Kevzara and prednisone effectivness

@jeff97 I guess it's one or the other then.

@ronludington
Maybe, maybe not. I definitely see experimentation and trials of combinations and dosages in the future. I’d like to live long enough to see progress done in safer alternative treatments. Someday maybe a way to prevent to occurrence of PMR and GCA.
Just thinking out loud this morning. Good morning.

@stonewheel

The crosstalk and "upstream" and "downstream" reactions of various cytokines gets extremely complex. My understanding is very limited. My rheumatologist says it is all an educated guess for which biologic might work or won't work. All I know is that inflammation pathways are not isolated pathways but more like a network of pathways that are interconnected.

I asked about Cosentyx once. The answer I received was Cosentyx might work because inhibiting IL-17 also decreases IL-6 levels.
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Artificial intelligence blows me aways sometimes but I like how it "simplifies" things to some degree.

"The immune system operates via interconnected signaling cascades rather than isolated pathways. IL-17A normally acts as a powerful stimulant that prompts various cell types (such as fibroblasts, endothelial cells, and keratinocytes) to produce other inflammatory mediators, prominently including IL-6, TNF-α, and chemokines. When Cosentyx targets and neutralizes IL-17A, it effectively disrupts this downstream amplification loop. Multiple clinical studies published on PubMed have confirmed that patients treated with secukinumab show a significant reduction in systemic IL-6 levels, as well as other inflammatory markers like C-reactive protein (CRP)."
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As far a taking more than one biologic is concerned it is a matter of "too much immunosuppression." Even being on prednisone in combination with a biologic can cause this. The problem is that prednisone can't be stopped very easily so the biolgic needs to be stopped.

I will defer to artificial intelligence again:

Over-immunosuppression is a primary concern when combining multiple immunomodulatory therapies, as stacking treatments can significantly elevate the risk of serious infections. Your point regarding prednisone is also clinically spot-on: because long-term prednisone suppresses the body's natural cortisol production, stopping it abruptly can trigger a dangerous adrenal crisis."

I wonder if cosentix is less risky than the kevzara. It's black box warnings are crazy.

@dadcue
Thanks.

“ As far a taking more than one biologic is concerned it is a matter of "too much immunosuppression." Even being on prednisone in combination with a biologic can cause this. The problem is that prednisone can't be stopped very easily so the biolgic needs to be stopped.”

…so, presently, it is common practice to take both, prednisone and a biologic, at the same time, for a while. And, the expectation is to stop the prednisone before stopping the biologic. We are informed that there’s a risk combining them. It’s a gamble, but necessary for some. I’ve had the low anc and low cell counts which can possibly lead to an increased risk of infection. But, data shows that is not happening too often (like a false negative or a false positive possibility on some test.) They must state it because it can possibly happen.

Inhibiting IL-17, appears that it automatically decreases IL-6 production. So, maybe a combination of Cosentix with another biologic (Actemra, Kevzara) is unnecessary.
But, on the other hand, a magical combination dosage for each individual may be just what the doctor orders.

Forgive the speculation. I was just excited to learn the good news that R&D is being done. I know the Interleukin “cross-talk” is complicated and combinations of biologics may be very complicated to get to a desired result in the interworkings. I do hope R&D is being funded to perform trials of biologic combinations.

In the meantime, I’ll keep injecting the Kevzara and tapering the prednisone.
With any luck, I’ll be off of both before Cosentix is approved for PMR.

Still, I think it is on its way and I’m excited for future patients.
(That sounded odd, but you know what I mean.)
Rock and Roll

@dadcue
Thanks.

“ As far a taking more than one biologic is concerned it is a matter of "too much immunosuppression." Even being on prednisone in combination with a biologic can cause this. The problem is that prednisone can't be stopped very easily so the biolgic needs to be stopped.”

…so, presently, it is common practice to take both, prednisone and a biologic, at the same time, for a while. And, the expectation is to stop the prednisone before stopping the biologic. We are informed that there’s a risk combining them. It’s a gamble, but necessary for some. I’ve had the low anc and low cell counts which can possibly lead to an increased risk of infection. But, data shows that is not happening too often (like a false negative or a false positive possibility on some test.) They must state it because it can possibly happen.

Inhibiting IL-17, appears that it automatically decreases IL-6 production. So, maybe a combination of Cosentix with another biologic (Actemra, Kevzara) is unnecessary.
But, on the other hand, a magical combination dosage for each individual may be just what the doctor orders.

Forgive the speculation. I was just excited to learn the good news that R&D is being done. I know the Interleukin “cross-talk” is complicated and combinations of biologics may be very complicated to get to a desired result in the interworkings. I do hope R&D is being funded to perform trials of biologic combinations.

In the meantime, I’ll keep injecting the Kevzara and tapering the prednisone.
With any luck, I’ll be off of both before Cosentix is approved for PMR.

Still, I think it is on its way and I’m excited for future patients.
(That sounded odd, but you know what I mean.)
Rock and Roll

@stonewheel

I don't know how soon it will all happen but I'm pretty sure it won't be within my lifetime. The clock is winding down for me. I like a good sports analogy. I'm just stalling and hanging on with a lead because I don't think I will win in overtime.
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It is important to know for sure if you have PMR/GCA. There is no guarantee that people are diagnosed correctly. I had to learn to accept that I had multiple autoimmune problems. Having more than one autoimmune disorder has been an eye opener for me. Actemra worked extremely well for my PMR symptoms, and got me off prednisone for the first time in decades. I think Actemra controlled my inflammation long enough so I could reduce prednisone enough to allow time for my adrenals to recover. My endocrinologist was surprised my adrenals were so resilient.

What I don't say very often is about what happened after the first time I tapered off prednisone. Within a week or two of tapering off prednisone the first time, 60 mg of prednisone was restarted because I had a massive flare of panuveitis. My rheumatologist stopped Actemra because a uveitis specialist insisted that I be started on Humira (adalimumab) which is the only systemic biologic therapy fully FDA-approved to treat non-infectious intermediate, posterior, and panuveitis.
https://my.clevelandclinic.org/health/diseases/panuveitis
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There was a lot of discussion between a rheumatolgist, an ophthalmologist, an endocrinologist and my PCP also was involved trying to decide what steps should be taken next. It was very complicated but Humira was started and prednisone was tapered lower after the panuveitis went back into remission. As I tapered my prednisone dose back to 20 mg, all the generalized body pain returned just like a flare of PMR. My endocrinologist said it wasn't be adrenal insufficiency since I was still on 20 mg of prednisone. The pain didn't get any better when I was on Humira and I was stuck on 20 mg of prednisone again.

My rheumatologist and I had a long discussion. He said it would be impossible to "adequately treat" all my autoimmune conditions with a single biologic. I was allowed pick between Actemra or Humira but not both. It seemed like if I chose Humira, I would need to remain on prednisone. I picked Actemra to the chagrin of the uveitis specialist who said it was only a matter of time until uveitis flared up again. So far, that hasn't happened and it has been 5 years since then.

My PMR pain stopped rather quickly after Actemra was restarted. From 20 mg of prednisone, I was more confident that Actemra would work the second time. I was in a hurry to get off prednisone again so I went from 20 mg back to 3 mg in just a few days so my adrenals would not be suppressed for very long. The taper I did made a mockery of tapering slowly off prednisone for PMR. My cortisol level was rechecked at 3 mg and it was still adequate so prednisone was stopped the second time.

I don't know what to make of all this except that I wish I was started on an IL-6 inhibitor sooner. I regret having been on prednisone for 12 years when adrenal supression became a big problem for me. I think people need to get off prednisone as soon as possible so their adrenal function isn't suppressed for very long.

I don't know what will eventually replace prednisone as the primary treatment for PMR/GCA but something needs to. This perspective reflects a major, ongoing shift in how the medical community approaches these inflammatory conditions according to my rheumatologist. He says the other problem is that patients are being encouraged by other patient to take prednisone forever so that needs to change to.
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Prednisone is cheap but the costs associated with long term use causes expensive health problems.
https://www.steritas.com/insights/the-not-so-hidden-costs-of-steroid-toxicity

@dadcue prednisone works great, but I'm glad to be off of it. I may have multiple issues too... but the Drs, are stuck on kevzara, maybe if they shift me to cosentix, maybe that will work better....

@ronludington
I'm extremely grateful to be off prednisone! I was glad for prednisone until an alternative was found. My rheumatologist was sorry it took so long.

Your doctors probably think that since you are off Prednisone that is good enough for now. Multiple problems is a greater challenge but getting someone off prednisone might be considered to be the biggest problem at the present time.

I understand what you are saying because my doctors don't want me to stop Actemra since it is keeping me off prednisone. My rheumatologist acknowledged that it would be "impossible" to adequately treat all of my autoimmune conditions. Actemra is doing a decent job of it so far but I still have problems. Being completely pain free and treating everything isn't my goal so I'm good enough for now too.