There are so many turns in the path every day of our lives, so many choices to make, that determining the right choice becomes an important skill. Dealing with a chronic illness may change the kinds of choices we face, but the process of weighing options and consequences remains the same. This past week, in which most U. S. residents celebrated Thanksgiving, I went through this process and came to a decision about how I wanted to celebrate the holiday. Health was one of the factors in my calculus, as was tradition and a sense of legacy. In the end, a compromise was reached, one that carried a risk but also the promise of rich reward.
Nine years ago my granddaughter was born; I've had lupus for more than twenty years. While I'm actively engaged with my granddaughter--we play board games, dance, draw, write stories, dress dolls together--there has always been in our relationship the influence of lupus. My granddaughter knows I cannot go in the sun; I get "tired"; if she has a cold I wear masks and gloves. As involved as I am with the child, lupus has been a factor.
This year it occurred to me that my granddaughter has never seen me cook a holiday meal; these home-cooked feasts have always been a part of my family tradition, but for the last nine years they have been prepared at someone else's house or at a restaurant. It was time, I decided, for culture to be transmitted.
I made my plans with a nod toward practicality. The formal holiday repast would still be consumed at a restaurant, but a separate meal would be put together the night before. At this event there would be no time pressure, no responsibility for making sure everyone had a satisfactory culinary experience. The pre-holiday exercise would provide the leftovers that are almost as important on Thanksgiving as the meal itself.
The choice to assemble this large meal was made in the context of another choice I'd made--to stay off prednisone for as long as possible. Prednisone, I am well aware, is a treacherous friend, one that seduces by offering relief and then betrays by inflicting organ damage. (See an article in Oxford Journals for a discussion). It was likely that if I went forward with the pre-Thanksgiving meal my prednisone hiatus would be over.
The evening before Thanksgiving went well. My son shopped and supervised little fingers as they learned to chop and dice sweet potatoes, olives and nuts. At one point, about two-thirds of the way through, my legs quivered. That was a sign. As the Hospital for Special Surgery states, if you have lupus, fatigue may be an issue and "...when fatigue hits, you need to let go and rest". But my mission was not complete; so I pressed on.
At 5:30 the next morning I began a low-dose regimen of prednisone. Perhaps the necessity for taking prednisone would have come about if I hadn't cooked--there's no way to know for sure. Some seven hours later the family met in a restaurant for dinner; I made it but could not eat.
Increasingly, as time passes, I reflect upon the choices I make and the value I want to harvest from my days. At my age this is a different calculus from what it might be for someone younger. The gift of time has already been granted to me, and it has been appreciated. Which means it's reasonable to ponder, do I want to secure maximum time possible from life, or is it more important to extract from the time left maximum significance?
This Thanksgiving I settled on significance. I'd love to feel great and to be off prednisone, but I made a choice within the reality of my circumstance. This is no different from what everyone does all the time. Choices have consequences. If a chronic illness is in the equation, the consequences may be different but no one gets a free pass.
I'm OK with that.
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 Americans 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.