One more untold story of this community is how we have helped to secure access to intravenous or subcutaneous immunoglobulin (IVIG or SCIG) therapies for as many SCLS patients as possible.

In the years after its founding, especially during 2009-2014, and ahead of a number of medical articles being published touting the benefits, our RareShare community was essential to spreading the good news about the successful use of immunoglobulin therapies to prevent episodes of SCLS. Not only that, it was through our RareShare community that SCLS patients around the world were helped to obtain access to IVIG or SCIG treatments after finding out about them. This is how the existence of our virtual community proved vital to saving dozens of lives.

There are some old discussion topics one can visit to see this amazing dissemination and support process in action, for instance here (from September 2010), here (from February 2011), here (from September 2011), and here (from January 2012).

During those early years, and with the help of fellow members of our virtual community, I put together an electronic package of continuously updated information on IVIG treatments for SCLS. As new members joined, they would be told about it and would request it to read, pass on to their physicians, and then present to their private or government health insurance companies — to obtain approval for their immunoglobulin-based treatments. The package included testimonials from medical doctors and whatever case studies or other printed materials had come out anywhere in the world supportive of immunoglobulin treatments for SCLS.

Over time, as more and more articles came to be published in the medical literature touting the benefits of IVIG or SCIG therapy for SCLS – and by now I count at least 25 such supportive articles – doctors and insurance companies have been able to find answers without needing to rely as much on their SCLS patients, and in turn on this RareShare community, for essential information. This was of course a benefit derived from our communal efforts to increase awareness of SCLS, thereby encouraging recognition of this illness and the administration of helpful episode-management and preventive treatments, as detailed in Part 3 of this series.

The ongoing challenge, however, is to obtain and keep covered access to intravenous or subcutaneous immunoglobulin therapies for as many SCLS patients as possible. It is a challenge everywhere because immunoglobulins are very costly. They are not produced in laboratories from artificial ingredients but, rather, harvested from hundreds of blood donors to produce what is needed for our treatment cycles.

To illustrate, one liter of plasma provided by at least two donors yields a mere 4.5 grams of IVIG, so it takes 40 liters of plasma, or at least 80 donors, to source the 180 grams of IVIG that a 90-kilogram adult like me receives every month – which adds up to 480 liters of plasma provided by at least 1,000 donors to supply me for one year of treatments.

The cost to process this plasma is also high because the collection, handling and storage of plasma, and the manufacturing processes involved, are highly regulated at every step to safeguard the purity of plasma-derived products against transfusion-transmittable microorganisms that can cause diseases like AIDS and hepatitis.

And then there is the fact that worldwide demand for plasma-derived therapies has been growing very rapidly thanks to experimental use. For example, while the U.S. Food and Drug Administration (FDA) has approved a half-dozen indications for immunoglobulin use, it is estimated that the medical community has identified more than 200 indications, mostly rare diseases, that benefit from immunoglobulins – such as in the case of SCLS – thereby greatly boosting the demand for so-called, off-label use of IVIG and SCIG.

Limited and costly supplies and growing demand have combined to hike the market price of immunoglobulins to stratospheric levels. In the United States, for example, IVIG is priced by hospitals providing it at between $30-70,000 per monthly adult dose, depending on body weight and manufacturer, which translates to $350-850,000 per year.

These are not the price tags that insurance companies validate (namely, they usually pay two-thirds to three-quarters of the posted price, and providers forgive the remainder as per long-term contracts), but they are the sticker prices that an uninsured or otherwise uncovered SCLS patient would have to confront if they were on their own.

Therefore, hospital infusion centers will generally not administer immunoglobulins to patients on a preventive regimen – medical emergencies in-hospital are another matter, because insurance companies do not question and thus cover them – unless patients show proof, in the form of a valid prior authorization, that their private or other health insurance carriers will cover the procedure.

In countries with government-run health insurance plans, rationing of immunoglobulins does not take place via the price mechanism but instead through making them available to some patients but not to others, or else by making them available in smaller-than-recommended doses. For example, we have in our community some European patients who have been put on 1 gr/kg monthly doses (rather than on 2 gr/kg), and that is usually not by patient choice but by decision of their physicians under cost-control pressure from their hospitals and insurance systems.

In a recent article by Dr. Zahir Amoura (see Part 2) and nearly 30 other physicians on their management of SCLS patients throughout Europe, their prevailing approach to IVIG is explained as follows: “The monthly treatment with 2 gr/kg was administered during a minimum of 1 year. In the absence of a 1-year recurrence and after the approval of the coordinating center, the IVIG treatment could be tapered to 1 gr/kg monthly and then, after another year free of recurrence, to 0.5 gr/kg monthly. After achieving the dosage of 0.5 gr/kg monthly, we considered on a case-to-case basis whether to increase the interval between the IVIG infusions. In case of relapse, the IVIG treatment was returned to the previous step.” Unfortunately, Amoura and colleagues are silent on what percentage of their patients have been stabilized at each lower level of dosage, and on what percentage of them have experienced a relapse.

In the United States, we have one large government-run health insurance program to which life-long contributions are mandatory, and it is the one covering those who retire or who are deemed disabled – Medicare. And Medicare engages in its own forms of rationing: for example, it does not cover dental, hearing, vision or foot care, nor the expense of caring for persons who cannot take care of themselves. It also rations care by paying physicians and hospitals much less for services rendered to their Medicare patients than private insurers compensate for their subscribers' care. Therefore, doctors have an incentive to make Medicare appointments shorter than others (say, 10 minutes rather than the usual 20 or 30 minutes), and hospitals have an incentive to discharge Medicare patients sooner than others – before they are fully cured.

A decade ago, very few SCLS patients in the United States survived until old age, and none were receiving immunoglobulins, so ensuring continuity of care in retirement was not an issue. However, in recent years, several of us have made it past age 65, and have done so thanks to IVIG treatments, so we have now gained experience in how Medicare deals with us. In short, Medicare rarely approves coverage of IVIG for SCLS or other conditions that are not the six that are FDA-approved. Some of our patients on Medicare are getting IVIG, but that is because their compassionate physicians claimed that they suffer from one of the six illnesses for which immunoglobulins are FDA-approved.

The first member of our community to do something to ensure wider access to immunoglobulins for himself and other SCLS patients was Warren King (WazzaACT), who in 2012 mobilized his hospital and doctors in Canberra to get the Australian National Blood Authority to approve the supply of IVIG for SCLS patients throughout that country on an exceptional basis, see here and here. Every SCLS adult and pediatric patient in Australia has since benefited from this access, and thus our community has a debt of gratitude to Warren for his initiative and success.

There are two initiatives that I have been working on for the benefit of patients primarily in the United States. The first is to recruit a major manufacturer of IVIG and SCIG to initiate the process of obtaining FDA approval for SCLS as an indication for immunoglobulin treatments, and I am extremely pleased to announce that I have recruited such a sponsor. To make a long story short, it took me more than two years, and the application process will likely take another two-to-three years to yield fruit, but at least the process is now in motion. And if the FDA were to approve IVIG and SCIG for SCLS, chances are that many regulatory agencies in other countries around the world would follow the FDA’s lead.

What increased the odds of this initiative is a new law, “The 21st Century Cures Act,” passed by the U.S. Congress and signed by then-President Obama at the end of 2016, which among other things expedites the process by which new drugs and devices are approved – mainly by easing the requirements for FDA approval on new products or new indications for existing drugs. For instance, under certain conditions which we believe SCLS meets, the Act allows drug and device companies to provide data summaries and clinical evidence, such as observational studies, patient input, and anecdotal data, rather than full – and very lengthy and expensive – clinical trial results. This change is crucial because, given the small number of SCLS patients, and the amazing success of immunoglobulin treatments, double-blind, randomized clinical trials – the FDA’s prior requirement – are not only impractical but would be unethical. (Can you imagine giving half the SCLS patients in the trial IVIG and the other half mere saline, when the latter group would be at high risk of having, and possibly dying from, an episode?)

The second initiative has been to challenge the Medicare denials of immunoglobulins for SCLS, because Medicare’s laws and regulations establish that the program may cover a particular use of a drug that is not indicated on its approved labeling (namely, “off-label” use) if such use is medically accepted, necessary and reasonable. For this purpose, two years ago I recruited the healthcare attorneys of a leading U.S. law firm, who kindly agreed to volunteer their time and effort to help me, and lately also another member of this community, to go through the requisite, multilevel appeal process mandated by Medicare. To make another long story short, I have been winning my Medicare appeals, and recently we obtained a ruling from a U.S. federal court judge stating specifically that prior denials of Medicare coverage of my IVIG treatments are “unlawful, set aside, and reversed.” See here. Now we are working to make this ruling set a useful precedent applicable to all other SCLS Medicare beneficiaries, starting with the other member of this community who has been denied coverage for his treatments.

Dear Arturo, how much work you do not imagine and how good you take the time to tell it. Thanks for your efforts, I will not reach what I lack of life to thank. My life would not be the same without his work. I feel indebted to you.

Wow,Arturo. Great work.As you rightly say,the FDA approving this would be of global benefit. Thank you so much for your ongoing hard work. Brilliant. 

Thank you so much for you work.