I don’t intend to embark on a discussion of overprescription and the use of dangerous drugs in an inappropriate way (although I did read a piece that incensed me, about why patients with RA should not receive methotrexate because we rheumatologists dish it out with gay abandon). Rather I want to discuss why some drugs are denied to patients by non-clinicians (or non-specialists) because of financial considerations alone.
In my long experience of dealing with applications to use drugs – and these are always for highly specialist things that almost always cost lots of money – I have encountered managers and clinicians who fall into two groups. There are those who take a pragmatic, and to my mind sensible approach, which is that if a clinician submits a detailed application there must be a good reason, and thus errs on the side of agreeing. There are also those who are jobsworths, and shelter behind detailed guidelines to find any excuse to avoid allowing use of something expensive while not always having any reasonable clinical argument to back up their decision.
Certolizumab is a case in point. It is a biologic therapy – a tumour necrosis factor antibody used in the management of severe rheumatoid arthritis. Because it is one of a family of TNF antagonists it has been treated as identical to the others available (infliximab, adalimumab and etanercept). A deal done by the manufacturers offered a free 3 month trial of certolizumab; as a result, some GP managers and therapeutics committee members decided that it should be the first choice TNF antagonist because of the cost saving (also it was presumed that TNF failure at 3 months was the end of the line for that particular treatment).
However this decision failed to account for several factors.
- The mechanism of action of the TNF antagonists is not physiologically identical, and there is therefore no reason to believe they should produce identical clinical effects. Antagonists ending in “ab” are antibodies against TNF but the human immune system can and does produce antibodies against them. Those ending in “cept” are fake TNF which blocks the receptor sites on cells.
- There are differences in side-effects (not fully detailed, but it appears that the “ab’s” have more serious respiratory side-effects than the “cepts”)
- It is never clear whether new “me-too” drugs will have exactly the same profile as the old ones, either in efficacy or side-effects
- It’s all very well comparing two drugs each against placebo and inferring they have similar efficacy, but without a head-to-head trial the verdict remains not proven, as the Scottish courts would have
So one must conclude that the evidence on which a decision to use certolizumab first, even though there is much less clinical experience of it, was not clinical evidence. Cost is the prime mover.
Another example is the use of Infliximab in Behçets disease – an uncommon but disabling condition characterised by nasty skin lesions (including involvement of the mucous membranes of the mouth and genital area) and an arthritis. I had one such patient whose disease responded dramatically to Methotrexate, but she developed serious side-effects. So we had to terminate the treatment and she had a major relapse.
She had already received all the standard starting therapy, so we were at a dead end. I was not going to use thalidomide, for which there was trial evidence of benefit, because of her age and the possibility of her becoming pregnant. There were two case reports of dramatic benefit from Infliximab given as a short course.
I applied through the local vetting committee for permission to proceed. It refused on the grounds that there were no clinical trials and that anecdotal evidence was not good enough. I could however use thalidomide…
So I was faced with a patient in serious trouble, but forbidden to use a safe drug and offered the ridiculous option of a seriously dangerous one that was, it seemed to me, mad to consider in a young lady. I fear I lost my temper as well as the battle. The patient moved away, having lost her job because of her disease, so I don’t know what happened to her. However in the intervening three years – guess what? Following up on the anecdotes a trial was done. It confirmed benefit. For the want of a nail…
At the end of 2012, some four years after this shameful episode, I learned at a rheumatology meeting some of the details of a new scheme to develop specialist centres for Behçet’s patients. All you now have to do to get authorisation for infliximab (which unsurprisingly has now been shown all over the place to work like magic) is discuss the case with one of the centre specialists and they will rubber-stamp it. There’s nothing worse than being ahead of one’s time.
And there was a third shameful jobsworth episode. A patient of mine with ankylosing spondylitis had, off her own bat, got herself funding for residential rehabilitation at the Royal National Hospital for Rheumatic Diseases in Bath. While there she had been entered into a trial of TNF blockade, and had been on treatment for three years. At this time the biologic drugs had not been approved by NICE for use in AS, so when the trial came to an end I applied for individual funding from her Primary Care Trust. This was refused. She was devastated as she saw that her condition would slide inexorably backwards. The refusal seemed to me to be both uncharitable and stupid. I knew that NICE had already issued draft approval and it was only a matter of time before full approval was confirmed. After that the PCT was legally obliged to cough up. But it stuck to its jobsworth principles, claiming that draft approval wasn’t good enough. Having had considerable experience of NICE decisions I knew that the only ones that got disputed were those that NICE had turned down. For the sake of a few weeks, maybe months, the PCT was prepared to make my patient suffer.
However she did not take this lying down. Instead she went to the regional television news, made her case, got the media firmly on her side (I added a bit of gravitas), caused a major public fuss and got her treatment. I still find it hard to understand the inflexibility of the PCT in the circumstances, but it all caused her, and me, considerable annoyance and inconvenience.