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Take a look at a selection of our recent media coverage:

MHRA approves bimekizumab for psoriatic arthritis and axial spondyloarthritis

31st August 2023

Bimekizumab is now approved for use by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) for the treatment of adults with active psoriatic arthritis (PsA) and active axial spondyloarthritis (axSpA), its manufacturer UCB has announced.

The MHRA approval of bimekizumab (brand name Bimzelx) makes the drug the first approved treatment both both conditions that works as a dual IL-17A and IL-17F inhibitor, both of which have ben implicated in driving the inflammatory processes associated with PsA and axSpA.

Bimekizumab can be used alone or in combination with methotrexate, for the treatment of adults with active PsA who have had an inadequate response or who have been intolerant to one or more disease-modifying anti-rheumatic drugs.

The AxSpA indication spans both non-radiographic axSpA (nr-axSpA) and ankylosing spondylitis (AS), also known as radiographic axSpA (r-axSpA).

For adults with nr-axSpA, bimekizumab can be used where there are objective signs of inflammation, as indicated by elevated C-reactive protein and/or magnetic resonance imaging, or for those who have responded inadequately or are intolerant to non-steroidal anti-inflammatory drugs. It can also be used for the treatment of adults with active r-axSpA who have responded inadequately or are intolerant to conventional therapy.

Claire Brading, managing director UK and Ireland at UCB, said: ‘The approval of Bimzelx in psoriatic arthritis and axial spondyloarthritis is a significant milestone for the rheumatology community in the UK.‘

She added: ‘We are extremely proud to be able to bring a new dual action biological treatment option to a broad range of people living with psoriatic arthritis and axial spondyloarthritis in the UK.‘

Bimekizumab clinical efficacy

The MHRA approval for use in PsA was based on the findings of two randomised, double-blind, placebo-controlled phase 3 trials, BE OPTIMAL and BE COMPLETE. In both studies, bimekizumab met the primary endpoint of a 50% or greater improvement in American College of Rheumatology criteria (ACR50) at week 16 and all ranked secondary endpoints.

Consistent results were seen across both biologic-naive and TNF-inhibitor (TNFi) inadequate responder populations and the clinical responses achieved at Week 16 were sustained up to Week 52 in BE OPTIMAL.

In addition, among biological DMARD-naive and TNFi patients with an inadequate response, 47% and 59% of patients with baseline psoriasis affecting ≥ 3% body surface area receiving bimekizumab achieved a PASI100 at Week 16, respectively compared to only 2% and 5% receiving placebo.

The approval for axSpA was also based on the findings of two phase 3 trials, BE MOBILE 1 (nr-axSpA) and BE MOBILE 2 (AS). Bimekizumab met the primary endpoint of Assessment of SpondyloArthritis international Society ≥40% improvement response at Week 16 compared to placebo and all ranked secondary endpoints.

Indeed, the drug showed improvements compared to placebo in signs, symptoms and disease activity across the spectrum of disease.

Commenting on bimekizumab’s approval, Professor Karl Gaffney, rheumatologist at the Norfolk and Norwich University NHS Foundation Trust, said: ‘Psoriatic arthritis and axial spondyloarthritis are chronic, painful conditions with no cure. The unfortunate reality for many patients is that they will have to cycle through a number of treatments before eventually finding one that works for them.

‘I welcome the possibility of a new, dual-action, biologic treatment option to potentially improve the quality of life of people living with psoriatic arthritis and axial spondyloarthritis.‘

Earlier this year, bimekizumab was found to provide clinical benefit in patients with moderate to severe hidradenitis suppurativa.

Psoriatic arthritis risk estimation tool reasonably accurate in psoriasis patients, study finds

14th August 2023

A psoriatic arthritis (PsA) risk estimate tool has been found to have a reasonable accuracy when used in patients with psoriasis and may lead to earlier diagnosis, according to a study by Canadian researchers.

A Canadian team have developed a multivariable Psoriatic Arthritis Risk Estimation Tool (PRESTO) for use in patients with psoriasis who are at high risk of PsA. The simple and scalable tool represents an important first step in the development and testing of interventional strategies that may ultimately halt PsA disease progression.

Previous recommendations by EULAR have highlighted points to consider the clinical and imaging features in psoriasis patients that are likely to result in the development of PsA, however, to date, there are no risk estimate prediction tools for the condition in use.

Psoriatic arthritis risk estimating tool

Initial findings from the tool were published in the journal Arthritis and Rheumatology.

Following exclusions for either PsA or other rheumatic conditions at baseline, a total of 635 patients with psoriasis were included in the study. From this total, 51 and 71 developed PsA during the one-year and five-year follow-up periods, respectively.

For the one-year model, the following variables were selected for prediction model: age, male sex, family history of psoriasis, morning back stiffness, nail pitting, stiffness level, use of biologic systemic medications, patient global health, pain (any level vs none).

All of these variables were associated with a higher risk of developing PsA except for age and patients’ global health, which were associated with a reduced risk. The discriminatory ability of the model was acceptable with an area under the curve (AUC) of 72.3% (95% CI 65.5 – 79.1).

The discriminatory ability of the five-year model was also acceptable, with an AUC of 74.9% (95% CI 69.3 – 80.5).

Lead author Lihi Eder, rheumatologist and associate professor at the Women’s College Hospital and the University of Toronto said: ‘The PRESTO tool could serve future efforts to reduce the progression from psoriasis to psoriatic arthritis. For example, PRESTO can be used to enrich prevention trials with at-risk populations.

‘It can also identify patients with psoriasis who can benefit from early treatments, and it can serve as an educational tool for patients to increase awareness of psoriatic arthritis risk. Ultimately, we hope that these efforts will improve the lives of people living with psoriatic disease.‘

The evolving management of psoriatic arthritis

10th August 2023

Dr Laura Coates, is an NIHR clinician scientist and senior clinical research fellow specialising in psoriatic arthritis at the University of Oxford. Here, she speaks to Rod Tucker about the management of psoriatic arthritis including diagnostic challenges, unmet needs and emerging treatments.

Laura Coates

Dr Laura Coates is a clinician and rheumatology researcher who completed her rheumatology training and PhD in the clinical management of psoriatic arthritis (PsA) at the University of Leeds in the Leeds Institute of Rheumatology and Musculoskeletal Medicine. Since 2017, she has worked at the University of Oxford where she leads the rheumatology research group, as well as the early arthritis and PsA service for the NHS.

Her main area of research is clinical, as opposed to laboratory-based, and her main focus is on PsA and the spondyloarthritides, including early diagnosis of PsA and optimal treatment pathways and strategies. She has been actively involved in clinical trials, the development of outcome measures for PsA and precision medicine.

While it is recognised that PsA affects up to 30 per cent of those with psoriasis and tends to occur around 10 years after the appearance of cutaneous symptoms, it can occur at any age. As Dr Coates explains, ‘I’ve had patients from their teens right up to their 80s who’ve developed a new psoriatic arthritis.’

Being an inflammatory-driven condition, treatment seeks to control the inflammation with immunomodulatory agents. While there is currently no known cure, PsA can often be adequately controlled with the right medication.

Diagnostic delays

Unfortunately, many patients experience a delay in receiving their PsA diagnosis. Quite why this is the case is not entirely clear, but Dr Coates believes that there are several possible reasons. Perhaps the biggest, she says, is because psoriasis patients are often unfamiliar with the fact that they are at a higher risk of developing PsA. ‘It would be great if more people with psoriasis were aware of that risk because they would know to seek help earlier and not just sit on it,’ she says.

Although research shows that PsA is more common in patients whose psoriasis is accompanied by either nail or scalp involvement, and there is a definite genetic link, many clinicians may not be aware of these associations. Moreover, far less is known about potential disease triggers, but, as Dr Coates points out: ‘A lot of patients remember a traumatic event, be that physical, like an operation or an injury, or psychological, like moving house or getting a divorce, around the time they developed PsA.’

A further and confounding diagnostic problem, for both patients and their primary care practitioners, is how PsA gives rise to a wide range of symptoms. Typically, most patients experience inflammatory symptoms, Dr Coates explains, but this can literally occur in any joint. In practice, she sees patients with PsA affecting either smaller joints, such as fingers and toes, or larger joints, such as the knees.

Alongside these inflammatory symptoms, up to half of PsA patients experience pain at the point where tendons insert onto the bone – typically the Achilles tendon. Nevertheless, for some, the diagnosis is much easier, particularly where patients present with dactylitis. This is characterised by whole digit swelling and is one of the major features of PsA, although this symptom can be quite variable and even resolve in some patients.

While there are no specific biomarkers for PsA, which further hampers the diagnosis, this might be set to change soon. Dr Coates’ team are about to embark on a European-wide study to monitor those with psoriasis and determine why some of these patients develop PsA. The aim is to enable an earlier intervention.

Another option to reduce the diagnostic delay is for more primary care screening with tools such as the Psoriasis Epidemiology Screening Tool (PEST), which has been recommended in the UK by the National Institute for Health and Care Excellence. However, Dr Coates doesn’t think that this practice is widespread, despite having some merit. ‘It’s not perfect and it can pick up other conditions such as osteoarthritis,’ she says. ‘I’d expect around a third of those with PEST scores that warrant referral do actually have PsA.’

Despite this low specificity, Dr Coates does see some value in screening because it enables rheumatologists to assess patients with a possible onward referral of those with osteoarthritis for physiotherapy, and is therefore ‘not a bad use of our time’.

In fact, in Oxford, the dermatology department routinely PEST screens everyone they see with psoriasis but selectively refers patients. For instance, Dr Coates describes how patients with higher PEST scores would only be referred to her department if they are bothered by joint symptoms.

Identifying unmet needs in psoriatic arthritis

In a recent priority setting partnership, both clinicians and patients came together to collectively identify areas of unmet need in PsA. This, Dr Coates says, raised a huge number of issues that require attention. For instance, both parties wanted to better understand how to enable earlier diagnosis of the condition and to ascertain if there were subgroups of patients that were more likely to develop PsA.

A further concern was the impact of co-morbidities, such as inflammatory bowel disease, uveitis and an elevated cardiovascular risk, which serve to increase the symptom burden in those with PsA and ultimately affect how the condition is managed.

But a particularly important area for both patients and clinicians was drug therapy, for which there are still many unknowns. As Dr Coates says: ‘We haven’t got a lot of evidence that tells us how to use them. We’ve got a lot of “drug A works better than placebo”, but not had a lot of comparative studies or strategies trials.’

A further uncertainty surrounds the prognosis of PsA, which can be highly variable. In those with significant disease, ‘about a quarter to half of patients will have radiographic damage despite treatment’, after two years, she explains. In contrast, for others with milder disease, PsA waxes and wanes and might only flare if, for example, they become stressed. As a result, while initiating therapy is those with troublesome disease is straightforward, it becomes much more difficult for those with less severe disease and those who only experience intermittent flares.

Treatment strategies

Among patients at the milder end of the disease spectrum, non-steroidal anti-inflammatory drugs and occasional intra-joint corticosteroids will often suffice. But where the disease becomes more bothersome, disease-modifying antirheumatic drug (DMARD) therapy, with drugs such as methotrexate, will be initiated. As it progresses further, and DMARDs fail to provide satisfactory control, rheumatologists can initiate biologic treatment. But whether or not conventional DMARDs, despite their widespread use, are effective in preventing radiographic damage is unclear.

‘There is limited data for conventional DMARDs on radiographic progression, hence proving that they prevent joint damage is harder,’ notes Dr Coates. In contrast, she describes how there is efficacy data showing that methotrexate reduces swelling and tender joint counts, and patient-reported outcomes, though the quality of the data isn’t particularly strong. But, for other DMARDs, the evidence base is much greater, and she mentions how the best trial data for conventional DMARDs is for newer agents such as leflunomide.

Guselkumab and psoriatic arthritis

There is a general consensus that interleukin-23 (IL-23) has an important pathophysiological role in PsA. This, combined with good data on the value of the IL-23 inhibitor guselkumab in patients with psoriasis, it seems reasonable to examine the drug in PsA. Research, such as the COSMOS trial, clearly shows that guselkumab is effective in PsA, and Dr Coates was recently involved in a post hoc analysis of trial data, which focused on minimal disease activity. In her analysis, Dr Coates looked at patient responses across different domains – skin, joints, enthesitis, pain, et cetera – and found that guselkumab gave rise to an ‘overall’ treatment response.

While PsA affects peripheral joints, the condition can also affect the spine, which is referred to as axial disease. Whether guselkumab is also effective for this form of the disease is still uncertain. Dr Coates says current evidence shows IL-23 inhibitors are ineffective for this phenotype, but, curiously, when patients were specifically asked about their spinal symptoms, they reported an improvement.

Dr Coates thinks there is a plausible explanation to account for this apparent discrepancy. It’s possible, she explains, that because the back pain questionnaires used are reasonably non-specific, the observed improvements in other domains, such as skin and joints, might have led patients to report an overall positive effect. In other words, a patient’s subjective response to the back pain questions is influenced by the other peripheral disease questions.

To better understand if guselkumab is effective in axial PsA, there is a specific trial in axial PsA underway that will involve magnetic resonance imaging scans. Using the imaging modality, researchers can obtain more definitive evidence of joint inflammation rather than damage, and this data can be used alongside the self-reported patient outcomes. 

Next steps in psoriatic arthritis management

With preliminary evidence showing that a combination of biologics may be more effective in hard-to-treat cases, this is an active line of current research, although as Dr Coates pointed out, there are potentially higher risks of infection. Consequently, clinicians need to be careful in the selection of which biologics to combine. There are more IL-17 inhibitors – another cytokine with a role in PsA – in the pipeline, with purported benefits such as greater albumin binding. However, Dr Coates is unsure if these purported differences will translate to a difference in clinical practice. Currently, the GRAPPA treatment recommendations consider drugs to be similar within class until there is evidence to the contrary.

Other agents on the horizon include TYK2 inhibitors as well as JAK inhibitors, and there are even nanobody IL-17 inhibitors in development, which may enable greater tissue and tendon penetration. Again, until there is evidence that this modification improves patient outcomes, there is no strong data to choose one drug over another within the same class.

There is little doubt that more treatments will become available for the treatment of PsA in the near future. Although Dr Coates agrees that a wider range of therapeutic options is invaluable for clinicians, gazing into the future, she would prefer to see more studies that focus on how best to use existing therapies and head-to-head trials with active comparators.

Moreover, she sees precision medicine as an equally important goal in PsA. If it becomes possible to utilise serum or tissue biomarkers, this will enable clinicians to tailor treatment and ultimately provide the best possible outcomes for the individual patient.

EULAR develops points to consider for psoriasis to psoriatic arthritis transition

19th July 2023

A series of points to consider to help define the clinical and imaging features of people with psoriasis who transition to psoriatic arthritis (PsA) have been developed by the European Alliance of Associations for Rheumatology (EULAR) in order to identify those who might benefit from a therapeutic intervention.

The fact that psoriasis typically develops some 10 years before PsA, provides an opportunity for clinicians to investigate risk factors and predictors for PsA in those with the skin disease. Now, with the help of both dermatologists and rheumatologists, a EULAR multidisciplinary taskforce of 30 members and from 13 European countries has produced five overarching principles and a total of 10 points to consider.

Published in the Annals of the Rheumatic Diseases, these principles acknowledge that not everyone with psoriasis will go on to develop PsA, and even among those who do develop the arthritis, this can occur at different times. The taskforce also stress the importance of being able to identify specific risk factors for PsA and how these could influence the choice of treatment, which is crucial given that some systemic psoriasis treatments might reduce the risk of transitioning to PsA.

Psoriatic arthritis definitions

The 10 points highlight that arthralgia, together with abnormalities seen on ultrasound or magnetic resonance imaging scans, represent key elements of subclinical PsA that could serve as short-term predictors. Additionally, the more traditional risk factors for PsA – such as psoriasis severity, obesity and nail involvement – can be seen as more long-term disease predictors.

EULAR suggests standard naming to define the three distinct stages relevant to the prevention of PsA: people with psoriasis at higher risk of PsA, subclinical PsA and clinical PsA. This, the EULAR group felt, was important because in other inflammatory rheumatic musculoskeletal diseases, such as rheumatoid arthritis, the clinical onset is usually preceded by a preclinical phase encompassing arthralgia and immunological or imaging abnormalities, but without a clinical diagnosis.

A definition for early psoriatic arthritis was proposed by EULAR based on the development of joint swelling as a clinical outcome measure for trials of PsA prevention.

EULAR believes that the points to consider will help to define the clinical and imaging features of those with psoriasis that raise the index of suspicion for progression to PsA. Furthermore, these points could be used to identify people who could benefit from a therapeutic intervention to delay or prevent PsA.

An additional and important practice issue, is that clinicians inform patients with psoriasis about the risk of developing PsA and encourage them to report any joint-related symptoms to facilitate early diagnosis. Previous studies have shown that even a diagnostic delay as short as six months can lead to significantly more severe radiographic joint damage, worse physical function and decrease the changes of therapeutic success

Apremilast benefits in psoriatic arthritis revealed by magnetic resonance imaging

15th June 2023

The impact of apremilast on inflammatory and structural changes in psoriatic arthritis (PsA) can be better understood through magnetic resonance imaging (MRI), according to a recent study presented at the European Congress of Rheumatology (EULAR) 2023.

The data came from the MOSAIC phase 4, multicentre, single-arm, open-label study, in which the researchers used MRI to examine the effect of the oral immunomodulating phosphodiesterase-4 inhibitor apremilast on inflammation in patients with active PsA.

MOSAIC was the first trial to use MRI to assess inflammation in peripheral joints and entheses instead of traditional X-ray methods. Participants received oral apremilast 30 mg daily, either as monotherapy or in combination with stable methotrexate. Treatment continued for 48 weeks and individuals had an MRI scan of the hand performed at baseline and at Weeks 24 and 48.

Researchers set the primary endpoint as the change from baseline in the composite score of hand bone marrow oedema, synovitis and tenosynovitis in fingers two to five, assessed by the PsA MRI Score (PsAMRIS) at Week 24, and for which a negative change reflects disease improvements.

In addition, a total inflammation score, which comprised of bone marrow oedema, synovitis, tenosynovitis and periarticular inflammation in fingers, was also assessed. The team also considered disease activity with the clinical disease activity index for psoriatic arthritis (cDAPSA), which is lowered as disease activity reduces.

Apremilast and inflammatory changes

MOSAIC enrolled 122 patients who received apremilast. The mean age was 47 years (55% women) and the mean duration of PsA was 1.9 years. Some 98 patients provided evaluable data for the primary endpoint.

The least-squares mean change from baseline in the composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis assessed by PsAMRIS was -2.32 at Week 24 and -2.91 at Week 48.

Significant improvements from baseline were also seen in total inflammation scores for those taking apremilast, together with a reduction in cDAPSA score. In addition, no significant structural progression was observed.

The researchers suggested their findings highlighted the value of using MRI and PsAMRIS as measures of disease activity change following PsA treatments.

Meet the Expert: Philip Mease on psoriatic arthritis

6th January 2023

Philip Mease is a rheumatologist based in Seattle, Washington, and has been in practice since 1982. He spoke to Hospital Healthcare Europe about the management of psoriatic arthritis and findings from the DISCOVER-2 trial.

Philip Mease has an interest in psoriatic arthritis (PsA), which arose after working alongside a dermatology department in Seattle where he treated many patients referred by dermatologists for the treatment of their arthritic component. His work on PsA took off after undertaking a clinical trial with etanercept in 2000.

Since then, he has continued to play an active role in clinical research on PsA, as well as mentoring clinicians and was involved in the establishment of GRAPPA, a multidisciplinary, non-profit, organisation that promotes and disseminates information on PsA.

Understanding psoriatic arthritis

As Dr Mease explained, ‘psoriatic arthritis is a condition that occurs in people with psoriasis’ and that in the US and Western Europe, psoriasis occurs in around three out of 100 individuals and, of those, ‘one out of the three will have manifestations of PsA.’ He described how PsA is a unique presentation in that any joint in the body can become inflamed. A key feature of PsA Dr Mease added, was how patients can get inflammation where tendons or ligaments insert into bone. For many, the Achilles tendon is affected and this is referred to as enthesitis and which, he says, ‘can be quite disabling for patients, especially low extremity enthesitis.’ A further hallmark presentation, dactylitis, occurs on fingers or toes in which the whole digit swells, becoming sausage-like, reflecting inflammation in both the synovium and bone. Another area of the bone affected in 40-50% of patients he said, was the spine and whilst quite disabling, he finds this is often missed because of the belief that back pain invariably occurs due to degenerative arthritis of the spine as opposed to an immunologic inflammation.

Given the combination of a painful arthritis and an unsightly skin and nail disease, Dr Mease is unsurprised that such patients experience a significant detriment in their quality of life, characterised by a higher incidence of depression and suicidal ideation than for most other chronic disease.

As Dr Mease explained, rheumatoid arthritis tends to be more common in women and is predominately restricted to inflammation of the synovial lining tissue of the joints and without some of the defining features (e.g. enthesis) of PsA. In contrast, PsA is equigender – occurring equally in males and females – and tends to present in fewer joints. He also noted that PsA rarely occurs in the absence of the cutaneous manifestation of psoriasis that sometimes the arthritis precedes the development of skin-related symptoms. On average, he says, ‘people will develop psoriasis about 10 years before they develop the arthritis manifestations.’

Diagnosing PsA

Unfortunately, and unlike rheumatoid arthritis, Dr Mease revealed how there are no specific clinical biomarkers indicative of PsA. Consequently, the diagnosis is a clinical one and rests on the presence of specific symptoms and the presence of concomitant psoriasis.

While there are some biomarkers that are elevated in PsA, none of these are particularly informative. For instance, inflammatory markers such as C-reactive protein are sometimes elevated, but as he says, ‘this only happens in around 40% of the time, even in patients with very active disease.’ Occasionally, he added, a gene marker, HLA b27 is measured when investigating the presence of spinal involvement but again, ‘maybe about 30% of patients with spinal involvement will have the presence of this particular gene marker.’

While disabling, as Dr Mease explained, the symptoms of PsA such as joint pain, stiffness and swelling can vary considerably among sufferers. For some patients, these symptoms can be particularly burdensome, occurring daily, whereas for others, symptoms may persist for several weeks at a time before quiescence. A further complication is PsA is degenerative, resulting in the destruction of bones and joints, leading to constant, debilitating pain.

He believes that PsA can be diagnosed by both dermatologists and rheumatologists although recognises how many dermatologists freely admit to being unable to differentiate between PsA and osteoarthritis or sometimes, might not even enquire about the presence of musculoskeletal symptoms in their psoriasis patients.

Patient burden and prognosis

With a cosmetically disfiguring skin disease and associated painful joints, the burden upon PsA sufferers is huge, severely impacting on social and occupational activities and ultimately their quality-of-life. Dr Mease discussed how in practice patients become overburdened by heightened levels of pain and fatigue together with social embarrassment due to the visible nature of their skin condition.

Although untreated, PsA becomes degenerative over a period of several years, Dr Mease mentioned how in a patient who first presents with dactylitic digit, ‘we can see within a year the destruction of the joint within that finger or toe.’

Although the presence of psoriasis, particularly severe disease, is known to be linked with a higher risk of cardiovascular disease, the association with PsA is less well defined. Nevertheless, as Dr Mease noted, ‘we know that the deeper the inflammatory burden that the patient has, the greater likelihood of associated cardiovascular risk.’ Moreover, given how there is already a genetically predisposed risk for cardiovascular risk in both PsA and psoriasis patients, he sees it as vital to educate both patients and clinicians about this potential higher cardiovascular risk.

The mainstays of treatment

According to Dr Mease, ‘psoriatic arthritis is considered to be an auto-immune disease due to the activation of predominately T lymphocytes but also to some extent, B lymphocyte as well as other immune cells such as natural killer cells.’ Each of these different cells have the capacity to over-produce key pro-inflammatory cytokines including tumour necrosis factor (TNF) and interleukins 17, 23 and, to a lesser extent, interleukin-6. These inflammatory molecules migrate to areas of inflammation and stimulate cells to become overactive. Consequently, these molecules have become a key target for treatment.

While initial management for a psoriasis patient who complains of joint aches and pains might be over-the-counter or prescribed non-steroidal anti-inflammatory agents, by the time they reach a rheumatologist, many will no longer find these drugs to be effective.

While the next step in the UK is the use of immunosuppressants such as methotrexate, Dr Mease described that in the US, recent guidance suggested earlier use of an anti-TNF agent. This he says, is because anti-TNF agents are known to be more effective than immunosuppressants such as methotrexate and help to delay both disease progression and ultimately destruction of joints, making them more cost-effective.

However, Dr Mease depicted how there is a reluctance to use biologics before drugs like methotrexate due to the higher cost of the former agents. Nonetheless, he thinks that this stance may well change in the future after more widespread adoption of biosimilars, which while still expensive, are considerably cheaper than their original reference products and therefore serve to increase patient access to treatment.

The rationale of the DISCOVER-2 trial

Dr Mease described how the overarching aim of the DISCOVER-2 trial was to investigate the ‘safety and efficacy of guselkumab, an IL-23 inhibitor, in treating the various clinical domains of PsA including the ability to inhibit structural damage progression or not.’ The trial itself included over 700 patients with psoriatic arthritis and enabled researchers to document safety and efficacy for the drug and which would form part of the submission required for regulatory approval.

The main efficacy and safety outcomes were assessed after 24 weeks but further assessments were made at 52 and 100 weeks. He stated that an important part of the analysis was the use of non-responder imputation. Using this approach, participants who discontinued therapy for any number of different reasons would be counted as a non-responder.

This was a more stringent test and, as Dr Mease explained, given that ‘three-quarters of the patients had an ACR20 [a composite efficacy measure] response, it was a comment about the efficacy and longevity of the effect of the medication.’

Quick responses

The trial also found how patients responded quickly, with responses seen as early as one month after starting treatment. In addition, Dr Mease described how there was also a climbing response over time, ‘so that an ACR20 response was achieved by about two-thirds of patients at the 24-week mark and by about 50% of patients at the 16-week mark’ and continued to climb as the study continued and were even higher at the 100-week mark.

Dr Mease thinks that the trial showed how treatment with guselkumab not only provides a relatively fast onset of action but also that the response continues to increase over time and probably becomes maximal after 52 weeks. As well as clinical efficacy, Dr Mease described how guselkumab produced a statistically superior response to placebo for all the quality-of-life measures assessed in the trial.

While clearly the response to treatment wanes over time, he noted how biologic registry data, which include thousands of patients, suggests that for this class of drugs, the persistency of response is between 1.5 and 3 years. A further and reassuring point he added was that the emerging registry data tend to mirror the safety profile of agents observed in clinical trials.

Dr Mease also said that there are currently several other drugs being considered for the management of PsA, including interleukin (IL)-17 and -23 inhibitors and TNF inhibitors. Nevertheless, he thinks that IL-23 is a somewhat attractive target for PsA given how blockage of this cytokine is effective against both cutaneous and arthritic symptoms. He mentioned how it was also effective in a subgroup of patients with psoriatic spondylitis in their spine.

Next steps for psoriatic arthritis management

Dr Mease described the emergence of therapies with different molecular targets. One intracellular pathway target is tyrosine kinase 2, which is part of the Janus kinase (JAK) family. The use of an inhibitor of this pathway, deucravacitinib, has been shown to be well tolerated and improves disease severity. In addition, two oral JAK inhibitors, tofacitinib and upadacitinib, have already received FDA approval for PsA. Finally, although not currently available, neurokinin 2 inhibitors are under development for the treatment of not only PsA, but also rheumatoid arthritis and lupus.

Dr Mease believes that the last 25 years has witnessed a significant improvement in both the understanding and treatment of PsA and that today, is what he described as a ‘terrific time to treat people with the condition because we can actually often get them into remission or low disease activity.’

Psoriasis patients self-report higher analgesic usage largely due to joint pain

17th March 2022

Psoriasis patients self-report a greater use of analgesics than the general public largely because of increased joint pain

Psoriasis patients report using more analgesics than members of the general public without the disease and this is largely because of an increased level of joint pain. This was the finding of a study by researchers from the Department of Dermatology and Allergy, Copenhagen University Hospitale-Herlev and Gentofte Hospital, Copenhagen, Denmark.

Psoriasis is best defined as a chronic, immune-mediated inflammatory disease and which varies in prevalence around the world ranging from 30.3 per 100 000 person years to 321.0 per 100 000 person years.

Although psoriasis presents clinically as an inflammatory skin condition, it has become recognised that 1 in 4 patients with psoriasis also have an associated and painful inflammatory joint condition, termed psoriatic arthritis.

While the dry, flaky skin elevated psoriatic plaques are often highly pruritic, over recent years, it has become more apparent that skin pain is a frequently reported and bothersome symptom among people with psoriasis.

Indeed, one retrospective analysis of over 4,500 psoriasis patients clearly showed how patients experience pain, finding that two-thirds were co-prescribed non-steroidal anti-inflammatory drugs, 59.5% other analgesics and 45.9% opioids.

What remains unclear however, is why people with psoriasis take analgesics and so for the present study, the Danish team turned to data contained within the Danish Skin Cohort to assess disease burden and the use of analgesics among psoriasis patients with and without psoriatic arthritis (PsA) and for comparative purposes, included a control group without either condition.

Psoriasis patients and use of analgesics

A total of 3169 patients with psoriasis only and a mean age of 59 years (55.8% female) were included along side, 3490 controls and 847 individuals with both psoriasis and PsA.

The median skin and joint pain in the general population was 0 and 2 respectively. In contrast, moderate-to-severe skin pain was reported by 30% of those with PsA and 21% with psoriasis alone (p < 0.0001). In addition, moderate-to-severe joint pain was reported by 69% of those with PsA and 45% of those with only psoriasis (p < 0.0001).

The use of opioid analgesics in the last 12 months was reported by 9% of the control group, 14.2% of those with psoriasis alone but 22.7% of those with both psoriasis and PsA. Using multivariable regression, the authors calculated that only joint pain was significantly associated with the use of analgesics (odds ratio, OR = 3.72, 95% CI 2.69 – 5.14, p < 0.001).

The authors concluded that physicians should pay increased attention to those with psoriasis who report any joint pain in order to further improve their clinical management.

Citation
Loft N et al. Disease burden, symptoms, and use of analgesics in patients with psoriasis with or without psoriatic arthritis: A cross-sectional study J Am Acad Dermatol 2022

Skyrizi receives MHRA approval for psoriatic arthritis

2nd December 2021

Skyrizi has now received approval from the UK regulator, the MHRA, for use in the treatment of patients with active psoriatic arthritis

Skyrizi (risankizumab) has been approved by the UK regulator, the MHRA, for the use in adults with active psoriatic arthritis. This follows the EMA approval earlier this month.

The Summary of Product Characteristics (SPC) of the drug has been updated to reflect this change, stating that it is indicated either ‘alone or in combination with methotrexate (MTX), is indicated for the treatment of active psoriatic arthritis in adults who have had an inadequate response or who have been intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs).’

Skyrizi is a monoclonal antibody and blocks the action of interleukin 23, (IL-23), which is believed to play an important role in psoriatic arthritis. The approved dose for risankizumab is 150mg, administered by subcutaneous injection at week 0 and 4, and every 12 weeks thereafter.

The approval was based on data from two clinical studies, KEEPsAKE-1 and KEEPsAKE-2 and although both of the trials included patients with moderate to severe PsA, the populations were slightly different. For example, KEEPsAKE-1 included patients who had with an inadequate respond to one or more DMARDs whereas KEEPsAKE-2 recruited those with an inadequate response to other biologicals. However, both studies had the same primary endpoint of an ACR20 response at week 24. In addition, secondary outcomes included improvements in several clinical manifestations of psoriatic arthritis such as physical functioning (as assessed by the Health Assessment Questionnaire Disability Index [HAQ-DI]) and minimal disease activity (MDA) and both the primary and secondary endpoints were assessed after 24 weeks of therapy.

In KEEPsAKE-1 57.3% of patients receiving risankizumab achieved the primary endpoint at week 24 compared to 33.5% in the placebo group (p < 0.001). Similarly, in KEEPsAKE 2, 51.3% achieved the primary endpoint compared with 26.5% in the placebo arm (P< 0.001).

There were also significantly greater improvements in the secondary outcomes for risankizumab-treated patients. For example, in KEEPsAKE-1, there was a -0.31 change in HAQ-DI compared to -0.11 (placebo) and in KEEPsAKE 2, a change of -0.22, compared to -0.05 in the placebo group (for both differences, p <0.001).

Risankizumab approved by EMA for active psoriatic arthritis

22nd November 2021

Risankizumab can now be used by patients with active psoriatic arthritis after an inadequate response or intolerance to one or more DMARDs

The European Medicines Agency (EMA) has approved the use of risankizumab (brand name Skyrizi) for the treatment of patients with active psoriatic arthritis (PsA) who have failed to adequately response to one or more disease modifying anti-rheumatic drugs (DMARDs) or who are intolerant to DMARDs.

Psoriatic arthritis is an inflammatory arthritis affecting the joints and connective tissue which is associated with psoriasis and which is present on the skin or nails. While the prevalence of psoriasis in the general population is low, at around 3%, at least 20% of psoriasis patients have PsA which is a progressive disease that ranges from mild synovitis to severe erosive arthropathy. Sufferers of PsA experience joint inflammation which causes swelling and pain and which has a negative impact on their quality of life.

The treatment of PsA starts with non-steroidal anti-inflammatories and as the disease progresses, escalates to oral corticosteroids, DMARDs and finally biologic agents. There are currently several biologics approved for the management of PsA including ixekizumab and guselkumab. Skyrizi was previously approved by the EMA in 2019 for the treatment of plaque psoriasis but that has been extended to include PsA.

Clinical efficacy

The EMA approval of Skyrizi (risankizumab) was based the findings of two Phase III clinical trials, KEEPsAKE-1 and KEEPsAKE-2. Both trials were placebo-controlled trials in patients with moderate to severe PsA although KEEPsAKE-1 included patients with an inadequate respond to one or more DMARDs whereas KEEPsAKE-2 recruited those with an inadequate response to other biologicals. In both trials patients received skyrizi at subcutaneous dose of 150 mg and the primary outcome for both studies was the ‘percentage of Participants Achieving at least 20% Improvement in American College of Rheumatology (ACR20)‘.

The ACR20 is a composite measure defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).

In both trials, the ACR20 response was set as the primary endpoint and assessed after 24 weeks. Secondary endpoints included the Health assessment questionnaire disability index (HAD-DI), which represents a measure of physical function and the proportion of patients achieving minimal disease activity (MDA).

In KEEPsAKE-1 (KS1) and KEEPsAKE-2 (KS2), 57.3% and 51.3% of patients respectively, given risankizumab achieved the primary endpoint compared to 33.5% and 26.5% receiving placebo (p<0.001).

Similarly, improvements in HAQ-DI of -0.31 (KSI) and -0.22 (KS2) compared with -0.11 and -0.05, in the respective placebo groups was seen at week 24 (p<0.001). Finally, 25% (KS1) and 25.6% (KS2) of Skyrizi patients achieved MDA, compared to 10.2% (KS1) and 11.4% (KS2) of those on placebo (p<0.001).

In terms of safety, serious adverse events occurred in 2.5% (KS1) and 4% (KS2) of patients given Skyrizi although this was comparable to the placebo rate (3.7% and 5.5%, KSI and KS2).

According to the EMA approval, Skyrizi can be used either alone or in combination with methotrexate.

Source. Abbvie press release. 17th November 2021

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