Denosumab reduces glucocorticoid-induced bone loss

About one in every 100 people in the world takes glucocorticoids long term to treat immune-mediated diseases. However, glucocorticoids, such as prednisone, have a side effect — they induce the bone loss called osteoporosis, causing an estimated yearly bone fracture rate of 5 percent.

An alternative treatment option now appears promising. The study was headed by Dr Kenneth Saag, the Jane Knight Lowe Professor of Medicine at the University of Alabama at Birmingham.

Denosumab could be a useful addition to the treatment armamentarium for glucocorticoid-induced osteoporosis

Dr Saag and colleagues compared the monoclonal antibody denosumab against a standard treatment for glucocorticoid-induced secondary osteoporosis, the bisphosphonate risedronate. In the 12-month results of their 24-month study, they have found that denosumab was superior to risedronate, as measured by increased bone density in the lower spine.

"To our knowledge, ours is the first large, randomised controlled trial of denosumab in patients with glucocorticoid-induced osteoporosis who were either prevalent glucocorticoid users or newly initiating glucocorticoid therapy," they wrote. "Denosumab could be a useful addition to the treatment armamentarium for glucocorticoid-induced osteoporosis."

The double-blind study enrolled 795 patients at 79 health care centres in Europe, Latin America, Asia and North America. Of these, 505 were glucocorticoid-continuing patients who had received glucocorticoids for at least three months, and 290 were glucocorticoid-initiating patients who had received glucocorticoids for less than three months.

Patients were randomly assigned to one of two groups. The denosumab group got a shot of denosumab underneath the skin every six months and took a placebo pill every day. The risedronate group got a placebo shot every six months and took oral risedronate every day.

Besides the superior lumbar spine bone density with denosumab after 12 months, researchers also found that denosumab was superior to risedronate for bone density measured in the total hip and at the neck of the femur, the large bone of the thigh.

The two treatment groups had similar safety profiles.

The researchers note that the study compared denosumab with risedronate, so the relative performance of denosumab compared with osteoporosis treatments besides risedronate has not yet been established.

The study has been published in the journal The Lancet Diabetes & Endocrinology.

NHS England chief executive Simon Stevens has indicated that chimeric antigen receptor T-cell therapy (CAR-T) could be available on the NHS this year, offering eligible patients a ‘ground-breaking’ approach to treating cancer.

Addressing the Association of the British Pharmaceutical Industry’s annual conference in London, he said "preparations are underway to make CAR-T, one of the most innovative treatments that has ever been offered on the NHS available to patients."

But he also stressed manufacturers "need to set fair and affordable prices so treatments can be made available to all who need them."

"This is a really positive step for some people living with cancer whose lives cannot be saved using the treatments doctors can already provide," said Dr Alasdair Rankin, director of research at the leading UK blood cancer charity Bloodwise, welcoming the announcement.

However, he also cautioned: "These therapies are expensive, and in order for them to become widely available, manufacturers need to set fair prices so that they are both affordable and sustainable in the long term."

CAR-T therapy offers a new treatment approach in that it is specifically manufactured for each individual patient. During the process, T cells are drawn from a patient's blood and reprogrammed in the lab to create T cells that are genetically coded to hunt the patient's cancer cells.

The first CAR-T therapy is yet to be approved in Europe, but a regulatory green light will only be the first hurdle to securing patient access; while they are effective, the therapies are expected to be very expensive and are complicated to administer.

"There is a whole body of work being done to draw up service specifications for centres in the UK at NHS hospitals to determine what the requirements are to deliver this kind of therapy to patients, because they are very complex," Emma Morris, professor of clinical cell and gene therapy at University College London, told the Guardian.

"Currently we are only delivering them [in clinical trials] in two or three centres in the UK and run by transplant teams used to giving cell therapies."

Kite Pharma submitted the first CAR-T cell therapy for review in Europe, seeking permission to market its axicabtagene ciloleucel (axi-cel) to treat patients with three subtypes of aggressive non-Hodgkin lymphoma (NHL).

EU regulators are also reviewing Novartis’ CAR-T therapy CTL019 (tisagenlecleucel) for children and young adults with relapsed or refractory (r/r) B-cell acute lymphoblastic leukaemia (ALL) and for adult patients with r/r diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant.

"As we celebrate the 70th anniversary, the NHS is working harder than ever to save lives and improve care by embracing cutting edge technology like CAR-T therapy and spreading innovation across the whole health service," Stevens said.

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