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Psoriatic arthritis could be prevented with rheumatologic agents in psoriasis treatment

In his presentation to the ISR 2016 Autumn Meeting, Prof Dennis McGonagle said there was evidence for psoriasis therapy to be used as a potential preventative therapy for PsA.

Prof McGonagle told the Medical Independent (MI) after his presentation that many medications used to treat psoriasis have no benefit in treating arthritis. 

“There are many drugs used to treat psoriasis, including topical agents and UV therapy based-drugs,” he explained.

“There is no evidence they would help the joints. But there are some animal models that say if you cure the skin you might help the joints, but that doesn’t appear to be the case in man. Some of the drugs used in dermatology systemically, including cyclosporine, don’t have much evidence for working in arthritis.  The vitamin A analogue acitretin is used to treat skin but it has no evidence for being effective in the joint. There are also fumaric acid esters, which are popular in Europe and now coming to the British Isles, but there is no evidence these work in the joints either.”

However, there is some evidence that drugs such as methotrexate, used to treat severe psoriasis and also arthritis, could be of benefit for preventing the development of PsA.

“There is no detailed study yet looking to ascertain whether treating skin disease for skin’s sake with methotrexate might prevent arthritis development,” according to Prof McGonagle.

“There are some small ultrasound studies saying that methotrexate may regress the sub-clinical entheseal abnormalities. The drug apremilast also has a license for both psoriasis and psoriatic arthritis, and in psoriatic arthritis it does have efficacy data for isolated enthesitis. So that might be a small molecule taken systemically that could theoretically prevent arthritis. Finally, all of the biologics available, the anti-TNF class, the anti-IL-12/23 ustekinumab, and the anti-IL-17s, all of these agents have licenses independently for skin disease, so you would expect that they should prevent arthritis development.”

Prof McGonagle said exploring the benefits of preventing the development of arthritis in psoriasis patients should be part of a move towards a holistic approach to treating this group.

“The problem is that in psoriasis clinics, a third of patients — if you do a questionnaire — will admit to having joint symptoms. 

“But most of those symptoms are likely to be osteoarthritis or mechanical problems. So in the UK, for example, if every patient with psoriasis was asked ‘how are your joints?’ and they were sent to see a rheumatologist, that would generate four or five thousand extra medical consults a year. I don’t think that is feasible. What I think we need to be aware of in patients with psoriasis is if they have any joint pains, rather than investigating it, which is difficult to prove, whether it is inflammatory or mechanical pain anyway, because osteoarthritis can also cause entheseal abnormalities, I would recommend that dermatologists should be aware that arthritis is a comorbidity that may develop. They should do a questionnaire and ask about joint symptoms, and if the patient has symptoms, they select an agent that treats skin and may prevent joint disease.”

Meanwhile, Dr Bruce Kirkham, Consultant Rheumatologist at Guy’s and St Thomas Foundation Trust, UK, spoke about mechanism of action developments and potential targets for IL 17. 

Dr Kirkham’s presentation included details of recent clinical trial data, such as the FUTURE 1 and 2 trials, which examined the benefits of secukinumab, which is a human anti-IL-17A monoclonal antibody, in PsA.

FUTURE 2 showed improvements with subcutaneous secukinumab 300mg and 150mg were sustained over one year of treatment in the majority of patients (64 per cent for both doses), as measured by the American College of Rheumatology (ACR) response criteria.

Moreover, ACR 50 response rates were also sustained to one year in secukinumab 300mg and 150mg (44 per cent and 39 per cent respectively). 

Secukinumab met the primary endpoint of the study, which was ACR 20 at week 24, with response rates significantly higher in the secukinumab 300mg (54 per cent) and 150mg (51 per cent) groups versus placebo (15 per cent), with clinical improvements observed as early as week three. ACR 20 and 50 are standard tools used to assess improvement of PsA signs and symptoms, and represent a 20 per cent and 50 per cent improvement from baseline, respectively.

Although the secukinumab benefits seen in FUTURE 2 were generally higher in patients without previous treatment with standard of care anti-TNF therapy, clinical benefits were observed in both anti-TNF-naïve patients and those with an inadequate response to anti-TNFs.

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