs in a month.

Time to shoot her a message about med use and a cardiology referral.

Did Methotrexate Make Me Gluten Intolerant?

Posted on by Grayson

a photo of a clear pill organizer with mostly white pills and orange-yellow ones in Friday's slot against a black table; a yellow overlay with white text: " Did methotrexate make me gluten intolerant? Not Standing Still's Disease "

When I started methotrexate in late 2010, it was rough. I started on the pills and then discontinued them, moving on to biologics. After switching to a new rheumatologist a year later, I tried it again – this time as an injection in conjunction with Enbrel.

About this time is when I noticed that anything containing gluten made me incredibly sick. We ran a Celiac blood test but, as I wasn’t eating gluten, it came back inconclusive.

Since the only treatment for Celiac disease is to maintain a gluten-free diet, I’ve maintained that since late 2012. It’s not always been easy. The advancements in gluten-free products have made it easier. I’ve learned a lot of cool cooking and baking tricks along the way. I have to work more for my food, and that’s a good thing.

Throughout the years, I’ve wondered many things about my inability to eat gluten. Why did it come on so suddenly? Is there a reason it continues to last? Why did it come on when it did?

I recently came across a few journal articles that might shed light on that.

Apparently, there have been cases where gluten intolerance-like behavior has come on as a result of methotrexate. For most patients, this has calmed down after following a gluten-free diet and discontinuing the medication. These patients were then able to restart consuming gluten.

But I wonder – what is it that these patients have received as far as care that has led to this recovery? Are there patients for whom this never cleared up?

I survived on bread for the longest time. My go-to foods were sandwiches, bagels, and garlic bread. From 2010-2012, I practically lived on pop-tarts and on-the-go pastries or protein bars. What else could have changed during that time period to trigger a gluten issue?

I just don’t know.

If you’ve dealt with gluten intolerance after being on methotrexate, has it cleared up? Is it situational or stress-related? I’ love to hear from you.

Nortriptyline, Day 9 & Spine PT

Posted on by Grayson
photo of a lightbulb hanging down with a white line down the right side and a black box on the bottom with white text: "Nortriptyline, Day 9 & Spine PT" and "Not Standing Still's Disease"
First, the nortriptyline update: The nausea is still strong. I spent all morning yesterday running errands post-doc appt while trying not to throw up. I’m still dealing with headaches – well, until this morning, because I finally got some real sleep.
My appointment yesterday was with my GP to talk about my bulging disc. She’s sending me for spine PT which starts on the 18th. If that doesn’t help in the next 4-6 weeks, we’ll talk again and consult someone about what else we might be able to do before moving to surgery. This means I’ll be doing pelvic floor PT and spinal PT at the same time.
She also gave me a new script for cyclobenzaprine. I used to take that regularly and then my former rheumy stopped prescribing it, and the newer one didn’t want to.
Of course, I had to sit through the ‘losing weight helps’ speech at my appointment. I’m so tired of hearing that, especially as I’m saying I can barely sleep, walk, and do anything. Like, that’s not the time to lecture me on my weight.
The cyclobenzaprine, even at a half dose, helped immensely. I was able to sleep last night, in my bed. It’s been weeks since I woke up in my bed at a normal time.
I even slept another few hours this morning.
All that said, my headache/migraine is easing up with the sleep. My back pain is becoming more prominent, though. I’m not too worried about that for now, especially since I only did a small dose of my cyclobenzaprine.
Maybe now that I’m able to sleep more, the nortriptyline will start working.

 

Nortriptyline, Day 5

Posted on by Grayson
photo of wooden planks with mint green thin bars at top and bottom - in the bottom bar white text "Not Standing Still's Disease" - at middle a pinkish thicker bar with white text 'Nortriptyline, Day 5"
Last night was my fifth dose of nortriptyline. As noted previously, there isn’t expected to be much improvement until later on once the medication has been able to build up in the system.
The nausea is easing up a tad, though not much. It seems to be more recurring than constant which is an improvement. That said, after dinner last night, I nearly threw up everywhere.
I put the other half of my pizza in the fridge and decided it was a good time to get out my daily Kineret shot so that it could warm up. It makes the shot hurt a lot less and I wind up with fewer bruises and marks that way. We keep my meds in what would be the meat drawer in a normal household. This way they’re more insulated if the power were to go out, but they’re also always in the same spot and don’t get crushed if I drop a Coke can, etc.
I bent down, took out the box, grabbed a shot, and set it on the counter. As I bent back down to put the box back, I got nauseous. As I came back up – something that’s been giving me trouble lately anyway – I nearly threw up. Twice.
After a mad dash to the bathroom and sitting in front of the toilet for about ten minutes, the feeling passed and I was okay.
I definitely felt like I was on the verge of throwing up all night, though.
Whether or not this is med-related, I don’t know. I do know that my nausea has generally increased due to this med, but also that my GI tract isn’t processing food the right way. Since I had just eaten a real meal, it could be more due to that than the meds.
From a migraine perspective, I haven’t really noticed much improvement. I’m still waking up with some headache that may or may not improve after taking my morning meds and stretching.
I do feel like my mood has improved slightly. I can’t say whether that’s from the meds, the pain easing up, or the long weekend and spending more time with T.
On another note, my back pain has eased up a bit as well. I believe the EMG and nerve conduction study amplified my pain for a few days, a combination of laying on an uncomfortable exam bed for over an hour and my already angry nerves being zapped.
That said, I’ve also been moving in ways that are within limits my body is currently setting instead of trying to push myself so much. I could see that helping as well.

 

Nortriptyline, Day 1

Posted on by Grayson
square photo with thicker outline in black on the left side and white on the right side; pic in the middle is capsules in a pill bottle top, but distorted and unfocused; white text towards top middle says "Nortriptyline, Day 1" and bottom middle says "not standing still's disease"
As I brought up yesterday, my neurologist started me on Pamelor (Nortriptyline) as a preventative for migraines. It can help others when the right dose is reached. The pharmacist told me it could take over a month for this medication to start working. To help others, I wanted to document how this process goes. This won’t be a daily update, but every so often.
I wrote the post yesterday after taking this first pill. It was recommended to take it at night as it can cause drowsiness.
By the end of writing that post yesterday, that hadn’t kicked in as much as nausea had. It was really bad.
I spent time in bed, trying not to vomit.
I also couldn’t get comfortable at all. I was laying in bed and snuggling my husband while breathing like I was giving birth on top of the nausea. The pain in my lower back was so severe that I thought I was going to pass out. I should’ve said something to T, but I physically could not.
There was no way to take my attention off the pain. It was so all-consuming – far worse than it’s been recently.  That’s scary on its own. I just set up an appointment with my primary care doctor to discuss what to do with this disc after messaging back and forth with one of the nurses.
As for the nortriptyline, I have not noticed any improvements regarding my headache/migraine-topia as of yet… nor did I expect to.