A licence to cureBMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h1723 (Published 01 April 2015) Cite this as: BMJ 2015;350:h1723
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Monitoring of quality of life of patient and risk benefit is needed before considering off label prescription
Monoclonal antibodies (mAbs) are established therapies for malignancies, transplant rejection, autoimmune and infectious diseases, as well as a range of new indications. However, a series of adverse effects are listed with their use. Some of them such as immune reactions, acute anaphylaxis, cardiotoxicity, life-threatening cytokine release syndrome, serum sickness are life threatening.
Numerous adverse effects of mAbs are related to their specific targets and include ranges of complaints from patients. More common are Black, tarry stools, bleeding gums, body aches or pain, burning, tingling, numbness, or pain in the hands, arms, feet, or legs, chest pain or discomfort, chills, cloudy urine, convulsions, cough, cracks in the skin, decreased urine output, difficult or labored breathing, dilated neck veins, dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position, ear congestion, extreme fatigue, fever, irregular breathing, irregular heartbeat, lack or loss of strength, lightheadedness, loss of appetite, loss of heat from the body, loss of voice, mood changes, nasal congestion, nervousness, pain, pain, redness, or swelling in the arm or leg, painful or difficult urination, pinpoint red spots on the skin, pounding in the ears, rapid breathing, redness, runny nose, sensation of pins and needles, slow or fast heartbeat, sore throat, weight gain, swollen glands, tightness in the chest.
Some less common side effects are difficulty with swallowing, fainting, severe constipation, severe vomiting, blisters, blurred vision, coma, Gastrointestinal perforations, wound healing complications, hemorrhage, hypertension, proteinuria, CHF, infusion-related reactions, immunogenicity and are common with Avastin (Bevacizumab).
While it requires quite vigorous supervision and strict monitoring in well approved conditions, and in view of the above scenario, it should be carefully evaluated not merely for survival benefits but for the quality of life of patients before off label prescription.
Nature Reviews Drug Discovery 9, 325–338 (1 April 2010)
Preclinical and clinical safety of monoclonal antibodies. Mohammad A. Tabriz, Lorin K. Roskos, Drug Discovery Today. Volume 12, Issues 13–14, July 2007, Pages 540–547
Competing interests: No competing interests
After substantial effort by many people, over a long period of time ; the completion of two substantial RCTs and much lobbying it is a fact that patients are still nearing the opportunity cost of lucentis and eylea being the drug of choice in AMD and other conditions.
This opportunity cost manifests itself as poorer quality of care, less care and no care. Those that bear the opportunity cost are anonymous, and may have any condition, in this respect the investment in aVEGF are depriving patients with cardiovascular or musculoskeletal disease of the best possible care.
One must question whether the unfairness and inequity this causes is acceptable.
The evidence is clear. Lucentis and avastin are equally efficacious and safe in AMD and probably DMO . In the minds of many all the available agents are equally effective, there is growing evidence of this. There is good evidence of equivalent safety .
Maintaining the current status quo is unfair and inequitable. It seems unlikely that any national agency will resolve this anytime soon. There are four burning questions that each CCG should ask of their Ophthalmology dept
1. Give the Cochrane review, do you really think the "it's not safe" argument is credible
2. What do you prescribe to private patients
3. Send us your justification for denying others treatment if you still use lucentis or eylea as a first line agent.
4. in the spirit of openness and complete transparency, please be open about how much funding your hospital, department and individual clinicians have received from companies with a stake in this market; in cash or in kind.
It seems unfair to expect patients with other diseases (so say, less investment in MSK, Gastro or dermatology) to foot the bill (for ever growing ophthalmology drug bill) by way of less good care, less investment and maybe service cuts.
It's unfair and inequitable to expect patients with cataract or glaucoma to foot the bill for ever increasing growth in aVEGF areas also. Continuation of this is inequitable and unfair. It's also inefficient and leads to net social loss.
Nobody disputes that lucentis is effective. Its just there is a cheaper and equally effective alternative.
Competing interests: I have participated in an Advisory Board for Bayer HealthCare for which my employer was reimbursed for my time.
Aronson and Ferner (1) have highlighted a very ugly feature of pharmaceutical industry. It was shocking to learn that use of propranolol (Haemangeol) to treat haemangiomas will cost 40 times more than the cheapest available oral solution of propranolol. How could a drug which has been around for nearly 50 years be patented afresh for a particular indication ?
A comparison would be if a manufacturer of umbrellas patents their use as a sun block !
Clearly the patent system is broken and needs to be fixed. Alternatively, governments should bring about a legislation preventing drug companies from charging extortionate prices on drugs without full explanation about production cost.
Ideally pricing of drugs should be agreed between drug companies and a government body or a price regulator. Such bodies do exist for other utilities such as electricity or mobile phones, where a pricing formula is agreed so that the companies can make a reasonable profit. Why should medicines be left out ?
Reference: Aronson JK, Ferner RE. A licence to cure. BMJ 2015; 350: h1723.
Competing interests: No competing interests
The "licensing" process works quite well to protect patients from pharmaceutical companies promoting ineffective or unsafe products. This regulatory system is not intended to and nor should it, regulate clinical practice. In the UK the GMC has taken a position that uses the industry regulation system and applied it to clinical practice, thus discouraging if not essentially forbidding, clinicians from prescribing safe and effective products but for which the drug companies, for profit reasons, have not applied for a marketing authorisation. The regulatory system (the province of the MHRA and EMA) does not need changing for this purpose. It is the GMC that must first change, and then NICE (not bound in law to only recommend products in indications where there is a marketing authorisation- MA) can make untrammelled decisions on cost-effective products. It has had pressure to restrict advice to products with an MA but it does not need to do so. Change GMC advice first, then change NICE advice, based on good evidence. The sad thing is that the pharmaceutical industry continues to damage its public reputation by opposing this thinking.
Competing interests: I am a European Commission appointed Independent Expert Member of the Pharmacovigilance and Risk Assessment Committee at the European Medicines Agency which assesses safety of drugs and vaccines that are marketed in the EU.