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‘Pharmacology’ is the third part  of Jessica Grace’s ‘Medicine beyond the textbook’ blog series. The blog posts, released every two months, share Jessica’s stories and thoughts as both a medical student and rare disease patient.

Pharmacology is a fundamental part of medicine; knowing the side effects a drug can cause and weighing these against the potential benefit to the patient.

In 2012, I was diagnosed with a rare auto-inflammatory condition and started on high-dose steroids.

Whilst steroids are hugely effective at reducing inflammation, they are notorious for their numerous side effects; from the puffy face known amongst medical professionals as ‘moon face,’ to the weight gain, cataracts and osteoporosis. [/two-third][one-third] medicine-beyond-the-textbook-blog-jessica-with-text-darker[/one-third][/row]

After four years of steroid treatment, my bones are more osteoporotic than a ninety year old and I’ve already had a spontaneous rib fracture. I have gained five stone in weight and will likely require surgery on my cataracts in the future.

Like many rare diseases, my condition has no set treatment so my consultant was forced to try different therapies in the hope something would work.

When I failed to respond, I was started on Cyclophosphamide; better known for its use as a chemotherapy agent.

For the first time, my blood results and symptoms began to improve, but the price I would pay was a steep one. Not only did I lose all my hair, but the drug has a range of major side effects, from bladder damage to pulmonary fibrosis.

Being heavily immunosuppressed had its own consequences. There was the time I urinated blood for weeks, the time I went into respiratory failure, the time I had a seizure because my fever was so high, the many hospital stays.

To an outsider, it might appear that such medications carry too many risks. But for patients who are severely disabled, in extreme pain, or unable to function (as I was prior to treatment) any health improvement might be worth the side effects.

What can be difficult, however, is when patients must try multiple drugs before finding one that helps. This is often the case for rare diseases where there is no standard go-to therapy.

Here, the issue of risk versus benefit is compounded as medications may have heavy side effect burdens despite no guarantee they will actually help.

In recent years, there has been increased focus on diseases affecting very small patient populations. However, the plight of rare disease patients is still overlooked, with only 5% of these diseases having effective treatments.

One of the key challenges in rare disease drug development surrounds the small numbers of patients available for clinical studies. Additionally, funds for research on rare conditions with such a small market are often more scarce.

In an ideal world, treatments optimising patient well-being with minimal adverse effects would, of course, be preferable. But until such treatments are developed, patients like me are forced to accept the myriad of side effects often accompanying the only drugs that make a difference.

It is important to recognise that patient attitudes towards the risk-benefit trade-off may differ depending on disease severity. Those suffering considerable disability may be more willing to tolerate side effects.

In fact, rare disease patients have been shown to attach greater value to any improvement in their symptoms than those with more mainstream (and easier to treat) conditions, with one patient stating, “any improvement outweighs any side effects.”1

As for me, would I do it all again? Would I be bald, overweight, hospitalized for weeks on end… My answer would always be yes. Because the burden of these side effects was incomparable to the burden of my disease untreated.

As medicine continues to advance and we gain greater understanding of disease pathophysiology, there are reasons to be optimistic for the future of rare disease drug development. In the meantime, as Hippocrates summarises “extreme remedies are very appropriate for extreme diseases.”

Decisions to prescribe medications to patients should never be taken lightly, but for many patients, the possibility of symptom relief makes the risk of adverse effects exactly that; worth the risk.

After all, what price would you place on your quality of life?

1. Morel T., et al., (2016). Quantifying benefit-risk preferences for new medicines in rare disease patients and caregivers, Orphanet Journal of Rare Diseases, 11: 70