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Pharmaceutical advances since the formation of the NHS in 1948 have transformed the therapeutic landscape beyond recognition, saved countless lives and improved the prospects for many more. It is a heritage we should be proud of, says Mark Greener

As a nation, we are living longer than ever. Between 1915 and 2015, male and female life expectancy rose by about 31 and 29 years respectively, according to the Office for National Statistics. Falling infant and child mortality accounted for most of the increase during the first half of the last century, with most of the increases among older people occurring in the past 50 years.

With the NHS turning 70 years old this month, let us take the opportunity to look at five pharmacological areas that exemplify the therapeutic advances that have contributed to this improved longevity and helped enhance quality of life.

Medicines are not, of course, solely responsible. The contribution made by public health, lifestyle changes and advances in nonpharmacological treatments often exceeds that of drugs – but these five areas illustrate the dramatic, life-transforming changes in the pharmaceutical landscape over the past 70 years of the NHS.

Antivirals

Doctors recognised AIDS in 1981 as young gay men began dying of rare opportunistic infections and developed dark purple Kaposi’s sarcomas on their arms and faces. In 1983, researchers documented heterosexual spread and isolated the retrovirus, which was confirmed as causing AIDS the following year. Zidovudine reached the market in 1987, just six years after the clinical identification of AIDS’.1

There are now six main classes of antiretrovirals, each with a different mechanism of action, so most HIV-positive people receive combination therapy. In particular, the introduction of Highly Active Antiretroviral Therapy (HAART) in 1996 transformed the prognosis for HIV-positive people. Epidemiologists now expect the life expectancy of those who are diagnosed and start treatment rapidly after HIV infection to approach that of the general population.2

Antivirals also raise the realistic prospect of eradicating hepatitis C virus (HCV) infections. According to the Public Health England (PHE) report, ‘Hepatitis C in the UK 2017’, the recent fall in HCV deaths probably reflects increased treatment with new direct acting antiviral drugs – up by nearly 50 per cent over the past year and by almost 90 per cent compared to earlier years.

The 2016 ‘WHO global health sector strategy for viral hepatitis’, aims by 2020 and 2030 to reduce new chronic HCV infections by 30 and 80 per cent and mortality by 10 and 65 per cent respectively. PHE suggests that achieving the 2020 target “seems likely in the UK”. More tellingly, the 2030 target is “within our reach, provided current improvements in numbers accessing treatment can be sustained”.

Vaccines

While antivirals made impressive inroads into the deaths from HIV and HCV, it is hard to think of any pharmaceutical innovation that has had a greater impact on public health since the foundation of the NHS than vaccines. Smallpox immunisation began 150 years before the formation of the health service3 but during the 1960s, for instance, researchers developed vaccines against polio (oral formulation), measles, mumps and rubella.

More recent vaccines prevent cancer (hepatitis B and human papillomavirus) and many deadly infections, including cholera, anthrax, typhoid and some types of meningitis.3

In the US, for example, 530,217 people developed measles in a typical 20th century year before the introduction of the vaccine. This dropped to 69 in 2016. The same year there were no reported cases of smallpox, diphtheria or paralytic polio.

Together, these diseases accounted for 66,374 cases in a typical year before the introduction of the vaccines. Vaccines even protect people who are not immunised, by interrupting human-to-human transmission (so-called herd immunity).4

Nevertheless, a new report from Johns Hopkins University, ‘The characteristics of pandemic pathogens’, warns that respiratory-borne RNA viruses – such as influenza – pose the greatest “global catastrophic biological risk” (GCBR). In other words, GCBR pathogens “could lead to sudden, extraordinary, widespread disaster beyond the collective capability of national and international governments and the private sector to control”.

The report makes several suggestions to tackle GCBRs. Surveillance and treatment must improve, it says, and there is a pressing need to develop antivirals and vaccines for RNA respiratory viruses. Other than for influenza, there are no highly effective antivirals against RNA respiratory viruses, and no vaccines against RNA respiratory viruses – including flu – are highly efficacious. “Ongoing efforts to create a universal flu vaccine should continue and be supplemented, given the risk of a novel influenza A virus to cause a GCBR,” the authors argue.

Of course, controversy dogs some vaccines, notably the purported links between MMR and autism, and between the HPV jab and serious adverse events, which pharmacists can help dispel. After all, as the Proceedings of the National Academy of Sciences notes, vaccines are “some of the most effective and also costeffective prevention tools we have”.4

 

Fact file

  • The chances of surviving cancer rose markedly between 1971-2011
  • Age-standardised mortality from cardiovascular disease fell by 75 per cent between 1969 and 2015
  • Antivirals raise the realistic prospect of eradicating hepatitis C virus (HCV) infections.

Cancer therapeutics

Everyone knows a friend, family member or colleague who has had cancer. Indeed, malignancies are increasingly common, partly because, on average, we live longer. Nevertheless, the chances of surviving cancer rose markedly between 1971-2011.

In England, half of those diagnosed with cancer in 1971-72 lived for a year after diagnosis. For those diagnosed with cancer in 2005- 6, half lived for five years. Researchers predict that for patients diagnosed during 2010-11, half will survive 10 years after diagnosis.

Nevertheless, outcomes vary widely. It is estimated that 98.2 per cent of patients diagnosed with testicular cancer during 2010-11 will survive 10 years after diagnosis. This compares to just 1.1 per cent of those diagnosed with pancreatic cancer.5

All areas of cancer care – from screening to palliative care – have improved dramatically. Technological advances, better after-care and improved rehabilitation have improved surgical outcomes. Radiotherapists can now target x-rays to the tumour with unprecedented accuracy and can vary the focus and intensity of the x-ray beam to match the cancer’s shape and density.

Chemotherapy has a poor reputation, largely due to the potentially debilitating side-effects, but it does cure some cancers. Vincristine, for example, has improved the chances of surviving childhood leukaemia from less than 10 per cent in 1960 to more than 90 per cent today. Chemotherapy cures 95 per cent of testicular cancers that have a good prognosis and 40-60 per cent of advanced Hodgkin’s lymphomas.

Other pharmacological approaches have transformed the prospects for certain cancers. Targeted treatments can influence specific processes that control the growth, division, spread and death of cancer cells. Some targeted therapies block growth factors (biological messengers that promote the cancer’s progression).

Trastuzumab, for example, targets human epidermal growth factor receptor 2 (HER2). In a study of 4,046 women whose breast cancers over-expressed HER2, trastuzumab added to chemotherapy increased overall survival during a median follow-up of 8.4 years by 37 per cent and disease-free survival by 40 per cent compared to chemotherapy alone.6

Meanwhile, immunotherapy, which leverages the immune system’s power to tackle cancer, is one of the most active and promising areas in cancer research. Therapeutic vaccines, for example, stimulate the immune system to attack and destroy certain malignancies.

In some cases, doctors use samples of the cancer to develop patient-specific vaccines. Other ‘non-individualised’ vaccines target a specific protein expressed by the cancer but not healthy tissue.

Another approach to immunotherapy uses viruses that replicate in and kill cancer cells and not healthy tissue. These ‘oncolytic viruses’ reduce the size of the tumour and trigger the body’s immune responses against the cancer. As a final example, some drugs block the checkpoints in the pathways that inhibit the immune response against the cancer, essentially, ‘reawakening’ immune cells inside the cancer.

Cardiovascular drugs

According to the British Heart Foundation, age-standardised mortality in the UK from cardiovascular disease fell by 75 per cent between 1969 (1,045 per 100,000) and 2015 (260 per 100,000). During the same time period, deaths from strokes fell by 79 per cent (from 301 to 64 per 100,000). Drugs made an important contribution to this decline.

Between 1981 and 2000, for example, age-specific mortality from coronary heart disease (CHD) in England and Wales fell by 62 per cent in men and 45 per cent in women aged 25-84 years of age. Statistical analysis suggested that medical and surgical treatments accounted for 42 per cent of this decrease.7

Reduction in cardiovascular risk factors – mainly smoking, raised cholesterol and hypertension – accounted for the remaining 58 per cent. In people with established CHD, medical and surgical treatments accounted for 78 per cent of the decrease.7

Increasing levels of diabetes, obesity and physical inactivity mean that the reduction is not as marked as it might be. Nevertheless, primary prevention in healthy people was responsible for 81 per cent of the decrease in CHD mortality between 1981 and 2000, with secondary prevention accounted for the remainder.7 Community pharmacists need to keep stressing the importance of primary prevention.

MS: Disease modifying therapies

Although one person in every 600 in the UK lives with multiple sclerosis (MS), the disease remains poorly understood, enigmatic and incurable. Nevertheless, a growing number of disease modifying therapies (DMT) has transformed the prospects for many people with MS, reducing the frequency of relapses and, in some cases, delaying disability.

For instance, researchers from the US followed 517 “actively managed” patients for a median of 16.8 years after MS onset. Previous studies had found that up to 54 per cent of people with relapsing MS transitioned to secondary progressive MS (SPMS) after a median of 19 years, leading the authors to conclude that between 36 and 50 per cent of the relapsing MS patients would have developed SPMS during the 16.8-year follow-up. In the study, however, only 18.1 per cent moved from relapsing to SPMS.8

A Norwegian study of 1,388 MS patients diagnosed between 1953 and 2012 found that life expectancy was, on average, seven years shorter in people with MS than the general population. Mortality was 2.4 times higher in those with relapsing-remitting MS and 3.9 times higher in those with primary progressive MS.

However, survival rose throughout follow-up. “The rapid development of new disease therapies in MS and overall improved caretaking of the disabled during the last decades are thus promising for future improvements of survival and life expectancy in MS,” the authors comment.9

If anything, these results may underestimate DMT’s benefits. Treatment continues to advance considerably, exemplified by the recent launch of ocrelizumab, the first disease modifying therapy for primary progressive MS. Neurologists are also learning how to sequence the disease modifying drugs and tailor particular medicines to individual patients.

Come a long way

As these examples show, we have come a long way since the start of the NHS in 1948. It is difficult to imagine a world without effective treatments for MS, HIV and many cancers… and there are plenty of other examples. We have not touched on asthma, psychiatric diseases and antibiotics (penicillin was introduced during the Second World War and so misses our cut-off).

Over the next 70 years, the NHS will face many more challenges. As we have seen, certain cancers still have a dismal prognosis, the risk of a global catastrophic biological risk will persist at a time when the problem of antimicrobial resistance continues to rise, and we desperately need a breakthrough in dementia as more people live for longer with chronic illness. Will pharmaceutical and medical science rise to the task? Let us hope so.

 

References
1. European Journal of Immunology 2007; 37:S94-S102
2. The Lancet Public Health 2017; 2:e35-e46
3. Proceedings of the National Academy of Sciences 2014; 111:12283-12287
4. Proceedings of the National Academy of Sciences 2017; 114:4031-4033
5. The Lancet 2015; 385:1206-1218
6. J Clin Oncol 2014; 32:3744-52
7. BMJ : British Medical Journal 2005; 331: 614-614
8. Annals of Neurology 2016; 80:499-510
9. Journal of Neurology, Neurosurgery & Psychiatry 2017; 88:621-625

Originally Published by Pharmacy Magazine

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