Psoriasis and Psoriatic Arthritis: Harnessing the Potential of Targeted Therapies
Psoriasis and Psoriatic Arthritis-Harnessing the Potential of Targeted Therapies
The psoriasis and psoriatic arthritis (PsA) treatment paradigm has changed dramatically over the past decade, largely due to the availability of novel biologics that better control the signs and symptoms of these diseases. Ever since the Food and Drug Administration (FDA) granted marketing authorization for Enbrel® (etanercept) for the treatment of PsA in 2002, the market has become increasingly competitive as more biologics for both psoriasis and PsA come to market. The case is the same in Europe, with the European Medicines Agency (EMA) generally following the United States (US) approval sequence, with a few months difference.
Key: EMA = European Medicines Agency, PsA = psoriatic arthritis
While regulatory approval has moved quickly, the recent biologic market entrants have experienced challenges in securing access and reimbursement in some countries. And of those newer agents that received a positive decision, several are subject to a patient access scheme (PAS) or restricted by criteria that limit their use to more severe patient populations or specific patient subgroups. To examine these patterns in more detail, the health technology assessment (HTA) decisions made by the National Institute for Health and Care Excellence (NICE) in the United Kingdom (UK) and the Haute Autorité de Santé (HAS) in France were summarized by drug class. The HTA decisions by the Germeinsamer Bundesausschuss (G-BA) in Germany were also considered, along with the upcoming treatments that may be undergoing review in the near future.
Tumor Necrosis Factor (TNF) Inhibitors
Two main principles have been used by NICE and HAS to manage reimbursement criteria and eligible patient populations: the disease severity and place of therapy in the disease management continuum. The HTA bodies also generally recommend that biologics be discontinued in people whose psoriasis has not responded adequately after induction treatment.
The efficacy of TNF inhibitors in patients with PsA has been established in many studies, and they are an integral part of the treatment recommendations for PsA. Etanercept, infliximab, adalimumab, and golimumab have been recommended by NICE in the UK for the treatment of adults with active and progressive PsA. Golimumab is the only TNF inhibitor subject to a PAS, whereby the 100 mg dose is made available to the National Health Service at the same cost as the 50 mg dose. In Germany, all anti-TNFs are available within their licensed indications. In France, HAS determined that the 3 “original” anti-TNFs (etanercept, infliximab, and adalimumab) yield a substantial actual benefit (ie, Service Médical Rendu [SMR]) and substantial improvement in actual benefit (Amélioration du Service Médical Rendu [ASMR] II) over methotrexate in adult patients with active, progressive PsA who are responding inadequately to disease-modifying antirheumatic drugs (DMARDs).
One can see how the increased number of treatment options has made it more difficult for later market entrants to garner a favorable rating. Golimumab, which was assessed 5 years after the “original” anti-TNFs, was deemed by HAS to provide a substantial actual benefit in PsA, but to provide no improvement in the actual benefit (ASMR V) over other TNF inhibitors. Close to 3 years later, certolizumab yielded only a moderate benefit and no improvement in the actual benefit (ASMR V) over other TNF inhibitors. This class of medications is undergoing further expansion with recent approvals of infliximab and etanercept biosimilars for PsA and psoriasis, along with the development of other anti-TNF biosimilars. The reimbursement landscape continues to evolve in terms of how it relates to these new market entrants, and some countries, such as France, compare new entrants to the full list of treatment options available for psoriasis and PsA.
Ustekinumab was the first anti-IL-12/23 agent approved in the European Union (EU) for psoriasis in January 2009, and it was approved for PsA 4 years later. Two anti-IL-17 treatments were also recently approved by the EMA for the treatment of moderate to severe plaque psoriasis: secukinumab in January 2015, and ixekizumab in April 2016. In addition to ustekinumab, secukinumab is the only other anti-IL agent for PsA. On the horizon, brodalumab and tildrakizumab are novel anti-ILs currently in development for psoriasis.
Ustekinumab and secukinumab have received positive NICE recommendations for use in severe psoriasis that has not responded, is intolerant, or has contraindication to standard systemic therapies. In both cases, a PAS was agreed to with the Department of Health, with the manufacturer of ustekinumab agreeing to provide the 90 mg dose at the same cost as the 45 mg dose, and the manufacturer of secukinumab agreeing to provide a simple discount. Ixekizumab is still in the midst of the NICE appraisal process and a decision is anticipated in April 2017. In France, positive assessments highlighting a minor improvement in the actual benefit (ASMR IV) were also obtained from the HAS for both products. These products are also available in Germany within their licensed indications, and ustekinumab was even listed as an appropriate comparator (alongside the “original” anti-TNFs) for future psoriasis indications during the secukinumab G-BA assessment.
For PsA, ustekinumab was recommended by NICE in the UK in adults when treatment with TNF-α inhibitors is contraindicated, or in individuals who have had treatment with 1 or more anti-TNFs. A NICE appraisal for secukinumab in PsA is currently in progress and is expected to be published in February 2017. HAS determined that both ustekinumab and secukinumab did not provide any improvement in the actual benefit (ASMR V) compared with anti-TNFα agents in the treatment of active PsA in adults when response to previous non-biological DMARD therapy has been inadequate.
Phosphodiesterase-4 (PDE4) Inhibitors
Occupying a class all by itself, apremilast is the only EMA-approved PDE4 inhibitor indicated for psoriasis and PsA (approved in January 2015). Apremilast has been assessed by HTA bodies following its EMA approval, but has had challenges differentiating itself in terms of its added benefit compared with existing biologics in both indications. Unfavorable recommendations were rendered by NICE in the UK, as well as by Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) in Germany. France, on the other hand, was mixed in its assessment of apremilast: the product was determined to have no actual benefit as monotherapy in PsA, but it was considered to have at least a moderate to low benefit in combination with other therapies for psoriasis and PsA.
Over the last 15 years, the arrival of biologic therapies has significantly transformed the approach to managing psoriasis and PsA. The landscape continues to evolve today as more biosimilars emerge and as assessments are ongoing in the child and adolescent populations. Furthermore, other mechanisms of action (such as janus kinase [JAK] inhibitors and adenosine A3 receptor antagonists) are being investigated for psoriasis and PsA, and may have a major impact on future HTA decisions and treatment pathways.
Because the original biologics have a firm hold as the primary treatment option for psoriasis and PsA, any novel therapies primed to enter the market must be prepared to compete against established therapies and fend off biosimilars. PASs and rebates have been one key strategy used to improve the cost-effectiveness of certain biologics and secure market access in the EU, enforcing the need for country-specific value and evidence generation to avoid price erosion. The ever-changing psoriasis and PsA landscape reaffirms that manufacturers must be very familiar with each country’s evidentiary requirements to gain access and reimbursement for novel therapies.
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