Abbott’s annual Collaborative Biologics Forum is unique in Ireland, being the only meeting to bring together doctors from different specialties with similar treatment possibilities. The rapid advances in biologics such as TNF inhibitors and the benefits they bring to patients in dermatology, rheumatology and gastroenterology means the meeting becomes more relevant every year.
This year’s Forum, co-chaired by Dr Richard Farrell, Dr Brian Kirby and Dr Barry O’ Shea, held in Dublin recently, focused on managing co-morbidities in psoriasis patients; anti-TNF therapies post-surgery; and new goals in treating patients with rheumatoid arthritis. The meeting also heard from Professor Michael Barry, consultant clinical pharmacologist and Clinical Director of the National Centre for Pharmacoeconomics, who spoke about emerging issues in relation to assessing the cost effectiveness of medicines and technologies.
Psoriasis
Professor Wolf-Henning Boehncke, consultant dermatologist, Frankfurt, Germany and newly appointed Head of the UCD Charles Institute for Dermatology, spoke about managing co-morbidities in psoriasis, such as psoriatic arthritis and Crohn’s disease and the increasing problems associated with the metabolic syndrome. He also described why severe psoriasis can be considered as an independent risk factor for cardiovascular disease.
He explained that Crohn’s disease is one of the biggest co-morbidities in psoriasis patients. In a recent study of 12,502 psoriasis sufferers, researchers found they were two-and-a-half times more likely to have Crohn’s disease. Prof Boehncke said that the genetic reasons for this link are being explored.
“My understanding is there are some polymorphisms within the IL-12 gene that seem to infer an increased risk of psoriasis and also of Crohn’s disease,” he said.
He highlighted the clinical importance of T-helper 17 (Th17) cells, a T-cell subset distinct from both Th1 and Th2 cells that have now been implicated in the pathogenesis of psoriasis and other autoimmune inflammatory diseases.
Several studies have demonstrated an important role of Th17 cells in intestinal inflammation, particularly in Crohn’s disease, said Prof Boehncke.
Prof Boehncke explained that studies have implicated IL-17, which is released by a subset of memory Th17 cells that are stimulated by IL-23, as a mechanistic link between T-cell activation and inflammation. In contrast to normal skin, IL-17 is expressed in psoriatic skin lesions.
“IL-17 is also found in the inflamed joints of patients with rheumatoid arthritis (RA) and Lyme disease, as well as foci in inflammatory bowel disease, multiple sclerosis, collagen-induced arthritis, and ischaemic stroke. Notably, IL-17 is also seen at higher levels, along with IL-6, IL-8, and C-reactive protein, in the plasma of patients who have suffered unstable angina and acute MI.”
This led Prof Boehncke to discuss other important co-morbidities, which include metabolic syndrome and cardiovascular problems.
“The concern that psoriasis and rheumatoid arthritis patients face a higher risk of premature cardiovascular mortality than others of the same age and background may be explained by the fact that the cell-mediated immune dysregulation associated with heart disease is already markedly elevated at baseline in patients with T-cell mediated diseases,” said Prof Boehncke.
There has historically been a “heated debate” over the issue of cardiovascular risk factors in psoriasis patients, but Prof Boehncke believes that the link is clearly evident.
“We know that once psoriasis patients are treated they improve their vascular elasticity – systemic anti-inflammatory therapy will have an effect on cardiovascular disease co-morbidity.”
Prof Boehncke described rheumatologists as being better than their colleagues in dermatology when it comes to defining treatment goals.
“I believe we under-treat our patients in dermatology because we are concentrating only on their skin symptoms, and not assessing the systemic burden of our patients,” he said. “It’s really important that our patients are much more comprehensively managed.”
Anti-TNF and the surgical patient
Professor Jacques Cosnes, consultant gastroenterologist at Hopital St-Antoine, Paris, France, next discussed whether Crohn’s disease patients receiving anti-TNF therapy have a decreased need for surgery later in life.
“Almost all patients with Crohn’s disease, which is very progressive, will need surgery at some point. Surgery is not curative, so disease will recur, and about one-third will need to be re-operated on in about 10 years,” said the professor.
Studies show that some 60 per cent of Crohn’s patients with moderate to severe disease show improvement on anti-TNF-alpha medications, with on average 43 per cent achieving remission.
Numerous trials have looked at patients with Crohn’s disease on TNF inhibitors to compare them to those not taking this therapy. One such study found that one year after anti-TNF therapy, major surgery was only necessary in about four per cent of patients.
“There is slightly conflicting data on surgery post anti-TNF therapy,” said Prof Cosnes, “but it should be pointed out that in some of these studies differing patient populations were used. So comparing them can be difficult.”
In summary, Prof Cosnes said that anti-TNF therapies are effective for preventing recurrence in most patients with Crohn’s disease.
There is “some recent decrease” in the need for surgery in Crohn’s disease, Prof Cosnes summarised, saying that he believes the use of anti-TNF is probably in part, at least, responsible for this decrease.
“In our practice, we consider the use of anti-TNF as prevention in some patients. These agents do result in some decrease in surgery. I believe our therapeutic strategy should focus on using anti-TNF therapies and immunosuppressive therapies earlier and earlier in the course of the disease. I think this will lead to a progressive decline in surgery,” the professor concluded.
Sustained remission in RA
Dr Barry O’Shea, consultant rheumatologist in St James’s Hospital, Dublin, next spoke about inducing sustained remission in RA, which is the aim of therapy when treating the disease according to the newest recommendations from the European League Against Rheumatism (EULAR) .
“We need to get to patients earlier and diagnose earlier. New diagnostic criteria outline that we should be ‘treating to target’ – meaning our goal is disease remission,” said Dr O’Shea.
“In many other areas of medicine, treatment targets have been defined to improve outcomes, leading to a reduction in the risk of organ damage. In patients with diabetes, for example, these aspects have been adopted widely in practice; doctors order laboratory tests for cholesterol and triglycerides, blood glucose and HbA1c levels, check blood pressure and adapt therapy accordingly, and patients know these values and are aware of the treatment targets.”
According to the EULAR RA Treat to Target guidelines, which were published last year in the Annals of the Rheumatic Diseases, the four main principles of treating to target are: Treatment should be a shared decision between the rheumatologist and the patient; the primary goal is to maximise HRQoL; abrogation of inflammation is key to achieving this; and doctors should treat to target by managing disease activity and altering medication accordingly.
“Traditionally, with the older ‘treatment pyramid’ for RA – in which older therapies were tried first, moving up the scale until the newer therapies were tried if the older ones failed-- the majority of patients failed to ever reach remission. In this (older) pyramid, how it worked was, we started at the bottom and worked our way up. This pyramid has now been turned on its head,” said Dr O’Shea. “The advent of biologic therapies has drastically changed things.”
According to the mechanism of action, Dr O’Shea explained, these drugs include: the anti-TNF drugs (adalimumab, etanercept, infliximab, golimumab, certolizumab); IL-6 blocking drugs (tocilizumab); agents blocking selective co-stimulation modulation (abatacept); and CD-20 blocking drugs (rituximab).
“Biologics targeting TNF-alpha with methotrexate have revolutionised the treatment of RA, producing significant improvement in clinical, radiographic, and functional outcomes not seen previously.”
Finally, he said that new research is focusing on the exploration and use of biomarkers in RA. Other exciting developments include studies presented this year at EULAR, which showed the potential of using power Doppler and ultrasound to determine which patients may achieve disease remission.
Assessing the value of medicines
Prof Barry closed the event by outlining some of the changes taking place internationally with regard to assessing the value of medicines and technologies.
He explained that there is a drive in the UK to move to a system of “value- based pricing” assessments, and from 2014 on NICE guidance will no longer be mandatory.
“The question being asked is what we are willing to pay for healthcare?” asked Prof Barry.
He said the NCPE have conducted a mixed-treatment comparison examining the effectiveness of anti-TNF agents in RA, finding that the overlap between the products was so substantial that they could not say one anti-TNF is “better” than another in terms of cost-effectiveness.
This report is published in association with Abbott
References on request
