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New GRAPPA recommendations for the management of psoriasis and psoriatic arthritis: process, challenges and implementation

In 2015, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) presented updated recommendations on the management of psoriasis and psoriatic arthritis (PsA). This updated earlier recommendations to keep pace with the significant progress in PsA research. This editorial summarizes the methodology in their development and assesses their practicalities of application in clinical practice in both dermatology and rheumatology. GRAPPA is a global research group dedicated to both psoriasis and PsA (http://www.grappanetwork.org). These recommendations therefore cover treatment of both dermatological and musculoskeletal manifestations. The recommendations were led overall by a small steering committee, but appraisal of the evidence and initial generation of treatment recommendations were carried out in domain subcommittees with expertise in that particular area of psoriasis or PsA. Rheumatologists chaired the groups looking at musculoskeletal manifestation (peripheral joints, axial disease, enthesitis and dactylitis), while dermatologists chaired groups focused on skin and nail disease in the setting of PsA. A new group was also convened to address comorbidities in PsA, including both extra-articular spondyloarthritis manifestations and distinct comorbidities such as cardiovascular disease, metabolic syndrome, depression and skin cancer. Patient research partners were included in the groups to ensure a full patient perspective. Following on from the initial development, the GRAPPA patient research partners are now writing a lay summary of the recommendations specifically for dissemination to patients. The recommendations are based on a large systematic literature review to provide the evidence base. In this latest set of recommendations, GRAPPA elected to use Grading of Recommendations Assessment, Development and Evaluation (GRADE) in the latest update to assess the evidence (http://www.gradeworkinggroup.org/). GRADE gives strong or conditional recommendations following assessment of desirable and undesirable consequences, quality of evidence, values and preferences and resource use. This is now recommended by a number of organizations including the World Health Organization. After some debate, data from conference abstracts were included in this review even if the full paper had not been published. Recommendations based on high-quality abstract data are included to prevent rapid outdating of the recommendations, but these are ‘conditional’ and are clearly demarcated as such in the treatment schema. Face-to-face meetings of the subcommittees and GRAPPA full-membership meetings took place to allow all active members a voice in the discussion. Drafts of the overarching principles, evidence table and treatment schema were disseminated to all GRAPPA members, including patient research partners, to allow feedback from all members before 145 participants voted on agreement. The principal outputs of the GRAPPA recommendations are a summary table of the evidence base for therapies in different domains of psoriatic disease, a table highlighting issues with individual therapies in key comorbidities and a summary treatment schema that includes six individual algorithms for the domains of disease, which can be used to guide therapeutic decisions (Fig. 1). The major differences between the current GRAPPA recommendations and those drawn up by GRAPPA in 2006 are the abandonment of the severity grading (as this was thought not to be evidencebased), the inclusion of algorithms for each domain, the separation of the cutaneous domain into skin and nails and the addition of a section on comorbidities. In the U.K., the treatment of patients with psoriasis and PsA is directed largely by the National Institute for Health and Care Excellence (NICE) guidelines. The new GRAPPA recommendations update this, as they include ustekinumab, secukinumab and phosphodiesterase (PDE)4 inhibitors. They also include drugs not currently licensed for treating psoriasis in the U.K., such as the fumaric acid esters. Despite the lack of trial evidence for methotrexate, this drug is still the first disease-modifying antirheumatic drug (DMARD) to which rheumatologists turn. Its efficacy on skin is undoubted, and observational studies support its use in the joints. However, toxicity remains a problem, and the other conventional DMARDs have equally poor evidence for efficacy. Leflunomide is helpful for the joints, but not the skin, and the opposite is true for ciclosporin; both have toxicity issues. From a rheumatology perspective, updating the treatment recommendations is important for several reasons. There have been new developments in pathophysiology, disease assessment and targeted therapies, and increasing recognition of comorbidities. The new disease-specific therapies target the interleukin (IL)-12/23 axis, with IL-17 ‘downstream’ of IL23. In addition, a new targeted synthetic drug, blocking PDE4, has become available. These emerging therapies have been incorporated into the new schema, but often with a provisional rating, reflecting the fact that the evidence is as yet not fully published. Where these new therapies fit into our current treatment algorithms is as yet undefined.