Thanksgiving update with BCG vaccine

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 setting up the software that I use to post. 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 a lot of 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.

Posted in Clinical Trials, Research, Treatment Tagged with: ,

Study finds that baking soda reduces inflammation, could treat autoimmune diseases

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.

Posted in Research, Treatment Tagged with:

Sjogren’s Syndrome Foundation cuts diagnosis time in half and the positive impact on existing patients

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?”

Posted in Diagnosis, Publicity, Research, Treatment Tagged with:

ImmuPharma’s Lupuzor fails to meet the primary endpoint in its phase 3 trial

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:

  • LUPUZOR DEMONSTRATED SUPERIOR RESPONSE RATE OVER PLACEBO IN PRIMARY ANALYSIS ON FULL ANALYSIS SET OF ALL 202 PATIENTS
  • SUPERIOR RESPONSE DID NOT ALLOW STATISTICAL SIGNIFICANCE TO BE REACHED (P = 0.2631) AND TRIAL’S PRIMARY END POINT WAS NOT MET
  • IN PATIENTS WHO HAD ANTI-DSDNA AUTOANTIBODIES LUPUZOR DEMONSTRATED A SUPERIOR RESPONSE RATE OVER PLACEBO
  • STUDY CONFIRMED SAFETY PROFILE OF LUPUZOR WITH ZERO SERIOUS ADVERSE

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.

Posted in Clinical Trials, Treatment Tagged with: ,

Plaquenil/hydroxychloroquine may have more extraglandular benefits for Sjogren’s Syndrome patients

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.

Posted in Research, Treatment, Uncategorized Tagged with: ,

Study Finds that Gut Bacteria Drive Autoimmune Diseases

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.

Posted in Research, Treatment

Experimental gene therapy functionally cures SS in mice

It’s been a long time since my last post, due to a combination of holiday travel and issues with the software that I use to manage this site. Luckily things appear to be back on track, and I’m ready to address a backlog of potential posts.

This promising study was published in 2016, but I only noticed it recently. This is a very early study with mice, so there are many hurdles and uncertainties to overcome before this therapy could potentially be available. Still, it is quite promising. From the abstract:

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease that is estimated to affect 35 million people worldwide. Currently, no effective treatments exist for Sjögren’s syndrome, and there is a limited understanding of the physiological mechanisms associated with xerostomia and hyposalivation. The present work revealed that aquaporin 5 expression, a water channel critical for salivary gland fluid secretion, is regulated by bone morphogenetic protein 6. Increased expression of this cytokine is strongly associated with the most common symptom of primary Sjögren’s syndrome, the loss of salivary gland function. This finding led us to develop a therapy in the treatment of Sjögren’s syndrome by increasing the water permeability of the gland to restore saliva flow. Our study demonstrates that the targeted increase of gland permeability not only resulted in the restoration of secretory gland function but also resolved the hallmark salivary gland inflammation and systemic inflammation associated with disease. Secretory function also increased in the lacrimal gland, suggesting this local therapy could treat the systemic symptoms associated with primary Sjögren’s syndrome.

What is most promising to me is that the treatment, which was meant to address the sicca symptoms of SS, also resolved systemic inflammation. This demonstrates that the two are certainly linked, and that while systematic treatments like biologic drugs often fail to address all symptoms (especially sicca), future treatments may provide full relief. I will admit that I am not an expert in gene therapy, and much of the study was too advanced for me, but injecting specific proteins into salivary glands seems like a reasonable vector for a human treatment. Of course, this is very early research, and even in the best case a potential treatment is likely a decade away. Still, it is always nice to see potential treatments come out of the gate with full symptom resolution, even if only in animal studies.

 

Posted in Research, Treatment

Another dry eye treatment, Elate by Cambium, cleared for phase 1/2 trials

It has been nearly 15 years since Restasis was approved to treat dry eyes. SS patients had to make due with Restasis until last year when Xiidra was approved. The floodgates seemed to have opened, as a variety of dry eye treatments, including Lamelleye and Lacripep, have entered trials. Now a new drug company, Cambium, has been cleared for trials of their new drug, Elate:

Cambium Medical Technologies (“Cambium”), a clinical stage company, announced today that the U.S. Food & Drug Administration (“FDA”) notified Cambium on September 22 it has completed review of Cambium’s Investigational New Drug Application (IND) submitted late August and that the Study titled A Randomized Multicenter Double-Masked PlaceboControlled Parallel Phase I/II Study to Determine the Safety and Exploratory Efficacy of Topical Fibrinogen-Depleted Human Platelet Lysate in Patients with Dry Eye Secondary to Graft vs. Host Disease–can begin. The Company’s Study will begin at up to five U.S. clinical sites in late 2017 or early 2018, with the support of the Company’s strategic partner AventaCell BioMedical Technology Corporation, Ltd (“AventaCell”).

“We are delighted this Study is about to start,” said Terence Walts, President & CEO of Cambium. “Dry eye is the #1 disease in eye care. There is no cure. We continue to believe the potential for a standardized, commercialized, allogeneic (vs. autologous) and eventually FDA approved growth-factor enriched biologic for dry eye—remains significant. Dry eye is a multifactorial disease of the corneal surface with no single etiology. It is possible therapies with not one a.i. but numerous nutritive/regenerative components targeting not one but several dry eye etiologies—will eventually help clinicians better address the often de-habilitating symptoms of dry eye and among a broader patient population.

This is an early trial targeted at patients with Graft vs. Host Disease, a terrible condition that is similar to many autoimmune diseases. Mr. Walts notes that dry eye is a major problem in many different diseases, and that Cambium hopes that their treatment will have broad applications. Their website is a bit limited, but does have a fairly decent overview of Elate and how it compares with other treatments. Interestingly, they seem to be focusing on Elate as an alternative to autologous serum drops. Elate seems to be similar in mechanism, but uses platelets from blood centers rather than blood drawn from the patients themselves.

As always, the clinical trial pipeline moves slowly, but it’s great to see so many options that could be available in the next decade.

Posted in Clinical Trials, Research, Treatment Tagged with: , ,

Small study finds vagus nerve stimulation reduces fatigue in Sjogren’s Syndrome

Fatigue may well be the most challenging symptom of Sjogren’s Syndrome, or any chronic illness, to treat. It’s pervasive, largely invisible, and has a significant negative impact on the lives of SS patients. So when I see a study, even a very small one, mentioning a non-invasive treatment reducing SS fatigue, I take notice.

In this case, the treatment itself is the gammaCore device, used to externally stimulate the vagus nerve. This nerve is the largest autonomic nerve in the body, responsible for much of our non-voluntary nerve activity, and running from the head to the digestive system. Stimulation of the vagus nerve has been used to treat epilepsy, cluster headaches, and more. Now, the device has been trialed with a small group of 15 female pSS patients in the UK, and the findings are promising:

PRO-F, and Daytime sleepiness were significantly reduced across three visits. Trends of improvement were also observed in Abnormal fatigue VAS, ESSPRI-Dryness and ESSPRI-Physical fatigue subscales. Participants who appeared to have a sustained reduction in fatigue related PROMs over the study period concurrently had a significantly higher proportion of T-cells at most time points. Cytokine production, particularly TNFα by whole blood cells upon LPS stimulation was reduced over the period of device use. Additionally, TNFα and IL-1β levels were significantly reduced after the first device use compared with pre-VNS… These preliminary observations suggest that in some individuals, nVNS may reduce clinical symptoms of fatigue, which could be underpinned by biological changes detectable in the whole blood.

Unfortunately, I have only been able to find the abstract, which is quite limited on details; it is not clear what proportion of the 12 patients found relief, nor how significant the reduction in fatigue actually was. This was only a poster presentation at a conference last month, and I’m hoping the authors post more details of their study soon. Still, the study shows promise. In the United States, the FDA has approved the gammaCore device for the treatment of episodic cluster headaches, meaning that the device could potentially be prescribed for the off-label treatment of SS patients as well. While the evidence for SS treatment is still limited, the device itself appears to be a one-time purchase of around $400-500. While this is not pocket change, it is roughly the same price as a single month’s prescription for Restasis or Xiidra, and less than a single dose of any SS-related biologic drug. It is certainly something that I will be discussing with my doctor during my next appointment.

Edit: based on Lydia’s comment below, it appears that the price for the gammaCore device must be paid monthly to renew its battery. This makes it considerably less affordable.

Posted in Research, Treatment Tagged with: ,

RSLV-132 – Another Sjogren’s Syndrome treatment enters clinical trials

I try to track new entries on clinicaltrials.gov, and a few weeks ago I noticed a new entry in the SS space; a phase 2 trial for a new drug labeled RSLV-132 in the United Kingdom. The company sponsoring the trial, Resolve Therapeutics, appears to be quite small and focused on few treatments for Lupus, with RSLV-132 being their most advanced drug. The compound is currently in phase 2 trials for both SLE and SS, after a successful phase 1 trial. The phase 1 trial, though focused on safety and tolerability rather than efficacy, was nonetheless positive, with no significant adverse effects. While actual information on RSLV-132 is a little challenging to find, there was some information in a press release:

RSLV-132 is a novel Fc fusion protein consisting of human RNase attached to the Fc portion of human IgG. The goal of the therapy is to reduce the burden of circulating RNA-containing immune complexes which are thought to be the most proximal trigger of the systemic inflammation characteristic of SLE. By eliminating the RNA cargo contained in circulating immune complexes the therapy is designed to prevent chronic activation of nucleic acid sensing toll like receptors (e.g TLR7 and TLR8) and subsequent activation of the interferon inflammatory cascade. Additional therapeutic benefit is thought to result from dampening B-cell activation, as well as mitigation of the direct tissue damage caused by immune complex deposition in key organs, such as the kidney and brain.

It does not appear, then, to be another biologic drug, but a specific protein meant to attach to patient’s own proteins and halt the cascade of inflammation caused by our immune systems. While small, the phase 2 trial is estimated to be completed early next year. At that point, we will hopefully see more data about its effectiveness and plans for future trials. As most drugs at this stage do not actually obtain regulatory approval, it’s always good to see more options in the pipeline.

Posted in Clinical Trials, Research, Treatment Tagged with:
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