What You Sjo http://www.whatyousjo.com/ Sharing knowledge & hope for Sjogren's Syndrome sufferers Sun, 09 Jan 2022 18:39:42 +0000 en-US hourly 1 https://wordpress.org/?v=5.6.7 New year’s thoughts on COVID-19 and Sjogren’s http://www.whatyousjo.com/2022/01/new-years-thoughts-on-covid-19-and-sjogrens/ http://www.whatyousjo.com/2022/01/new-years-thoughts-on-covid-19-and-sjogrens/#respond Sun, 09 Jan 2022 18:10:50 +0000 http://www.whatyousjo.com/?p=485 ]]> Happy 2022 readers, and I hope you are doing well. It has been a while since my last update, but I am still here and relatively stable. Like many, I was hoping that vaccinations would allow a return to normalcy from our nearly 2 year pandemic, but with the advent of Omicron, it appears that the pandemic is not over yet. That said, I thought it would be a good time to consider what COVID means for Sjogren’s patients.

Those of us with chronic illnesses have had to endure many of the same challenges as others around the world: lockdowns, job and economic disruptions, supply chain issues, mental stress, and potentially the acute and long-term physical issues that come with getting a COVID infection. In addition, we faced some unique issues: a pointless run on hydroxychloroquine that limited supplies, overloaded medical facilities that made it hard to schedule our regular appointments, and a medical research system that shifted much of its resources towards COVID-19 and away from chronic illnesses.

As a result, there has been little research to discuss over the past year. There have, however, been a couple of positive outcomes from the pandemic for Sjogren’s patients. The first is that remote work is now mainstream, and it is easier than ever to find a job that allows one the flexibility of working from home. For those with chronic conditions that limit mobility and make commuting and moving around a workspace challenging but can still perform tasks on a computer, this opens up new potential to continue earning income.

The other positive outcome is tied with the very negative long COVID. One study found that 54% of COVID patients experience at least one symptom 6 months after infection, including 37.5% with fatigue and muscle weakness 23.8% with difficulty concentrating, and 44% with generalized functional impairments. For many Sjogren’s patients, those symptoms will sound familiar. Indeed, another study found that 50% of COVID patients had some type of autoantibodies in their bloodstream compared to 15% of controls. Interestingly, “in some people, the levels of autoantibodies were very high, close to the levels seen in autoimmune diseases.” Many Sjogren’s patients, including me, believe that our conditions have a viral or bacterial onset. Lyme disease patients sometimes develop similar chronic conditions as well.

While my heart goes out to any who have developed long COVID, the silver lining is that it is bringing increasing scrutiny to the causes of autoimmunity. Already some medical researchers are calling for resources to explore the link between COVID-19 and autoimmune conditions:

Experts expect that more than 15 million people will experience “long COVID,” a condition that is poised to be the next national health disaster, wrote the authors of a perspective paper published in The New England Journal of Medicine. Understanding this public health threat, the National Institutes of Health (NIH) is investing $470 million in researching the long-term effects of COVID-19. Research and academic institutions, like Johns Hopkins University, have also initiated long-COVID studies to understand the scale and severity of individuals experiencing long-term symptoms of COVID-19.

As millions of previously healthy individuals, particularly those with connections and wealth, succumb to long COVID, we will hopefully see significant resources shifted towards research to understand and treat the condition. Considering the evidence we already have that ties long COVID and autoimmunity together, it stands to reason that Sjogren’s patients could benefit considerably from such research.

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An annual Sjogren’s treatment update for 2020 http://www.whatyousjo.com/2020/11/an-annual-sjogrens-treatment-update-for-2020/ http://www.whatyousjo.com/2020/11/an-annual-sjogrens-treatment-update-for-2020/#respond Sun, 29 Nov 2020 23:22:06 +0000 ]]> 2020 has been a long year for everyone, and Sjogren’s patients aren’t excluded. I’ve encountered some technical difficulties with this site which delayed this post, but I believe the significant issues have been fixed.

The most unfortunate news is that the promising drug Orencia, which I wrote about previously, failed its phase 3 trial. The results were published at the start of the year. This was disheartening, as Orencia was the biologic treatment that was closest to approval; now, we are back to drugs that are 3-5 years away from potential availability.

Speaking of those drugs, however, there are some positive signs. The biologic drug iscalimab showed promise treating Sjogren’s patients in a small trial that began several years ago, though the results were just published this year:

In cohort 1, 12 patients were randomly assigned to receive either 3 mg/kg doses of iscalimab (n=8) or placebo (n=4), and in cohort 2, 32 patients were randomly assigned to receive either intravenous 10 mg/kg doses of iscalimab (n=21) or placebo (n=11). Adverse events were similar between iscalimab treatment groups and placebo groups, with adverse events occurring in all patients in cohort 1, and in 52% and 64% of the iscalimab and placebo groups, respectively, in cohort 2. Two serious adverse events were reported (one case of bacterial conjunctivitis in cohort 1 and one case of atrial fibrillation in cohort 2), which were unrelated to treatment with iscalimab. Intravenous treatment with iscalimab resulted in a mean reduction of 5·21 points (95% CI 0·96–9·46; one-sided p=0·0090) in ESSDAI score compared with placebo. There was no signficiant difference in ESSDAI score between subcutaneous iscalimab and placebo.

Another biologic by the name of seletalisib showed promise in phase two trials published in September:

Twenty-seven patients were randomized (seletalisib n = 13, placebo n = 14); 20 completed the study… a trend for improvement in ESSDAI and ESSPRI [difference vs placebo: –2.59 (95% CI: –7.30, 2.11; P=0.266) and –1.55 (95% CI: –3.39, 0.28), respectively] was observed at week 12. No significant changes were seen in saliva and tear flow. Serious adverse events (AEs) were reported in 3/13 of patients receiving seletalisib vs 1/14 for placebo and 5/13 vs 1/14 discontinued due to AEs, respectively. Serum IgM and IgG concentrations decreased in the seletalisib group vs placebo. Seletalisib demonstrated efficacy in reducing size and organisation of salivary gland inflammatory foci and in target engagement, thus reducing PI3K-mTOR signalling compared with placebo.

In addition, there was a trial of a combination therapy of two non-biologic drugs, leflunomide and hydroxychloroquine. Hydroxychloroquine (Plaquenil) is disease-modifying antirheumatic drug (DMARD) approved for Lupus and Rheumatoid arthritis. It is also a common off-label treatment for Sjogren’s patients despite its past failures in clinical trials. Leflunomide (Arava) is also a DMARD that has been approved for patients with rheumatoid arthritis. Researchers hoped that the combination of these two DMARDS may succeed where hydroxychloroquine alone failed, and the initial signs are promising:

21 patients were assigned to receive leflunomide–hydroxychloroquine and eight patients were assigned to receive placebo… From 0 to 24 weeks, the mean difference in ESSDAI score, adjusted for baseline values, in the leflunomide–hydroxychloroquine group compared with the placebo group was −4·35 points (95% CI −7·45 to −1·25, p=0·0078). No serious adverse events occurred in the leflunomide–hydroxychloroquine group and two serious adverse events occurred in the placebo group (hospital admission for pancreatitis and hospital admission for nephrolithiasis)…

Leflunomide–hydroxychloroquine was safe and resulted in a clinical response in patients with primary Sjögren’s syndrome. These results warrant further evaluation of leflunomide–hydroxychloroquine combination therapy in larger clinical trials.

As these three studies were all small trials, more studies will be needed, but as always it is good to see new drugs entering the pipeline, particularly those that can treat the entire disease.

Finally, another eye drop is poised to be available in additional countries soon. Wize Pharma announced positive results in a Phase 4 study of LO2A:

The randomized, double-masked comparative study evaluated LO2A versus Alcon’s Systane Ultra UD (comparator), an over-the-counter lubricant eye drop product used to relieve dry and irritated eyes in DES patients, which is also used to treat dry eye in patients with Sjögren’s syndrome…

LO2A demonstrated clinically meaningful improvement in both the signs and symptoms of DES in patients suffering from Sjögren’s – 100% of the patients treated with LO2A showed a clinically significant improvement in at least one of the primary and secondary end point measurements included in the trial at the 3-month time point vs. 90% of patients treated with comparator. In addition, among the LO2A treatment group, 74% of patients showed a clinically significant improvement in both signs and symptoms vs. 59% in the comparator group.

LO2A is currently available in Germany, Switzerland, the Netherlands, and Hungary, but wider availability would be a boon for the millions of Sjogren’s patients worldwide who suffer from dry eyes.

2020 is almost over, and I hope that everyone is able to enjoy the holidays and face a less disruptive year in 2021.

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Scleral lenses for Sjogren’s Syndrome http://www.whatyousjo.com/2019/11/scleral-lenses-for-sjogrens-syndrome/ http://www.whatyousjo.com/2019/11/scleral-lenses-for-sjogrens-syndrome/#respond Mon, 18 Nov 2019 00:00:10 +0000 http://www.whatyousjo.com/?p=470 ]]> Most contact lens wearers who develop Sjogren’s Syndrome find that they need to bid farewell to their contacts due to eye dryness. Many of these patients don’t realize that there is a contact option that not only allows them to correct their vision, but also provide some dry eye relief.

Scleral lenses are hard contact lenses that are customized to fit individual patient’s eyes. Rather than resting directly on the cornea, like most contacts, scleral lenses have a gap between the cornea and the lens which is filled with a saline solution. Primarily prescribed for patients with for irregularly shaped, thinning, or damaged corneas, many doctors don’t realize the value that scleral lenses can provide to patients with dry eye conditions. Because the contact forms a seal that continually lubricates the cornea with a saline solution, scleral lenses can provide relief from dry eye while correcting vision problems.

There are some potential difficulties to scleral lens use for Sjogren’s Syndrome patients. The first and most troublesome is cost. Because scleral lenses must fit each patient’s eye, they have to be sized by an optometrist familiar with scleral lenses and build based on precise measurements. After the lenses are ordered and shipped, additional measurements are taken while the patient wears them, and new lenses may need to be ordered to provide a better fit. It is not uncommon for scleral lens patients to require several orders to find the best fit. As a result, a pair of scleral lenses can cost over a thousand dollars, and generally must be ordered each year. For those with vision insurance covering ‘medically necessary’ lenses, they may be covered, though not all providers consider sicca diseases to qualify. VSP seems to be the best provider for covering scleral lenses for dry eye patients, but any patient interested in scleral lenses should absolutely consult their insurance company about coverage before ordering.

Other concerns are more procedural. First, scleral lenses are more difficult to insert and remove. The lens must be filled with saline solution and placed in the eye to form a tight seal, which can be challenging for patients used to traditional soft contact lenses. Removing the lens requires the use of a small plunger to break the seal, which also is awkward for new patients. For more information, you can view a demonstration video.

Wearing contacts can also limit the type of over-the-counter eye drops a patient can use, though hopefully they will not need to rely as much on OTC drops while wearing scleral lenses. In addition, the pure, sterile saline needed is generally not sold in pharmacies, though it can be purchased online. Finally, it can be more difficult to travel, as TSA security requires the use of saline containers under 3 ounces, and patients will need to also bring cleaning solution and tools to insert and remove the lenses.

Those conditions aside, scleral lenses are a great option for Sjogren’s Syndrome patients with less than perfect vision. If you are interested, ask your optometrist or ophthalmologist about the possibility of getting scleral lenses.

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Sjogren’s Syndrome clinical trial updates, including Orencia (abatacept) http://www.whatyousjo.com/2019/06/sjogrens-syndrome-clinical-trial-updates-including-orencia-abatacept/ http://www.whatyousjo.com/2019/06/sjogrens-syndrome-clinical-trial-updates-including-orencia-abatacept/#comments Sun, 23 Jun 2019 18:53:41 +0000 http://www.whatyousjo.com/?p=462 ]]> There was a much longer gap than I expected since my last post, so I’d like to start by looking at some updates in the clinical trial space for Sjogren’s Syndrome.

The first trial I would like to look at is the abatacept (Orencia) phase 3 trial, which I have blogged about several times, and the news isn’t good. First, the listing on clinicaltrials.gov was updated to move the estimated completion date back 4 years. Rumors are that the trial had disappointing data, and that Bristol-Myers Squibb is trying to figure out next steps. As this is the only systemic SS treatment that could have possibly been made available in the next several years, this is a setback if the rumors are proven true. Unfortunately, there is more bad news from the clinical trial pipeline:

It’s not all bad news however, as there have been several success stories:

  • Novartis had a very successful phase 2 trial of ianalumab (VAY736), a biologic drug, and is working on a phase 3 trial. This is a brand new biologic drug, and if the abatacept trial does indeed fail, ianalumab could well be the first approved systemic treatment for SS patients, though it is still years away.
  • Another Novartis drug, CFZ533, has also completed a phase 2 trial, and another phase 2 trial is pending.
  • RSLV-132, a patented molecule from Resolve Therapeutics designed to reduce inflamation, successfully reduced fatigue (a challenging symptom to treat) in a phase 2 study of SS patients. A phase 3 study is in the works.
  • A phase 2 trial for Petesicatib (RO5459072), a small molecule Cathepsin S inhibitor, has concluded. While the results have been posted, I have been unable to find a summary or future actions.

There are still several drugs in active trials including:

  • A phase 3 trial for IVIG is currently underway for SS-related neuropathies. This treatment has been available off-label, but a successful trial could mean better insurance coverage for SS patients.
  • A small phase 2 trial for Parsaclisib, a kinase inhibitor.

On the dryness side, there are some dry eye treatments making their way through the clinical pipeline:

If you know of any other interesting clinical trial updates, feel free to reach out to me.

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Thanksgiving update with BCG vaccine study results http://www.whatyousjo.com/2018/11/thanksgiving-update-with-bcg-vaccine/ http://www.whatyousjo.com/2018/11/thanksgiving-update-with-bcg-vaccine/#comments Sat, 24 Nov 2018 19:48:11 +0000 http://www.whatyousjo.com/?p=452 ]]> It’s been 6 months since my last post, largely due to a busy schedule and technical issues. I changed computers, and had a little trouble transferring my site management setup. I’ve also had to stop taking Plaquenil/hydroxychloroquine this summer, and the months following made it clear that it had been helping my health. As a result, I’ve been adjusting my remaining treatments to try filling in the gaps.

There are several stories that I want to catch up on, but I thought I would start with an update from June on the BCG vaccine. Long-time readers may recall a posts from 2015 and 2016 on small trials of the BCG vaccine for diabetes patients. Now, the results of one small trial are available, and they appear promising, though there are some caveats:

Patients with long-standing type 1 diabetes given the bacillus Calmette-Guerin (BCG) vaccine showed modestly better glycemic control through a mechanism that appeared to be epigenetic, according to a long-term follow-up study that has generated controversy here.

Starting after the third year of follow-up in the 46 patients in early-phase trials, hemoglobin A1c levels were lower among patients who got the two doses of the tuberculosis vaccine (6.18% vs 7.07% with placebo and 7.22% among untreated T1D patients, P=0.02).

Among the phase I randomized trial patients followed for 8 years, A1c levels were 6.65% versus 7.22% in the placebo group (P=0.0002), Denise Faustman, MD, PhD, of the Massachusetts General Hospital (MGH) Immunobiology Laboratory in Boston, and colleagues reported at the American Diabetes Association annual meeting, days after publication of the overall findings in npj Vaccines

However, a statement from William Cefalu, MD, ADA chief scientific, medical and mission officer, warned that the “findings must be interpreted with caution and cannot be generalized to the more than 1.5 million Americans living with type 1 diabetes.

“It is also critical to note that all of the study participants continued to use standard insulin therapy throughout the trial; it’s not a situation whereby the treatment changed their standard of care (patients no longer required insulin),” he said in the statement…Cefalu called for an adequately-powered, better-controlled intervention trial to show whether there is any efficacy to the BCG treatment…


Six trials with hundreds of patients are ongoing, Faustman said, although phase III might not be necessary, given the long-standing use of this vaccine as safe. “More data to come.”

The news even made some mainstream outlets like NBC and Newsweek. While noting that six trials were ongoing, I didn’t see any specific information on the SS trial that was alluded to in 2016. Still, these results, while limited in scope, could inspire more investment and an expansion of autoimmune diseases studied as targets for treatment by the BCG vaccine. The full study is available publicly from npj Vaccines.

I’d like to end the post by wishing readers a happy Thanksgiving (even if you aren’t in the United States). I hope that we all have things to be thankful for, no matter what the state of our health.

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Study finds that baking soda reduces inflammation, could treat autoimmune diseases http://www.whatyousjo.com/2018/05/study-finds-that-baking-soda-reduces-inflammation-could-treat-autoimmune-diseases/ http://www.whatyousjo.com/2018/05/study-finds-that-baking-soda-reduces-inflammation-could-treat-autoimmune-diseases/#comments Mon, 07 May 2018 23:19:52 +0000 http://www.whatyousjo.com/?p=445 ]]> I saw this study appear up in some mainstream science news sources over a week ago. The essentials of the study are that a group of healthy volunteers were able to stimulate the production of regulatory immune cells by consuming baking soda in water for two weeks, as described in this article:

A daily dose of baking soda may help reduce the destructive inflammation of autoimmune diseases like rheumatoid arthritis, scientists say. They have some of the first evidence of how the cheap, over-the-counter antacid can encourage our spleen to promote instead an anti-inflammatory environment that could be therapeutic in the face of inflammatory disease, scientists report…

In the spleen, as well as the blood and kidneys, they found after drinking water with baking soda for two weeks, the population of immune cells called macrophages, shifted from primarily those that promote inflammation, called M1, to those that reduce it, called M2. Macrophages, perhaps best known for their ability to consume garbage in the body like debris from injured or dead cells, are early arrivers to a call for an immune response.

The study involved both rats and healthy human test subjects. The rats were afflicted with chronic kidney disease. And while the scientists found improvement in rats with kidney disease, the improvements were also seen in healthy rats and humans, and expanded beyond the kidneys:

The shifting landscape, he says, is likely due to increased conversion of some of the proinflammatory cells to anti-inflammatory ones coupled with actual production of more anti-inflammatory macrophages. The scientists also saw a shift in other immune cell types, like more regulatory T cells, which generally drive down the immune response and help keep the immune system from attacking our own tissues. That anti-inflammatory shift was sustained for at least four hours in humans and three days in rats.

So what does that mean for patients with autoimmune diseases like Sjogren’s Syndrome? Should we be rushing out to buy more baking soda?

As I’ve previously mentioned, when considering a potential treatment option, I consider 3 key criteria: evidence, cost, and risk. In this case, we have one small study involving rats and healthy medical students, but no actual autoimmune patients. I consider that weak, if promising, evidence. Fortunately, the cost of baking soda is extremely low. The risks are fairly low as well; people have taken baking soda regularly as an antacid for many years, usually at a rate of 1/2 teaspoon. It is worth considering that baking soda contains significant amounts of sodium (the sodium in sodium bicarbonate), so anyone who is on a low-sodium diet or at risk of sodium-related complications should speak with their doctor before trying the regimen.

The original study was locked behind a paywall, and the article above does not describe the actual regimen in detail. Luckily I was able to find articles with more instructions:

Paul O’Connor, co-author of the study told Down To Earth, “We utilised 2g of NaHCO3 per day dissolved in 600 ml of bottled water – sipped throughout the day.”

2 grams of baking soda is roughly equal to a 1/2 teaspoon, dissolved in water and sipped throughout the day. That is a little over 600 mg of sodium, so if you wish to try this regimen, make sure you take the additional sodium into account for your diet, and speak with your physician about any concerns. Personally, I plan to try this regimen myself, as the costs and risks are quite low and would justify any benefits that I see.

]]> http://www.whatyousjo.com/2018/05/study-finds-that-baking-soda-reduces-inflammation-could-treat-autoimmune-diseases/feed/ 13 Sjogren’s Syndrome Foundation cuts diagnosis time in half and the positive impact on existing patients http://www.whatyousjo.com/2018/04/sjogrens-syndrome-foundations-announcement-of-cutting-diagnosis-time-in-half-and-the-positive-impact-on-existing-patients/ http://www.whatyousjo.com/2018/04/sjogrens-syndrome-foundations-announcement-of-cutting-diagnosis-time-in-half-and-the-positive-impact-on-existing-patients/#comments Tue, 24 Apr 2018 14:19:22 +0000 http://www.whatyousjo.com/?p=440

]]> SS patients know well the difficulty of obtaining a diagnosis. The symptoms of SS are often ascribed to other maladies, side effects, or natural aging. The diversity of symptoms means that many doctors, dentists, optometrists, and specialists see only part of the picture, and poor communication keeps them from assembling the pieces. Doctors are often misinformed about the disease, and blood work for as many as a third of patients is negative. As a result, diagnosis times in 2012 averaged six years. As a result, the Sjogren’s Syndrome Foundation announced a goal in 2012 to reduce that diagnosis time by half.  Earlier this year, they announced that they had reached a goal:

When the Sjögren’s Syndrome Foundation (SSF) first launched our goal, the average time it took for a patient to be accurately diagnosed with Sjögren’s, from the time they started seeking a diagnosis, was nearly six years. This was something we all agreed was too long, and meant that to achieve our Goal we would need to shorten the diagnosis time to less than three years.

Now, in this final SSF 5-Year Breakthrough Goal update, the Foundation is honored and excited to announce that we have not only reached our Goal but have surpassed it, by reporting that the average diagnosis time is currently 2.8 years!

When we first embarked on our Goal, we understood that changing the diagnosis time was an ambitious initiative and one that we might not succeed at, but we also knew it was an important initiative to help the millions of patients who were suffering from the symptoms and not yet diagnosed with the disease. We believed that our Goal would transform the disease because as physicians start seeing more Sjögren’s patients in their practices, they would need to become more knowledgeable of the disease’s different manifestations and the treatment options available.

This initiative focused heavily on educating relevant medical practitioners for whom SS may have been a page in their (often outdated) textbook and a few questions on a test in medical school. Tens of thousands of brochures were distributed to medical offices across the country, and hundreds of volunteers worked as ambassadors to educate medical practitioners. The SS Foundation has also developed and distributed a number of Clinical Practice Guidelines to educate specialists in the fields of dentistry, ophthalmology, and rheumatology. They are to be commended for the considerable work that has been done by their small staff and volunteers, especially when you consider their relatively small budget relative to many other disease nonprofits.

During the first 8 months of my own quest for a diagnosis, I saw many different specialists, but none were willing to label my disease as Sjogren’s Syndrome, even when I raised the possibility based on my own research. If even one of my medical specialists had understood the complexity of SS, I could have saved considerable time and money and realized a diagnosis much sooner. For many patients now facing the same struggle, a diagnosis means piece of mind in knowing what they face, and access to limited treatments.

Unfortunately, as we patients well know, treatments for Sjogren’s Syndrome are very limited. There are no products approved for the systemic manifestations of SS, and off-label treatments like Plaquenil/hydroxychloroquine, Methotrexate, and Rituxan/rituximab have shown limited efficacy. One might question the value of a faster SS diagnosis, especially to those that have been diagnosed for years.

There is, however, a very clear benefit from this campaign for all SS patients. We all want to see better treatments, and the structure of our worldwide healthcare systems mean that pharmaceutical corporations are the gatekeepers who can unlock future treatments that will let us leave the dryness, pain, and fatigue that plagues us behind. These companies are driven by their shareholders, and shareholders want to see a return on their investment. The misguided perception that SS is a rare disease that can be countered with eye drops and water does not inspire investors to spend hundreds of millions of dollars to develop new treatments that they fear will have a limited reach. However, knowing that SS is a widespread disease that has a significant negative impact on the quality of life for patients means millions of patients who would happily pay (or fight their insurance companies) to have better treatments. That is the kind of patient profile that will move pharmaceutical companies to invest in SS treatments, and it can only happen if the doctors and statisticians who advise them understand the scope of the problem.

As a result, SS patients everywhere should be applauding this latest achievement. Not only does this education campaign mean that patients will face less misery during a protracted quest for a diagnosis, but it means that Sjogren’s Syndrome will inch closer to becoming a household name. As more people, particularly doctors, recognize the breadth and depth of the disease, there will be additional resources invested in finding better treatments. In fact, a look at the clinical trial pipeline today shows considerably more trials for Sjogren’s Syndrome than I saw five years ago. A better-educated medical establishment with better visibility into SS patients means more investment in treatments, and that should get every SS patient excited. Hopefully in the not-too-distant-future, we will see TV commercials for a blockbuster drug to treat SS, and we won’t have to answer as many of our friends, family, and acquaintances asking “What’s Sjogren’s Syndrome?”

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ImmuPharma’s Lupuzor fails to meet the primary endpoint in its phase 3 trial http://www.whatyousjo.com/2018/04/immupharmas-lupuzor-fails-to-meet-the-primary-endpoint-in-its-phase-3-trial/ http://www.whatyousjo.com/2018/04/immupharmas-lupuzor-fails-to-meet-the-primary-endpoint-in-its-phase-3-trial/#comments Tue, 17 Apr 2018 14:47:02 +0000 http://www.whatyousjo.com/?p=432 ]]> I woke to extremely disappointing news this morning. In my Hope for 2016 post, I mentioned peptide based drugs as my #2 hope, with Lupuzor being the key candidate. Over the past several years, I have watched the Lupuzor trials carefully, believing that the drug, if approved for lupus, would offer another off-label treatment option for Sjogren’s Syndrome with an excellent safety profile. The topline results of the final phase 3 Lupuzor trial are out this morning, and it appears that those hopes have been dashed:


This is, frankly, terrible news for lupus patients, SS patients, and really the entire community of autoimmune patients. By failing to meet its primary endpoint, Lupuzor will not be approved by regulatory bodies. Essentially, Lupuzor has fallen back to its position in line after its successful phase 2 trial in 2012.

More details have begun to trickle out into the investment media (which is often the best source for clinical trial news). It appears that Lupuzor saw an impressive beneficial result, but the placebo effect may have kept it from reaching statistical significance necessary for a successful trial. The drug performed very similarly to its phase 2 trial results, but the placebo group outperformed its phase 2 results by a noticeable margin:

The data revealed Lupuzor was more effective than the placebo (52.5% versus 44.6%). But because the response rate for those taking the non-active medication plus the “standard of care” was so high the end-point of the study was not achieved… This initial readout was based on 202 patients, including those who withdrew from the trial.

The effectiveness among the 153 that got to the end of the course of treatment was 68.8% (versus 59.2% for the placebo).

In other words, while a healthy 68.8% of the subjects saw benefits from the treatment, 59.2% of those on the placebo + standard of care also saw benefits. While I am not an expert on clinical trials, there is strong evidence that the placebo effect has been increasing in the United States, thwarting the success of clinical trials in many areas. Interestingly, the Lupuzor trial was conducted in six countries outside of the U.S., perhaps indicating that the placebo effect is also increasing in other countries. Unfortunately, the FDA is extremely slow to adapt to changing circumstances, and this is an issue that is likely to remain for some time. This is likley one reason that Bristol-Myers Squibb is conducting its SS abatacept (Orencia) clinical trials in 75 locations across over a dozen countries. There will likely be additional analysis of the failed Lupuzor trials in the coming days and weeks, but it should serve as a warning about the importance of constructing trials with the placebo effect in mind.

So what is next for Lupuzor? There is no denying that an additional phase 3 trial would be expensive and take many more years. Ignoring the placebo results, however, shows a drug that was successful in over two thirds of the patients taking it with zero serious adverse effects. Throwing away those results, as well as 20 years of research and millions of dollars, seems almost criminal. Though cloaked in PR speak, it appears that ImmuPharma would like to continue forward with Lupuzor, but needs more investment dollars:

ImmuPharma said it believes the top line results “provide evidence for the continued investigation into the development and commercialisation of Lupuzor”. It thinks the drug has the potential to offer patients and physicians a much needed effective and safe treatment for lupus.

Following requests from both investigators and patients, ImmuPharma has begun a further study….The plan is to look at the full dataset before making a decision, but the company said there is demand for a new lupus treatment.

It also said there had been “expressions of interest” in the Lupuzor programme and the phase III study.

“ImmuPharma is in ongoing discussions with a number of larger pharmaceutical companies,” it added.

“The results of this study will now be shared with those potential commercial partners. There can be no certainty as to the outcome or timing of these discussions.”

It appears that the best hope is for ImmuPharma to crunch the numbers to show that Lupuzor does have real potential, and for one of the large pharmaceutical companies to agree to  fund additional Lupuzor trials, perhaps after an ImmuPharma acquisition. Whether any decide to gamble on Lupuzor in the future remains to be seen. Either way, Lupuzor will not be available as a treatment for Sjogren’s Syndrome patients for years, if ever.

Updated on 4/17/2018

Tim McCarthy, ImmuPharma chairman, gave an interview following the results. You can view the video yourself (it’s about 7 minutes), but the summary is that he feels that Lupuzor still has a lot of promise and he is confident in its efficacy and safety. He notes that several pharma partners have expressed ‘very strong interest’. He also states that ImmuPharma is still in a strong cash position after raising $10 million.

We shouldn’t forget Lupuzor and I do want to emphasize the fact that Lupuzor is still there and we will continue to push it forward… as far as I’m concerned, we still have an extremely attractive drug.

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Plaquenil/hydroxychloroquine may have more extraglandular benefits for Sjogren’s Syndrome patients http://www.whatyousjo.com/2018/04/plaquenilhydroxychloroquine-may-have-more-extraglandular-benefits-for-sjogrens-syndrome-patients/ http://www.whatyousjo.com/2018/04/plaquenilhydroxychloroquine-may-have-more-extraglandular-benefits-for-sjogrens-syndrome-patients/#comments Tue, 17 Apr 2018 03:36:22 +0000 http://www.whatyousjo.com/?p=428 ]]> Hydroxychloroquine (generic Plaquenil) is often prescribed off-label by doctors for Sjogren’s Syndrome patients despite the fact that it has never been approved by governing agencies like the FDA. I myself have taken hydroxychloroquine for several years. Studies have generally found that hydroxychloroquine offers little benefit to SS patients, though these studies usually prioritized dryness symptoms; a continuing trend of earlier studies that considered SS as simply ‘dry eyes and mouth’ rather than the complex illness that it is. A literature review published in May of last year noted:

This systematic review showed that there is no significant difference between HCQ and placebo in the treatment of dry mouth and dry eye in pSS. Well-designed, randomized, controlled trials are needed to provide higher-quality evidence to confirm our findings, and future studies should focus on some other index or extraglandular measures, such as cutaneous manifestations, to further explore the therapeutic effect of HCQ in pSS.

However, a more recent study from November was brought to my attention that focused not on dryness symptoms, but on many of the other symptoms that can cause even more hardship for many SS patients. This study evaluated a group of 221 patients, of which 170 used hydroxychloroquine, and focused on extraglandular manifestations (pain, fatigue, etc.) and found significant benefits for the hydroxychloroquine group:

Overall, EGM were less frequent in those on HCQ therapy (36.5% vs 63.5%, p < 0.001). Considering each EGM individually, the following manifestations were more frequent in the non-treated group: arthritis (p < 0.001), fatigue (p < 0.001), purpura (p = 0.01), Raynaud phenomenon (p = 0.003), and hypergammaglobulinemia (p = 0.006)…The lower incidence of EGM was observed in patients on HCQ therapy supports its efficacy in pSS. However, further large scale prospective studies are needed to confirm these findings.

The group that did not use hydroxychloroquine had an ~57% higher incidence of extraglandular manifestations, including inflammatory arthritis (joint pain) and fatigue. While it is only a single study, it lends weight to the anecdotal evidence that while hydroxychloroquine may be less useful in treating dryness, SS patients (including myself) have seen benefits with regards to fatigue and pain. While some doctors dismiss hydroxychloroquine for SS patients due to failures in earlier studies, this study lends weight to the idea that hydroxychloroquine should be considered a front-line treatment for SS patients, particularly those for whom extraglandular symptoms are particularly troublesome.

Hydroxychloroquine has one of the best safety profiles of any medication used to treat autoimmune conditions, though regular eye exams and proper dosage are necessary due to a small risk of serious toxic retinopathy. With proper dosing, a major study found that the risk is low for the first 10 years of usage (<2%), but climbs over time, reaching ~20% at 20 years. Higher dosages (>5mg/kg daily) lead to higher risk levels. For a 60kg person (~132 lbs), 5mg/kg means 300mg daily. This site has a useful calculator to find your safe dose. If you are currently taking hydroxychloroquine above a safe level, consider lowering your dose below 5mg/kg. Personally, I hope that better medications are available before I even reach the 10 year mark which will allow me to discontinue use.

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Study Finds that Gut Bacteria Drive Autoimmune Diseases http://www.whatyousjo.com/2018/03/study-finds-that-gut-bacteria-drive-autoimmune-disease/ http://www.whatyousjo.com/2018/03/study-finds-that-gut-bacteria-drive-autoimmune-disease/#comments Mon, 19 Mar 2018 03:56:33 +0000 http://www.whatyousjo.com/?p=423 ]]> I’ve seen this study appear in several places, including more mainstream news outlets. A Yale study, published in the journal Science, found a strong connection between gut bacteria and the emergence of autoimmune diseases. Gut health has been linked to a number of systemic conditions, including autoimmune diseases, but this study provides additional evidence as well as potential treatment options. In particular, the study noted that a specific bacteria that moved to other areas of the body triggered an autoimmune response in mice with a genetic predisposition. From the article:

Gut bacteria have been linked to a range of diseases, including autoimmune conditions characterized by immune system attack of healthy tissue. To shed light on this link, a Yale research team focused on Enterococcus gallinarum, a bacterium they discovered is able to spontaneously “translocate” outside of the gut to lymph nodes, the liver, and spleen.

In models of genetically susceptible mice, the researchers observed that in tissues outside the gut, E. gallinarum initiated the production of auto-antibodies and inflammation — hallmarks of the autoimmune response. They confirmed the same mechanism of inflammation in cultured liver cells of healthy people, and the presence of this bacterium in livers of patients with autoimmune disease.

Through further experiments, the research team found that they could suppress autoimmunity in mice with an antibiotic or a vaccine aimed at E. gallinarum. With either approach, the researchers were able to suppress growth of the bacterium in the tissues and blunt its effects on the immune system.

When we blocked the pathway leading to inflammation, we could reverse the effect of this bug on autoimmunity,” said senior author Martin Kriegel, M.D.

I have always suspected a link between a long-term tooth infection and my own Sjogren’s Syndrome. From the abstract, it appears that antibiotics “prevented mortality in this model, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and T cells.” Unfortunately, the broad, long-term use of antibiotics as a treatment options can decimate healthy bacteria in the gut, causing additional problems. A targeted vaccine may be a safer option to suppress the bacteria causing inflammation without killing off healthy colonies. Like many recent posts, this is early research primarily involving mice, and thus a potential treatment could be some time away. Still, I am always happy to see research targeting the root cause of SS, rather than just treating symptoms.

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