Rituximab trial results for SS

[Sharon]

Unfortunate findings for SS patients:

"The B-cell depleting agent rituximab (Rituxan) was not effective in reducing fatigue and oral dryness in patients with primary Sjogren's syndrome (PSS)..."

https://www.medpagetoday.com/rheumatology/generalrheumatology/63815?utm_content=bufferf1dff&utm_medium=social&utm_source=facebook.com&utm_campaign=buffer

[gurs]

when I had this years ago I didnt notice any help with the dryness anywhere. The only positive thing was no flares and my neuro issues to seem to improve as well. My hair got better too.

Im supposed to try this again in 2 weeks if all goes well. Still debating.

Gursie

[Jasper]

I put little faith in many of the trial results. Most of the trials I have read are flawed, either in their design or their primary end points. One has to read the entire trial to really get at what was actually found as opposed to just the end points, which are frequently flawed.

The longest Rituximab trial, which lasted 120 weeks weeks, clearly showed excellent results in terms of improvement in fatigue and other Sjogren's symptoms.

In addition, I have experienced vast improvement in fatigue levels and most other Sjogren's symptoms with Rituximab infusions. So has everyone else I know who is on Rituximab. So have all of my Rheumatologists other patients who she has placed on Rituximab.

Rituximab may not be for everyone, but it is a shame that these trials are not designed better so that those of us who do benefit from Rituximab, and we are many,  are not tossed out with the bathwater.

I think the researchers really need to design these studies better. And they need to quit focusing on dryness as the main end point in all studies. Dryness is important, but it is not the worst symptoms or the most disabling symptom. Dryness is not what is causing us to be disabled and unable to work. It is not what is causing us to have difficulty walking, thinking,  or performing day to day activities. They need to pick their study participants better so that they do not have a conglomerate of people ranging from people with basically no symptoms to those who are disabled. They cannot allow people to continue other immune modulators because doing so confounds the results. The studies need to go for 2 years or longer because normal waxing and waning of Sjogren's can confound the results. They need to measure the effects of the medications at realistic time points. In other words, don't measure the effectiveness of the  drug when they know it is wearing off. 24 weeks is not the time frame to measure the effectiveness of Rituximab. It is starting to wear off by 24 weeks. That is why it is repeated every 24 weeks. Plus, Sjogren's is not RA or Lupus or any other AI, so they need to start designing studies for Sjogren's patients, and not just model the study and the drug treatments after their models with RA and Lupus or other AIs.

You would think these researchers would get these rather basic concepts, but they don't seem to get it.

It is really very maddening and frustrating to read a flawed study that concludes that Rituximab does not benefit Sjogren's patients when those of us on the drug know with absolute certainty that Rituximab greatly benefits us.

[Sharon]

You make some excellent points Jasper and I think it's a shame Rituximab won't be officially approved for SJS
because of flawed studies. I know there are rheumatologists who have seen their SJS patients benefit and patients
who really rely on it.

I agree dryness it a problematic focus of these studies. If the patients' glands are already shot nothing will bring them back and improve the dryness. And yes, there are many other debilitating symptoms with SJS.

I'm hoping the Orencia (Abatacept) trials produce more favorable results.
We need a biological drug on label for SJS already!

[quietdynamics]

I think the author of the article could have chosen a more accurate title as the researcher states:
"However, most patients in this study, known as TRACTISS, had early disease and/or low disease activity, and "rituximab may still have a role in treating PSS patients with high levels of systemic disease activity who have failed to improve following conventional immunosuppressive therapy," the researchers wrote in Arthritis & Rheumatology."

Studies are just that.
Last sentence of this one: "A limitation of the study was the possibility that the primary endpoint may not been sufficiently sensitive "to detect clinically important changes in symptoms."

Rituximab in primary Sjögren's syndrome: a ten-year journey.
"..Because of the well-established role of B-lymphocytes in the pathogenesis of pSS, a B-cell targeting therapy may represent a new and intriguing therapeutic approach; in this context, growing evidence suggests that B-cell depletion by rituximab (RTX) is also effective in pSS. Of interest, besides clinical efficacy, RTX also showed biologic effects, consistently affecting the inflammation and the lymphoid organization that occur in target tissue. Moreover, the good results observed in the published trials after RTX treatment in pSS should represent the starting point to develop evidence-based guidelines for the use of biologic therapy in this disease."

Resistance to Rituximab Therapy and Local BAFF Overexpression in Sjögren's Syndrome-Related Myoepithelial Sialadenitis and Low-Grade Parotid B-Cell Lymphoma
* includes case study of patient with resistance to Rituximab
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2577948/

Social Security recognizes that sicca symptoms can for some indeed be disabling and prevent one from work.
"While some people with Sjogren's disorder have only mild symptoms of dry eyes and mouth that they are able to treat, others have disabling symptoms such as blurred vision; difficulty swallowing, eating, and speaking; and debilitating fatigue and joint pain."

[gurs]

Honestly, I dont pay attention to any of the studies done and results. As we know, each person is so unique...

Too bad we dont have many options to choose from regarding treatment. My main reason for Rituxan is to Try and help with
some neuro issues.

gursie

[quietdynamics]

Aetna site information regarding RTX and studies for numerous diseases including SJS
http://www.aetna.com/cpb/medical/data/300_399/0314.html

Begins with (about halfway down on my screen)
"Primary Sjögren's syndrome (pSS) is an autoimmune disorder affecting exocrine glands; however, a subgroup of pSS patients experience systemic extra-glandular involvement leading to a worsening of disease prognosis (Carubbi, et al., 2013). Current therapeutic options are mainly empiric and often translated by other autoimmune diseases. In the last few years growing evidence suggests that B-cell depletion by rituximab (RTX) is effective also in pSS. Patients with early active disease appear to be those who could benefit the most from RTX."

[Jasper]

I agree that when you actually read the studies and dissect them, it is clear that Rituximab in beneficial to Sjogren's patients. The problems are the study designs and the end points.

Unfortunately, most people, including many physicians, do not read the entire studies. They read the abstracts, which conclude that Rituximab does not benefit Sjogren's patients. They fail to see that the end points are flawed, the study was flawed, the time frames was flawed, the patient population was flawed, etc.

Then, the conclusion of each study, which is usually the title of the abstract, states that Rituximab does not benefit Sjogren's patients. 

I have read all of those studies, including every word in the actual studies (not just the abstracts), and they all clearly show that Rituximab benefits Sjogren's patients.

I am certainly not arguing with anyone on this forum. My problem is with the study design and the endpoints and the way the abstracts are then written and titled.

We need aggressive treatment and we need it now. We are just as important as people with RA who are started on aggressive treatment the second they are diagnosed. If we were started on aggressive treatment early, people would not become disabled and have to quit working. If we were treated more aggressively we would not have so many progressing symptoms.  If we were treated more aggressively, our other co-morbidities would decrease.  Yes, all of this inflammation makes us much more prone to other diseases processes such as cardiovascular disease. And, if we were treated more aggressively, the quality of our lives would be much improved.

[warmwaters]

I don't understand this study. It's a heavy gun medicine. You don't bring it out if you can control your symptoms by other means.  By the time you get to things like IVIG or Rituxan, you've done all the more "obvious" medicines.

People report much improved quality of life - I don't know how that falls into a math formula.

About the previous study where there wasn't much difference at 24 weeks - it's known that the effects diminish over time, and 6 months (i.e. 24 weeks) is when you are due to get another round of Rituxin.

Silly study.


BTW - I'm actually a Rituxin failure.  I didn't have much improvement on it. BUT, for those for whom it does work, it works very well.  So I'd like to see research into who should be using it.

[Kathy57]

This has been a fascinating thread!  You go, Jasper!  "Tell us what you REALLY think!"  Lol.   I agree that we can't really trust the "experts' on this because look how badly they have failed us all?

If they were better informed, it wouldn't take years to get a proper diagnosis!

My concern is that maybe it will be harder for a good doctor to order Rituximab for us because of the negative trial.

I know I sure would be open to trying it!  I've been going through kind of a good patch with my Sjogrens (except I've got a bad flu now).  If I start to get worse I intend to ask my Rheumatologist  about Rituxan!  I know he told me that they thought it was "the cure" but it is not.

It still means it helped - and helped a lot.

Just my feverish thoughts on the matter😉  I like you, Jasper!  We all need a little more spunk and fight in us!

Kathy

[Sharon]

I agree with everything written in this thread.
I share Kathy's concern about it getting harder to get Rituximab prescribed following the trial's negative conclusions.