Is the unlucky 30% of "non-responders" a reality?

General Medications
1

Hi folks,

I had a visit with my doc yesterday. He seems like a great doctor compared to the other two rheumatologists in the past 15 years that put me off by mis or underdiagnosing PsA. But I digresss...

Back to the point and a couple of questions.

I am on my third biologic. I had an allergic reaction to the first one (Remicade) no results with the second one (Orencia) and I am now about 8 weeks into Humira. No response. I might even be worse.

Doc told me that we should give the Humira about 4 more weeks, and that the next thing he would recommend is Stelara or Simponi Aria. He added that about 30% of people do not respond to anything.

I'm also on 15 mg of methotrexate per week and 5 mg prednisone per day.

I don't want to jump the gun and loose hope, but I want to be realistic. If none of these drugs work for me, what in the world does one do ? Wait for the next drug to come down the pike and just keep trying?

When you have the spondy phenotype, does it do any good to keep taking something that doesn't seem to be helping? If you don't feel better, is the med still keeping the disease at bay, or is PsA just flaming out of control either way?

Thanks in advance for any studies, thoughts, links or anecdotes you can share.

2

The only thought I have, MimiB, is “great questions”!

3

Yes, very good questions MimiB, and ones that I am beginning to ask as well because nothing has worked for me. Yet!

It's great that you are being escalated through the biologics. Here in the UK the guidelines which govern the way PsA is treated say you only get one shot at a biologic, I've tried and failed to respond to Humira. To get funding for a second anti-TNF the bean-counters and NHS politicians have to review your case and find you worthy of the financial investment.

I think we all have to keep the hope that further breakthroughs will be made in understanding and treating PsA and that we will all benefit in the future even if current medications don't work for us. I try to remind myself that when there is nothing left there is always hope, but only when there is no hope, there is nothing left!

4

I failed Enbrel. Now on humira 3 weeks. No improvement yet. We have no choice. Must keeping waiting and hoping for new, better therapy.

5

I had not heard about this 30% and am pleased that my Rheumatologist keeps saying we WILL find something that works for you. I'm on my 6th drug-Enbrel. I failed on Humira and also had an allergic reaction to Remicade. My Rheumatologist keeps saying there are LOTS of other options. I'm trying to be optimistic. I know and feel your frustration...and fear, and pain. Here's hoping we all find something that works for us!

6

Please hang in there! I have had PSA since 1977 and I have been on every kind of treatment you can think of for Psoriasis and Psoriatic Arthritis. I have been taking methotrexate since 1987. I have had times where the meds have worked and other times where I have gone through all the biologics with no avail. I recently completed that cycle and asked my doctor if I could try Enbrel again since it worked so well the first time in 2000 he was weary but also knew that we had exhausted all of the other current drugs available at this time. To his and my surprise it gave me some relief not the fabulous omg I am cured relief that I achieved the first time but I am thankful for my regained mobility. I also inject my methotrexate now instead of taking it orally. I think this helps! I also think that I was very lucky to have had the same caring, compassionate and totally knowledgeable Rheumatoligist from 1977 to 2013. He has recently retired but left me in the hands of one of his partners. I don''t know what the future holds but I know that we can never give up trying and just focusing on the next step. I marvel at the amount of news our disease gets. My disease started in high school and I had no idea anyone else was suffering with the pain of the arthritis and the shame of the psoriasis. I am so thankful that this disease is out there and there are blogs like this.

7

You and your Rheumy sound like a good team. Congrats! There are all kinds of DMARDS and NSAIDS, and Anti-TNF meds that might, possible work in combination with each other. I keep telling myself (and everyone else who will listen) that each person's body and medication reactions/response is different. I know that I've been on Humira, Enbrel, and Remicaide all with and without MTX. So far I've had the best results with Remicaide, but was only on it for 5 months before the cost of infusion made me stop and go back on the Enbrel. I am also flaring out of control. So now I am off the Enbrel and waiting to start Remicaide again with MTX. I am also taking Diclofenac (NSAID) and Sulfasalazine (DMARD) and Dexamethazone (7 days full pill, 7 days 1/2 pill) which has fewer nasty side effects for me than Prednisone. I still haven't found that magic mix of meds that will calm the flare, but I remain hopeful.

You may want to do some research about all the meds that are available, and then take a list of things you want to try to your next appointment. I know I am guilty of letting the Rheumy guide my treatment because it was easier, but I've lately started researching symptoms, meds, etc and the doc has agreed to let me try different mixes of things every 6 months - 1 year (depending on the med) until we find something or a mix of somethings that will let me get my life back.

Good luck to you!

8

hello
i have found that if i cut down on sugar 50% the pain is less. it seems like sugar aggravates the inflammation.

i take humira once a month now. i was on it every other week for a year but did not see a huge difference. honestly it works better for my skin than pain. also i stopped methotrexate

because i also have fibromyalgia i take Lyrica but the jury is still out as i dont know if that works.

psoriatic arthirtis is the strangest disease as some days the pain feels overwhelming and fluish and other days i am better. one thing is for sure... i am fatigued and must take a nap each day.

i do believe that diet is a part of this but its hard to change when you are in your 50's. but i am trying

thanks

steven

los angeles

9

I hadn't heard that 30% don't respond to anything, but have read that only 50% or so respond to any one biologic. Depressing, isn't it? As expensive and hard to get as they are, you'd think they would have you up and dancing fifteen minutes after the first dose.

After I struck out on my second, my doc did say that there are several promising new PsA drugs in the pipeline. Hope she's right.

10

I have had extensive food allergy testing done because I was allergic to the world and about to have to go on a tube feeding product for any nutrition at all. In the course of the testing I was also tested for chemical reactions. They uncovered some pretty strange things. Because of my background in foods, I was able to take the info I was given and add to it. We now know that some specific foods to which I showed allergic reaction also trigger whopping flares of psoriasis, PsA and fibro in me, so I do not eat them at all. (AT ALL!). Easy to learn once you have a few less pain days and finally feel the difference. Topping the list are pepper (the kind you sprinkle on food, not vegetable type), fresh tomato (I can barely tolerate tomato that's been cooked into oblivion), mushrooms, orange, fish and egg. On some of these, the inflammation is evident as I appear to have burns and the red skin is hot to the touch. (I have literally burned and peeled before knowing what was causing this). On others you can set an alarm almost for which day the symptoms are going to hit. It's so predictable that my then 6 year old niece knew the schedule. I can get away with a small amt of egg occasionally and a small amt of very cooked tomato occasionally, but never escape consequences completely. Mushrooms will always, without fail, bring on a headache that is fairly significant but with which I can still function. Fish brings a migraine that is unbearable, and black pepper, cloves and cinnamon all but kill me off for many days with muscle spasms and weakness that are really, really awful. None of them is worth it. All of them have a gut component as well. All of them make my pain skyrocket. Learning to cook without using tomato has proven the most difficult but I can make good food again without it in any form.

All of the conventional wisdom about nightshades in not proved out in me. I have no symptoms with potatoes for example.

One of the chems to which I overreact is formaldehyde. Few people realize that both mushrooms and black pepper are loaded with it. So it makes sense I'd have trouble with them. I avoid both like the plague, for example no seasoning on an In and Out Burger or fries-- The seasoning has pepper in it. It's taken a lot of study. Thank heavens for my profession and background or I surely would never have connected the dots. I barely did anyway. So point of this diatribe is to say absolutely there is a connection between diet and pain, but I think it's highly individualized. Much of my continuing education for my profession now focuses on this area. There is far too little out there to learn from and far too little credible work published. I latch on to anything credible and study it and apply it. All of my continuing education for my profession is now focused on this area. (And I take Humira, and Mtrx and Ketoprofen 200 mg). I am often discouraged and fight that mightily. Maybe with what all of us learn will in time provide good data for others who will follow.

If there's a food discussion, I'll copy this there if wanted.

11

Pollyanna,

A thread about this might go well in the “Complementary Therapies” section. Go to Discussions, and then scroll down. You can start it there.




Pollyana said:

>If there’s a food discussion, I’ll copy this there if wanted.

12

Hi mimiB!

Like you my first reaction to Humira was "huh?" It has taken four months for me to notice much improvement (whereas with Enbrel the improvement happened immediately). This winter break from school and work I undertook a little home improvement project. I only mention this because for seven days I did something strenuous, whether it was spackling holes, priming and painting trim pieces and paneling, using a drill and a screw gun, painting walls and ceilings, etc. etc. etc. I tell you this not because I'm angling for my own show on HGTV, but that even though I had some pain and swelling after being so active, I had the energy to do this work every single day. Without fail. So, I wasn't sure that Humira was really doing much of anything, but now I know it has to be doing something positive for me to have so much more energy. It isn't as good as Enbrel was for me at first, but it is good enough. I can manage any nightly pain and swelling with NSAIDs, but there is nothing I could do if I were chronically fatigued (like I was before I went on Humira after being off all meds for 8 weeks).

I hope my little explanation convinces you to keep on with the Humira. It was such an incremental change that it was hard to know that it was happening at all. Good luck to you!

13

Thanks for everyone's replies. It is very encouraging to hear that some of you were late responders to Humira. I shall keep trying. Right now I am reducing my prednisone from 5 to 2.5 as an experiment ( with my docs approval, of course ) This is the second day, and man, do I notice a difference. But I am going to try and see if I can manage on it and go down from there. I would really like to get off this stuff ! Doc said if it got unbearable to go back to 5 mg for now and wait to see if the Humira is going to kick in. It's a cold rainy day, so I plan to stay in and make some art today, read and catch up on "Keeping Up Appearances" on Youtube. It makes me laugh.

14

For many reasons I have avoided this discussion if for no other reason than I don't understand what the premise is or what a non-responder is. Mimi's doc isn't here to explain what he meant.

Here is a very recent study: http://arthritis-research.com/content/13/1/R25

Its a highly technical study from a statistical standpoint, but in any event, it concludes: "For patients with prior exposure to TNF-α inhibitors, the likelihood of response to subsequent treatment with biologic agents declines with the increasing number of previous treatments with TNF-α inhibitors."

If you track it following the formula they used under efficacy, you come up closer to amuch higher number responding (eventually) to some combination. Put simply somewhere around 60% respond to their first (leaving 40% who didn't about 40 respond to the second etc etc coming up with no where NEAR 30% who never respond. Here is a more plain language explanation Format: DOC Size: 206KB Download file granted 90% may be a stretch as there aren't enough drugs yet to get to a complete regression.

The other problem is that statistically its hard eliminate the outliers. The fact is 50% of non-responders discontinue the drug for reasons OTHER that whether it works or not........... Under stand response is considered a 50% improvement in symptoms (it only takes a 20% improvement to be an approved treatment) I am about to make a statement that will piss off many. But understand some people will never accept improvement as a positive outcome.

The fact is we have far too many people for whom improvement isn't an option. They are and will remain hysterical about their disease. The idea of living a mostly normal life with pain and symptoms is un-acceptable. Even if the alternative is sitting their ass until they die becoming obese, isolated, depressed, and generally removed from society NO treatment will be "succesful" unless it restores them to their pre-PsA state. I got news for them , you are screwed. It ain't gonna happen. These people invariably end up surrendering control of their lives to "pain management" docs who simply blast them into an outter world with narcotics.

The simple fact is fewer than 10% ever become incapacitated by this disease alone.

15


Thank you, Lamb. To clarify, I seem to remember my doc saying that a non response most likely had to do with genetics, but I did not ask for a technical explanation of what he meant by that,

In my case, the first anti TNF treatment, Remicaide, was discontinued due to an allergic reaction but I did notice some improvement of symptoms after the second infusion. The second biologic I tried was Orencia, which is not a TNF inhibitor. I noticed absolutely no improvement, on it, not even a hint. Ditto with Humira so far, but I plan to keep trying, as long as I tolerate it and have no adverse events.

So, can you break this down for me ? Are you saying that if you have 20-50% improvement with a biologic that is the best you can hope for, and as long as you are tolerating it you should stick with it? What about if you just maintain, or notice no improvement, but tolerate the drug? Is it still helping?


tntlamb said:

For many reasons I have avoided this discussion if for no other reason than I don't understand what the premise is or what a non-responder is. Mimi's doc isn't here to explain what he meant.

Here is a very recent study: http://arthritis-research.com/content/13/1/R25

Its a highly technical study from a statistical standpoint, but in any event, it concludes: "For patients with prior exposure to TNF-α inhibitors, the likelihood of response to subsequent treatment with biologic agents declines with the increasing number of previous treatments with TNF-α inhibitors."

If you track it following the formula they used under efficacy, you come up closer to amuch higher number responding (eventually) to some combination. Put simply somewhere around 60% respond to their first (leaving 40% who didn't about 40 respond to the second etc etc coming up with no where NEAR 30% who never respond. Here is a more plain language explanation Format: DOC Size: 206KB Download file granted 90% may be a stretch as there aren't enough drugs yet to get to a complete regression.

The other problem is that statistically its hard eliminate the outliers. The fact is 50% of non-responders discontinue the drug for reasons OTHER that whether it works or not........... Under stand response is considered a 50% improvement in symptoms (it only takes a 20% improvement to be an approved treatment) I am about to make a statement that will piss off many. But understand some people will never accept improvement as a positive outcome.

The fact is we have far too many people for whom improvement isn't an option. They are and will remain hysterical about their disease. The idea of living a mostly normal life with pain and symptoms is un-acceptable. Even if the alternative is sitting their ass until they die becoming obese, isolated, depressed, and generally removed from society NO treatment will be "succesful" unless it restores them to their pre-PsA state. I got news for them , you are screwed. It ain't gonna happen. These people invariably end up surrendering control of their lives to "pain management" docs who simply blast them into an outter world with narcotics.

The simple fact is fewer than 10% ever become incapacitated by this disease alone.

16

I did also remember seeing this statement on Rheumatoid Arthritis warrior's page :

http://rawarrior.com/efficacy-of-xeljanz-biologics-dmards-in-rheumatoid-disease/

"The efficacy data with Xeljanz differ among their various trials, but they are similar. And response levels are comparable to those of Biologics, using ACR20, ACR50, and ACR70. Three years ago on RAW, we discussed some comparisons of efficacy of Biologics, according to a Cochrane review of 31 studies of ACR50 and Danish study of ACR70. Looking at trial data and comparison studies, on average, about 34% are non-responders, which means they do not meet the primary endpoint of ACR20 (an assessment of 20% improvement according to specific measures of disease activity). The remaining 66%, considered responders, are divided between ACR20, ACR50, and ACR70. On average, 20% or fewer people experience 70 percent improvement, and about 29% reach ACR20 only. The remainder are ACR50 only."

And this statement:

"

Most of what people know about treatments for Rheumatoid Disease has been communicated by pharmaceutical companies through drug reps, or in press releases or direct to consumer advertisements. The experiences of patients, and the results of clinical trials present a different impression.

There is wide variation in response rates to current Rheumatoid Arthritis treatments. Medications are highly effective at reducing symptoms or slowing progression of damage in a minority of patients with moderate to severe disease who are prescribed disease-modifying anti-rheumatic drugs (DMARDs) or Biologics, but a majority experience limited response (about one-third are non-responders and nearly 30% have only twenty percent improvement)."

from this page: http://rawarrior.com/levels-of-treatment-response-in-rheumatoid-arthritis/

And there is this, a urine test which may predict who will respond favorably to TNF treatment.

Abstract

OBJECTIVE:

Anti-tumor necrosis factor (anti-TNF) therapies are highly effective in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), but a significant number of patients exhibit only a partial or no therapeutic response. Inflammation alters local and systemic metabolism, and TNF plays a role in this. We undertook this study to determine if the patient's metabolic fingerprint prior to therapy could predict responses to anti-TNF agents.

http://www.ncbi.nlm.nih.gov/pubmed/23460124

17

You have some good stuff there. Thery are doing some great work with the testing. I suspect it'll not be much longer until ee can match bios.

It appears your doc is going by group. I'd ask why he didn't go to Simponi, or wasn't he aware you were feeling effect from the Remi? As you are aware simponi and remi are 1st cousins.

18

I do think he mentioned Simponi Aria, and that it might be an option. I did mention to him that I had some relief from Remicade before I had the adverse reaction to it. It's always an adventure, isn't it ?

19

We are PsA twins! I was dx in 1980. Also been on everything. Currently trying Stelara, just approved for PsA a few months ago. I agree, there is always something new, or some new combination to try.

mamartin1014 said:

Please hang in there! I have had PSA since 1977 and I have been on every kind of treatment you can think of for Psoriasis and Psoriatic Arthritis.

20

I also had a reaction to Remicade. Dr. told me today he was moving me to Cimzia. I heard him say in a PsA Conference that they never run out of Rx options. The same way that I have to switch antihistamines when my body gets used to the same one, I stay of it for a while and get back to it and it has some effect again.

Like everything else in life, once you have a disease, you have it. Medications can only attempt to CONTROL it to a certain degree only, but diseases have this downfall of unavoidably running their course. A very sweet friend of mine died of MS. No matter how much money or treatments were done, she died anyway. Now, that is a fact of life. We can go cursing our luck or we can go enjoying and thanking God for every blessing and new day we see. Quoting my dr., "Staying positive helps the outcome of the treatment".

Pain? My dr. and I are working on it. It CAN be diminished, but will not go away. I have been building a better tolerance to pain. This helps. When not, my doc will hear my scream!