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A Domain-Based Approach to the GRAPPA Psoriatic Arthritis Treatment Recommendations

With their publication in June 2022 (1), the 3rd iteration of the Group for Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Treatment recommendations for Psoriatic Arthritis (PsA) may have set a record or sorts.

Spurred by the tremendous progress and innovation in the field, it was clear that the previous 2015 guidelines needed revision; the earliest work began initially in 2018. Due largely to the impacts of the COVID pandemic, the gestation period was prolonged until recently, almost 4 years later. According to the Guinness book of world records, the common frilled shark, (Chlamydoselachus anguineus),an extremelyprimitive species native to all oceans of the world, has the longest recorded gestation period of any animal species, at 3.5 years!           

Recently, GRAPPA published updated treatment recommendations for PsA in Nature Reviews Rheumatology.The GRAPPA recommendations join a large and diverse assortment of treatment recommendations or guidelines for PsA, including those from the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF), those produced by the European Alliance of Associations for Rheumatology (EULAR), and many from individual countries. While some of these are relevant across jurisdictions, the GRAPPA recommendations were designed from the start to be international in scope with applicability across very diverse healthcare systems.

Key differentiators of the GRAPPA recommendations are that they follow a domain-based approach considering 6 key domains of psoriatic arthritis (peripheral arthritis, axial arthritis, skin psoriasis, nail psoriasis, enthesitis, dactylitis; and also related conditions – see below). Unlike a number of rheumatology or dermatology society recommendations, the GRAPPA recommendations were designed to broadly cover and focus on the management of both musculoskeletal and skin disease. Thus, evidence for drug efficacy was extracted from the relevant literature and considered separately for all the domains of disease, as each can be of importance to individual patients.

Recommendations for PsA have become increasingly important as clinicians grapple with expanding treatment options in the field.  Increasing access to drugs with novel modes of action is welcome, but an increased choice leads to challenges in selecting the most appropriate therapy for each individual patient.  The need for a domain-based approach is underpinned by the differential efficacy of targeted therapies in the different domains of disease. Most of the large randomized controlled trials in PsA have shown similar effects of various treatments on peripheral arthritis. To date, head-to-head trials in PsA are limited and only available for TNFi vs IL-17A and TNFi vs JAKi. In those trials, while similar ACR20 responses have been seen clear differences in response have been elucidated in other domains.

With current data, this seems particularly important in the domains of axial disease and skin disease.  There are limited studies in axial PsA, so treatment usually follows evidence from wider axSpA studies.  Here, a number of drugs that are effective in peripheral psoriatic arthritis have been shown to be ineffective in ankylosing spondylitis trials including multiple conventional DMARDs, IL12/23i, apremilast and IL-23i.  Thus, the presence of axial disease in an individual patient in clinic will have a profound effect on treatment selection.

The other key domain with differential efficacy is psoriasis. In the head-to-head PsA trials, differences were shown in psoriasis outcomes with superior PASI outcomes with IL-17i compared to TNFi.  Further studies in pure psoriasis populations also provide head-to-head comparisons for a wider variety of treatments and have demonstrated that novel therapies, such as IL23i have superior outcomes in skin disease.

Another key change to the 2021 GRAPPA Recommendations is the inclusion of uveitis and inflammatory bowel disease (IBD) in the main treatment algorithm.  Previously, these were considered in the GRAPPA recommendations within the comorbidities group. However, in this update, we separated related conditions into their own category.  We did this to recognise the pathological link between PsA, IBD and uveitis, but also because of the strong overlap between treatment of these conditions.  Whilst the GRAPPA recommendations don’t provide recommendations on all drugs used to manage these conditions, they do provide insight on the suitability of all medications that ‘overlap’ between PsA and uveitis/IBD.

The most recent GRAPPA treatment recommendations reflect the work of a very large and diverse group of individuals over many However, months.  Myriad discussions were held within domain groups and overall, with the attempt to make these the most useful recommendations possible.  In addition to the main publication, in order to review details of the literature searches and analyses and deliberations, there will be separate publications from each of the 8 groups highlighting this work.

(1).  Coates LC, Soriano E, Corp N, Bertheussen H, Callis Duffin K, Campanholo CB, Chau J, Eder L, Fernandez-Avila D, FitzGerald O, Garg A, Gladman DD, Goel N, Helliwell PS, Husni ME, Jadon DR, Katz A, Laheru D, Latella J, Leung Y-Y, Lindsay C, Lubrano E, Mazzuoccolo LD, Mease PJ, O’Sullivan D, Ogdie A, Olsder W, Palominos PE, Schick L, Steinkoenig I, de Wit M, van der Windt DA, Kavanaugh A.  Group for research and assement of psoriasis and psoriatic arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021 Nat Rev Rheumatol. .



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