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Toss of a Coin - How do You Choose PsA Medication?

Psoriatic disease is a multisystem condition with primarily skin and joint manifestations. In addition to the psoriasis phenotype (e.g., plaque, inverse, pustular, guttate, and erythrodermic), there are various phenotypes of psoriatic arthritis including peripheral, axial, mutilans, and oligoarthritis that contribute to the complexity of the disease. Significant comorbidities, or related conditions, such as depression, cardiovascular diseases, inflammatory bowel disease common to psoriatic disease can further modify treatment decisions.

When balancing all these disease domains, individual phenotypes, and comorbidities, sometimes treatment decisions can feel like tossing a coin. Fortunately, numerous guidelines have been published to help us do better than tossing a coin…or do they? 

The management options for psoriatic disease have proliferated in the past few years with many new targeted biologic agents and the issues with cost and access to treatments have added to it complexity of psoriatic arthritis treatment. The most common evidence-based treatment guidelines or recommendations in psoriatic arthritis include ACR/NPF (National Psoriasis Foundation) treatment guidelines (US focused), GRAPPA (global focused) recommendations, and EULAR (European focus) recommendations.  

There are some fundamental differences in treatment guideline development that would be helpful to review. First, the terminology of titles and drug classes of these treatment approaches can vary. The ACR/NPF favors the term “guidelines” and GRAPPA and EULAR favor “recommendations”. The term “guidelines” may feel more fixed as ACR/NPF list more definitive suggestions for treatment scenarios while “recommendations” may feel more unrestricted as it leaves some latitude to the physician and patient decisions.  

In addition to these differences in titles, there were also differences in treatment terms. For example, the oral therapies available for PsA were renamed to OSM (or oral small molecules) in the ACR/NPF while the GRAPPA and EULAR recommendations used the current terminology of csDMARDs (conventional synthetic DMARDs). Second, the methodologies used to develop these also yielded differences in the final treatment selection.  

The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) is a popular one and used by the ACR/NPF and a modified GRADE is used by GRAPPA. This GRADE method uses specific questions named PICO (patient intervention comparator outcome) questions which sets the stage for how the literature review will provide the information to answer these PICO questions and ultimately after a voting process led to treatment decisions. The EULAR recommendations use OCEMB (Oxford Centre for Evidence Based Medicine) methodology. Nonetheless, all guidelines and recommendations aim to create a fair and comprehensive process through a systemic literature review, voting, and consensus to determine the best treatment based on the best evidence for our patients with psoriatic arthritis at the time of publication.

Interesting Differences and Similarities

Among the main differences were the use of DISEASE DOMAINs in the GRAPPA recommendations which included the aformentioned specific PsA phenotypes of peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail disease individually.  The anticipated 2022 GRAPPA recommendations updated from the 2015 publication will be published soon and kept the domain strategy along with comorbidities but also added a new “related conditions” group.  The related conditions group highlighting the nuances of PsA treatment in patients with inflammatory bowel disease and uveitis which are well known conditions that can occur concurrently in our PsA patients. 

The EULAR and ACR/NPF focused on the musculoskeletal domains of PsA and dermatologic domains were not as specific as in the GRAPPA that listed skin and nails individually. The EULAR recommendations report on the musculoskeletal aspects of the psoriatic arthritis patient along with markers of disease severity while ACR/NPF focuses on the active PsA patient who is both treatment naïve and those who continue to have active disease despite initial treatment. Only ACR/NPF addressed the non-pharmacologic therapies while EULAR and GRAPPA do not. However, EULAR has published in the area of CV disease risk in immune mediated diseases, including psoriatic arthritis.

The similarities of the 3 treatment manuscripts include the use of a treat to target approach and the target can be selected by the health care professional involved with the PsA patient. Another interesting similarity is the strong support of having patients involved with the guideline processes (shared decision making). And equally important is that all three treatment guidelines suffer from the lack of data in PsA and reason that many recommendations are conditional rather than strongly recommended.

Treatment Selection

The ACR/NPF presented the most detailed disease definition of “active PsA” in which the guideline would concentrate their treatment guidelines, while the GRAPPA and EULAR disease definition would vary depending on the presence of poor prognostic factors or in the case of GRAPPA, an active disease domain.  

This philosophy led to some differences in the treatment conclusions. One of the main treatment conclusions for the ACR/NPF was the use of TNF monotherapy as first line compared to OSM or combination therapy. This was a conditional recommendation, as patient preference or absence of active disease manifestations, could still result in starting with an oral small molecule. Nonetheless, the ACR/NPF did state in active PsA disease TNFi monotherapy was preferred (based on all data published to date and limited direct comparative data).  

This was in contrast to the GRAPPA and EULAR guidelines which support the use of csDMARDs are first choice with EULAR having a more specific recommendation of the csDMARD as methotrexate first line.  EULAR does highlight the weakness of available methotrexate research data at the time of publication.  In addition, the GRAPPA recommendations do offer a caveat that certain situations with poor prognostic features could endorse the use of a biologic first line over cs DMARDs. 

After failing a 1st line treatment selection, the treatment algorithms differ. In the GRAPPA and EULAR recommendations, the options after csDMARDs include TNFi therapy. In the ACR/NPF, there is support to switch to another TNFi after an initial TNFi failure and prior to switching to a different class of therapeutics. In addition, in the ACR/NPF discussed additional scenarios that include IL-17i over IL-12/23i. In the GRAPPA and EULAR recommendations, it takes on a broader approach after TNFi failures and incorporates many available biologic therapies such as IL-17i, IL-12/23i, and IL-17i into the treatment paradigm. There are also more nuanced recommendation; for example, with patients with axial disease and insufficient response to NSAIDs, therapy with a biologic DMARD should be considered; or patients with predominant enthesitis where TNFi should be considered as first line therapy.

Conclusion

Physicians need to pick an optimal therapy not only based on these available treatment guidelines but also using shared decision making with their patients. We are likely closer to the beginning than the end of the evolving treatment algorithms for PsA.  As soon as these guidelines have been updated, new therapeutic agents are being approved in PsA, adding to the complexity of making up to date treatment selections. 

Advancing imaging techniques and the potential of prognostic biomarkers may also allow us to identify these patients sooner when treatments are likely to work more efficiently.  It is clear that these published treatment guidelines are the result of a herculean effort that includes relevant stakeholders, comprehensive literature searches, and top-notch methodologists. Guidance on these treatment options reflects the available scientific evidence and expert consensus to derive the strength of recommendations match individual patient scenarios. As this has dynamically evolved we we still find ourselves reading and debating these treatment guidelines and recommendations over and over (despite >90% of them are conditional).  

As no two PsA patients are alike, our best efforts need to embrace the art of medicine and rely on the science of medicine in the care of our patients. I still prefer the wisdom afforded by these treatment guidelines and recommendations than not.

References

Singh JA, et al.  Special Article: 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis. Arthritis Rheumatol. 2019 Jan;71(1):5-32. doi: 10.1002/art.40726. Epub 2018 Nov 30. PMID: 30499246; PMCID: PMC8218333.

Coates LC, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 Treatment Recommendations for Psoriatic Arthritis. Arthritis Rheumatol. 2016 May;68(5):1060-71. doi: 10.1002/art.39573. Epub 2016 Mar 23. PMID: 26749174.

Gossec L,  et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 updateAnnals of the Rheumatic Diseases 2016;75:499-510.

 

Disclosures
The author has received compensation as an advisor or consultant on this subject

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