A New Adventure

northern lights 225524_1280

Northern Lights

A little less than a year ago I embarked on a new endeavor.  This undertaking was less about ambition than it was about awareness of fleeting opportunity.

Readers of this site know I’ve had lupus for about twenty-five years.  Like most people who negotiate a bout of serious illness, I gained valuable insight from the experience: time is a gift of the present, not the future. At any moment the future may be snatched away. So I use the present, every moment of it, as fully as ability and physical setting allow.

My latest adventure is a joint project with my daughter.  This collaboration is enormously satisfying, as is the work itself.  I volunteered to write books for my daughter’s fledgling business.  Her company, Rhythm Prism Publishing, produces books that enrich and educate people of various ages. The ideas for the books are mine; there are no other writers on staff.

So far, we’ve put out ten books; six of these are educational books for children.  Topics are chosen very carefully. These are not narrow in focus but lend context to world events.  There are biographies of Marie Curie, Florence Nightingale, Jonas Salk and Rabindranath Tagore.  There is a book on radioactivity and one remarkably brief discussion of the modern British Empire. Two writing manuals and a companion teacher’s guide are also available.

I love to write, so it is not surprising that I share this love.  Not only are there writing manuals for children, but there are two guides to writing designed for adults who would like to put together a record of their lives.

My only compensation for all this writing is the benefit it may give my daughter and the great pleasure I get from the activity itself.  I don’t know when I will write my last blog, or my last book.  Whenever that is, I won’t be taken by surprise.  My future will not be snatched from me because I’m living it right now.

Epratuzumab: Targeting B-Cells To Treat SLE

As research laboratories across the world investigate new lupus treatments, efforts increasingly focus on suppressing B-cell activity.  B-cells are major actors in the normal immune response.  With lupus, the immune response is not normal and neither is the behavior of B-Cells.  During an active disease phase, the immune system attacks organs and wreaks havoc. B-cells play an important role in this process.
Historically, lupus medicines have sought to control the aberrant immune response by tamping down the entire immune system.  Established remedies (for example: glucocorticoids  and cyclophosphamide) are not very specific in suppressing the immune system. Instead of acting on the parts of the system that are especially aggressive, older medicines depress the general immune response. While this approach is often effective in controlling symptoms, it can sometimes have a devastating impact on the overall health of the patient.
An analogy to the traditional approach might be found in the case of a broken light switch. In order to repair the switch, an electrician could shut down all the circuits in a house. This certainly would insure that electricity isn’t flowing to the broken switch–it would also insure that electricity isn’t flowing anywhere else in the house, either. A total shutdown might have far-reaching consequences–melting ice cream, for instance.  However, if the electrician decided to shut off only the circuit associated with the broken switch–that is, if she/he targeted the problem area–disruption in the household would be minimized.
That’s the principle behind targeted B-cell suppression. If only B-cells are affected, the impact on the patient might not be as widespread as it would be if an older generation, immune-suppressant drugs were administered.
The problem with new generation, B-cell-targeting drugs is that, so far, they haven’t proven to be very effective. This is the case with belumimab and rituximab. While both of these drugs are prescribed at present and do help people in certain situations, neither has lived up to its early promise.
Epratuzumab is a B-cell-targeting drug with a difference. This drug doesn’t try to suppress all B-cell activity.  It is designed to address only a specific part of the B-cell: CD-22, which is on the surface of the cell.
It is believed that a major benefit of epratuzumab over other B-cell-targeting drugs may be that it does not depopulate all of the B-cells in the course of treatment. It seems that epratuzumab only eliminates “up to 45% of circulating B-cells“.  Rituximab, on the other hand, eliminates  greater than 90% of circulating B-cells.  Since B-cells are essential for a robust immune response, wiping these cells out increases the risk of infection. Keeping viable B-cells might help to limit that risk.
Epratuzumab has gone through Phases I and Phase II clinical trials. Phase III is currently underway.  A January 2013 article published in the Annals of Rheumatology describes the drug as promising. The journal reports that epratuzumab was well tolerated by study participants, even at high doses (2400 mg. week); also, the journal reports, trial subjects who received the medication experienced better outcomes than the control group that received placebo.
In February 2015 Euroscan (a European evaluating organization) issued a report on the safety of epratuzumab and side effects experienced by study subjects. Side effects were noted to have occurred as follows: 10% experienced conjunctivitis; 45% upper respiratory infections; 28% diarrhea and 28%  headache; 14% experienced migraine and 34% caught a cold; 24% experienced nausea; 24% had bronchitis; dizziness was reported by 10%; 10% ran a fever; sinusitis was reported in 31%; abdominal pain occurred in  31%; 10% had chest pain; 10 % had a cough.
Phase III of the epratuzumab clinical trial has 1400 participants; these patients have moderate to severe SLE. The final report on Phase III will be issued in 2019.  The drug’s manufacturer, UCB and Immunomedics is optimistic, based on the results of  Phase I and Phase II.  UCB reports that study participants who received epratuzumab showed a  “24.9% treatment advantage over placebo”.
Will epratuzumab  be a ‘magic bullet’ for lupus patients? A lot of people certainly hope so. Clinical trials and actual practice will prove whether or not this hope is misplaced.

Rituximab Update

In September of 2012 I posted a blog about a biologic, Rituximab.  Some researchers had hoped this medication would prove to be an effective treatment for SLE.  Unfortunately, Rituximab  did not live up to expectations. However, the drug has been used to treat SLE  in rescue situations.  As such, it is tried when other options have failed. In many of these cases, Rituximab has been effective, especially when used along with  other drugs.
Even though clinical trials of Rituximab have not yielded promising results, investigation continues to see if it might be useful as part of a regimen with other lupus treatments.  As  experience with Rituximab accumulates–in doctors’ practices and in trials–data  is collected about potential side effects.  It is important for physicians and patients to be alert to these so that prompt action may be taken, if necessary.
A 2015 Hindawi Journal article reports a case of early-onset neutropenia and thrombocytopenia that was associated with the administration of Rituximab. The patient’s treating physicians entertained the possibility that these conditions may not have been caused by Rituximab but may have been a manifestation of SLE.  This analysis was rejected because the patient’s clinical profile did not support the conclusion.
This case of early-onset neutropenia and thrombocytopenia associated with Rituximab is unusual, if not unique. The authors of the Hindawi article contemplate the possibility that the side effects  may have also occurred in other cases but were not detected.
In any event, both  neutropenia and thrombocytopenia were transient in this case.  The  conditions cleared up 12 days after Rituximab therapy stopped.
risk of neutropenia is infection; a risk of thrombocytopenia is bleeding.
One thing that should be remembered as side effects of Rituximab are discussed: the medicine is used for very sick people, people who may not have many other options. Side effects will likely not be a reason to avoid treatment, but being aware of those side effects may help to keep the patient safe while treatment proceeds.

Accelerating Medicines Partnership

The US government, Big Pharma and non-profit organizations have agreed to work together in a novel approach to finding effective treatments for lupus and other diseases. Called AMP (Accelerating Medicines Partnership), the collaboration would involve pooling research and information in the early stages.  All “partners” in the project would be able to learn from the work of others in the group.  The emphasis would be on finding biomarkers that would aid in the development of targeting drugs.

AMP grew out of the frustration of patients and doctors.  Access to effective drugs for devastating diseases, such as lupus and Alzheimer’s, is woefully limited.  Progress in finding new treatments has been slow. One of the reasons for this, some have suggested, is that competing firms doing research often duplicate the efforts of each and thus waste valuable time.  If all the research results could be pooled and both private and public resources dedicated to exploiting those results, progress might be realized.

The unique aspect of AMP is that although competing private companies would pool information on the early end of research efforts, at some point competing companies would separate and develop their own products. These, then, could be sold for profit. Pooling information would no longer be part of the process.

While AMP seems to offer great potential for advances in the treatment of certain diseases (the list is limited to lupus, Alzheimer’s, rheumatoid arthritis and diabetes), there are some researchers who question the approach.  Dr. Michael D. Lockshin, at the Hospital for Special Surgery in New York, wonders if the AMP approach for lupus is too narrow in focus.  Dr. Lockshin explains that lupus is a disease of many manifestations. He believes that effective treatments for lupus may emerge from AMP but that to eradicate the disease completely,  “...you will need to go into other fields.”

AMP is projected to continue for five years.  Results are scheduled to be reviewed regularly. Whatever questions may be raised about narrow focus or eventual profits reaped, one thing is certain: millions of people will benefit if this collaboration yields effective treatment for even one of the targeted diseases.

Lupus, Fatigue, Muscle Weakness

Lupus, Fatigue, Muscle Weakness

By A. G. Moore

A 2012 study conducted in Australia looked at the relationship between muscle strength and fatigue in women with SLE. Since  fatigue is a symptom reported by more than 50 % of patients with SLE, researchers tried to determine if the fatigue was due to reduced muscle strength.

This study was small–45 women, 24 with SLE and 21 who were  “healthy”. There were two measures of muscle strength examined: functional and isometric maximal. Functional is basically the amount of use a person gets out of a muscle system–it was this measure that correlated with fatigue among SLE patients.

The researchers who ran this study tried to discover factors that might contribute to muscle weakness in lupus patients. Lack of physical activity was considered to be one cause, but this did not entirely explain the differences in muscle strength between the SLE  participants and the “healthy” participants. Levels of Vitamin D were also examined (Vitamin D deficiency has been linked in other studies to muscle weakness). However, there was no significant correlation discerned in this small  study between Vitamin D levels and muscle strength.

The authors of this study conclude: fatigue is widely reported by women who have SLE. Muscle weakness among these women correlated to fatigue, even in the absence of disease activity. And, vitamin D levels were not found to be a significant factor in muscle weakness in the small group of SLE patients studied.

 

Lupus and Travel

Lupus and Travel 
 By A. G. Moore 3/29/2013
 
 
 
The Guardian Angel Cathedral, Las Vegas, NV
 My Husband and I Were Married Here
 Photo by Carol M. Highsmith
 Public Domain

It was about twenty years ago when I first traveled with lupus. I was in medical limbo at the time: the symptoms of lupus were evident but the disease had not yet been diagnosed. My husband and I were vacationing in Las Vegas, his favorite destination. We had been married in that gambling oasis and returned to the city every year, if circumstances permitted.

Las Vegas is Disney World for adults; real-world problems, like money and bad news, are remote and don’t seem to matter. As we walked around the city we knew so well, changes were evident. Old standbys, like the Dunes hotel, which had been our honeymoon retreat, were gone. In the place of these old Vegas institutions were more magnificent, resort-oriented complexes.

There were other, less obvious, but nonetheless pervasive changes that intruded into our trip.

We were walking along Las Vegas Boulevard–the Strip–one afternoon. As was our habit, we eschewed the use of taxis and buses. I struggled during our stroll to match my husband’s energy and my own pre-lupus standards. It has always been my inclination to keep personal battles private, but there was no hiding the fact on this outing that I was lagging.

Finally, my husband turned to me, and said, with his inimitable economy of expression, “It’s like you’re half a person.”

We’d already been in Las Vegas for a couple of days when this insight hit him. It had taken that long for him to realize that, much like his beloved Las Vegas, I had changed. Our vacation was the first time since I had become ill that we had been thrown together so much. Back home, in our every-day lives, we both had jobs outside the home–his entailed a lot of overtime. While he knew before the trip that I was experiencing health issues, the intrusive nature of those issues had not been obvious. But now they were unavoidable.

As we explored our Vegas haunts and sought to build upon memories from the past, my husband understood that the past was gone. He was confronted with a new reality: a new version of Vegas and a modified version of his wife.

It’s spring now and we are planning a trip to Vegas. Our annual pilgrimage was canceled once or twice in prior years because of health issues, but this year we’re ready. The World Series of Poker puts on its main event in late spring and early summer; my husband likes to be in Vegas for this tournament.

Lupus is background noise; it’s something I deal with as I go about my life. The trick is to keep this nuisance in the background and not let it derail my plans. There are certain actions I take to try to insure this will be the case.

The preparations I make for my trip may not be appropriate for other people with lupus, but I think many of these pre-trip measures may serve the needs of some who are living with lupus.

Some of the things I do to get ready for traveling are:

  • Buy comfortable shoes and plan to wear them, no matter how they might look with my clothes. Break in the shoes before the trip. Even if old shoes look O.K., often the cushioning in the sole is not as good as it once was. I plan to do a lot of walking and I need to have joint support.
  • Get extra medication and pack it in at least two places: my carry-on and my suitcase.
  • Start my medication (low-dose prednisone) before I leave, so a stress-induced flare is less likely.
  • Chill out, as much as possible, to relieve the inevitable stress of preparing for a trip. In my case, this means going to my reliable psychologist/hypnotherapist over the next couple of months for sessions. The therapist will give me post-hypnotic suggestions and help me to practice relaxation techniques, such as meditation and breathing exercises. I use the services of this very skilled and sensitive professional the way some people use medication: he’s an effective intervention and, unlike drugs, doesn’t have associated side effects. I’ve posted some links below to websites which describe the very real, therapeutic benefits of hypnosis–whether the goal is to reduce stress or alleviate pain.
  • Locate a doctor in the Las Vegas area who will be available should I get sick while I am on vacation. This is the first year I am doing this. I’ve been sick in Vegas and this is a kind of scary thing to go through on my own. Having a recommended physician on hand will give me greater confidence.
  • Pay extra $  to sit in airplane seats that have more leg room. Seems like an indulgence, but this really helps with joint and muscle problems. Airlines may assign free bulkhead seats to passengers with medical issues. However, the last time I flew and took the bulkhead seat I was not comfortable. Though I could stretch my legs I could not move the seat back. When neck, joint, and back pain are present, seat flexibility is important. I usually bring a small pillow to support my neck. It’s a five hour flight from New York (where I live) to Las Vegas. Added on to that time is surface transportation before and after the flight. With all of this, getting to a destination can be so arduous that by the time I arrive I am already in bad shape. So investing in comfortable seats ends up being more a necessity than a luxury.
  • Stay hydrated. Blood clots are a risk for anyone on a long flight. Most people with lupus and those who are on steroids face an increased risk. Dehydration increases the chance of developing a clot and so does immobility. I try to get up frequently and stretch my legs. The longer the flight, the more important these measures become.
  • Bring some good quality surgical masks (OSHA rating N95) in case someone around me on the plane is sneezing and coughing.
  • Bring non-latex examination gloves and my own soap to protect super-allergic skin. The gloves are not likely to be used but the soap–and my own shampoo/conditioner–are essential travel accessories.
  • Carry a letter from my doctor which indicates to airline screeners that I have a restricted diet and must carry special food on the plane. Then pack that food in my carry-on case.
  • Bring a variety of hats for cover up just in case a restaurant/airline terminal has bright fluorescent overhead lighting. A good, broad-rimmed hat also comes in handy for protection from the Las Vegas sun–although this is a lupus antagonist I have learned to avoid.
  • Make sure the hotel has a small refrigerator reserved. I usually buy a few supplies on my first day in town so that I don’t get into trouble by eating foods that I shouldn’t. Hotels will usually provide a refrigerator free of charge if there is a medical need.

My pre-trip activities obviously are geared toward my specific needs. There are travelers who may have more of an issue with blood clots or immune suppression than I do. There are people who really do have to stay out of crowds and who have more problems with mobility. Careful planning and a conversation with the doctor are always in order.

In preparing to write this brief essay on travel, I looked up a few websites which address the challenge of traveling with lupus. Some of these sites have practical, useful advice. I’ve listed three that I found interesting.

Several sites describe travel adventures which amaze me. One, Wherever with you, is authored by “Kate”, who has lupus. Her article, Traveling with Lupus, describes a journey into the Australian heartland. Kate understands that some people might think she’s crazy to embark on her adventurous vacations, but she explains that she makes accommodations to keep lupus flares at bay. Although I can’t imagine ever emulating her activities, I do admire her spunk and courage. http://whereverwithyou.com/2013/01/23/traveling-with-lupus/

Below are links to two of many websites which cite studies on hypno-therapy. The studies described below show demonstrated benefits when hypnotherapy was compared to control groups that had no therapy and to groups that had an alternate non-pharmaceutical intervention, like meditation. Of course, your doctor should always be consulted when you are considering introducing any treatment modality. Also, the doctor is probably the best place to get a referral. Word-of-mouth and advertisements are not reliable sources.

Two sites which discuss hypnotherapy are:

Lupus and Clinical Trials


 By A. G. Moore 11/23/2013
 Melingue_Jenner
 
 Edward Jenner injecting James Phipps, his gardener's
 son, with cowpox
 Lithograph by Gaston Melengue
 Wikimedia Commons, public domain, Copyright expired

Sixty years ago, when Flannery O’Connor learned she had lupus, one medication was available to treat her disease: hydrocortisone. Twenty years before her diagnosis, Edward O’Connor, her father, learned that he had lupus.  For him there was no treatment. Times have changed since Flannery and her father battled lupus. Today the list of treatment options is long. These options exist because researchers have worked tirelessly to solve the lupus puzzle and because they were aided in their efforts by the participation of countless lupus patients in clinical trials. While much of the work researchers do takes place in the laboratory, the proving ground for their investment is the clinical trial. Currently there are clinical trials underway that are exploring new theories in lupus therapy. One of these theories has been described by Dr. Timothy Niewold, who is a scientist affiliated with the Mayo Clinic. Dr. Niewold is investigating the role of interferon in lupus. There is clear evidence that in some people levels of interferon rise with disease activity. In certain instances, lupus has actually been precipitated by administration of interferon (for an unrelated illness). With the apparent association between interferon levels and lupus, it has been suggested that decreasing interferon production might temper symptoms of the disease. Drugs are being designed that are supposed to do just that. Targeting interferon is one example of the trend in lupus treatment to zero in on specific components of the immune response–rather than suppressing the entire immune system. When Flannery O’Connor was prescribed hydrocortisone, the drug was effective because it stopped her immune system from attacking her organs. However, shutting down the whole immune system is a rather blunt way of dealing with autoimmunity. It’s kind of like trying to weed the front lawn with a scythe; maybe the job gets done, but a whole lot of grass and flowers are sacrificed in the process. Shutting down the immune system can have devastating consequences. It is hoped that by targeting specific actors in the system, treatment may not only be more effective but may have less dramatic side effects. One of the interferon-targeting drugs currently under investigation is sifalimumab. Dr. Niewold (of the Mayo Clinic) explains that an important aspect of research on interferon-targeting medications is understanding how this cytokine acts in people from different ethnic backgrounds. As sifalimumab goes through its different trials, it is becoming clear that interferon does not have equal significance for all ethnic groups. For example, interferon activation in African American SLE patients is dependent on the presence of autoantibodies; this is not true for European Americans. Dr. Niewold states: “This heterogeneity may be clinically important, as therapeutics targeting this pathway are being developed.” Targeting specific aspects of the immune system is the theory behind the development of other lupus therapies. B and T cells, for example, are known to be very aggressive in active lupus. Belimumab , currently prescribed for certain types of lupus, targets B cells and Abatacept, which is an RA drug under consideration for lupus, targets T cells. Both drugs are currently in clinical trials. Clinical trials are essential if new therapies are to come on the market. They also may be of help to those who volunteer as subjects, because there is possibly the opportunity to receive novel and effective treatment. However, every person who volunteers as a subject should be clear about the goals of the study for which they have been recruited. Not every study has as a primary endpoint improvement in participants’ disease status. Some studies examine other aspects of drug development. Volunteers should never lose sight of the fact that participation may carry with it significant risks. One research paper I came across illustrates the importance of being informed before becoming a volunteer. This paper gives the results of a clinical trial in which sifalimumab was studied. The primary purpose of the trial is described: “..to evaluate the safety and tolerability of multiple doses of intravenous (IV) sifalimumab in patients with moderate-to-severe SLE.” Secondary objectives of the trial are also described: “..to evaluate the PK (Pharmacokinetics) and immunogenicity” of the drug. Only as a third and almost incidental objective is observation of the effect sifalimumab has on disease activity. The research paper describes this third objective in the following words: “…measurements of disease activity…were included only as an exploratory end point… ” The clinical trial described by this research paper has obvious significance for lupus treatment; finding out dose tolerance and learning about adverse side effects are important pieces in the development of a possibly valuable lupus intervention. However, these are findings that have general importance and likely will not immediately benefit study participants. It does not seem that those who conducted the study expected subjects in the clinical trial to experience sustained improvement in disease status; that was not the study’s defined prime objective. This leads me to repeat the following: if you are considering being a volunteer in a clinical trial, make sure you understand what it is that the researchers hope to learn from that trial. Does the trial offer participants an opportunity to reap the benefits of new lupus treatment, or are participants merely being mined, as it were, for information that may contribute some day to a good lupus intervention? Know that there are risks associated with participation. In the study described above, for example, some participants did die. Whether or not these deaths were attributable to sifalimumab is not certain, though, as the paper states, for at least two of the deaths, “… a potential role of the drug in contributing to the infection cannot be excluded.” Without clinical trials there cannot be new drugs to treat lupus. Volunteers for these trials are essential if the trials are to succeed. However, if you choose to become a subject, be clear about what it is you are submitting to. And then, if you are satisfied with the risk/reward ratio, go for it. You and everyone else with lupus may benefit.

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