Comorbidities associated with PsA include uveitis, inflammatory bowel disease, obesity, metabolic disease (diabetes, hypertension, hyperlipidaemia, fatty liver disease, cardiovascular diseases), depression, and anxiety. It is important to keep these comorbidities in mind when selecting therapy.⁶ 

Musculoskeletal manifestations of PsA include peripheral arthritis, spondylitis, dactylitis (inflammation of the whole digit), and enthesitis (inflammation where a tendon, ligament, or joint capsule inserts onto the bone). Apart from psoriasis, other skin manifestations associated with PsA include nail disease.⁶  

Impact on QoL 

Nearly 40% of patients living with PsA report that the disease has a profound effect on their daily lives. Beyond the musculoskeletal and skin effects, patients living with PsA experience fatigue as well as diminished work capacity, and social participation. Patients report struggling with low self-esteem, feeling physically unattractive or sexually undesirable, embarrassed, helpless, and depressed.^6,7  

In terms of physical limitations, an estimated 47% of patients develop joint damage within two years of disease onset, which impacts their mobility and may result in decreased sleep and energy, and difficulties with activities of daily living, including climbing stairs, bathing, dressing, working, and exercising.⁷ 

Which patients living with psoriasis are at risk of PsA? 

The onset of PsA usually occurs in the 30s and 40s age groups. The disease affects men and women equally. In the majority of patients (68%), psoriasis precedes the onset of PsA. In about 15% of patients, arthritis coincides with psoriasis, and in 17% of patients, arthritis occurs before the onset of psoriasis.⁸ 

Studies show that patients:^7,8  

• With severe psoriasis are at increased risk of PsA. A longitudinal, retrospective, population-based cohort study of psoriasis report that having more than three body sites affected by the disease (compared with only one site) is associated with a 2.24-fold increased risk of PsA 
• With a positive family history of psoriasis have an increased risk of PsA. Between 33% to 50% of patients living with PsA have at least one first-degree relative who has psoriasis or PsA 
• Exposed to environmental triggers such as infection or mechanical stress, which initiates a chronic inflammatory process primarily involving the joints and skin, resulting in the production of interleukin (IL)-23, are at increased risk of psoriasis and PsA 
• Those Who have scalp lesions have a 3.89-fold and those with intergluteal or perianal lesions have a 2.35-fold increased risk of PsA 
• Those Who have psoriatic nail involvement are at increased risk. 

How is PsA diagnosed? 

There are currently no diagnostic tests or criteria available to diagnose PsA. Therefore, diagnosis is based on inflammatory musculoskeletal features in joints, entheses of the spine, skin, and/or nail psoriasis.¹  

To aid clinicians, the minimal disease activity (MDA) criteria (see box 1) were developed. The MDA criteria have been shown to have prognostic value in terms of quality of life, radiographic damage, and work stability, and correspond highly with a level of symptoms.⁵  

Tight control improves patient outcomes 

Using the MDA criteria, Coates et al (2015) conducted the first study to demonstrate improved clinical and patient-reported outcomes, with a ‘treat to target’ approach.^5,9  

The primary outcome of the Effect of tight control of inflammation in early PsA (TICOPA) trial, was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 48.⁹  

The odds of achieving ACR20 (odds ratio [OR] 1.91), as well as ACR50, ACR70, and psoriasis area and severity index 75, were significantly higher in the tight control group. Improvements in patient-reported outcomes, such as physical function (measured by the Health Assessment Questionnaire) and quality of life (measured by the PsA quality of life, were seen with tight control.^5,9 

Based on the results of the TICOPA trial, the European Alliance of Associations for Rheumatology (EAAR) – formerly known as the European League Against Rheumatism – incorporated the treat-to-target concept in their 2015 guidelines. The authors recommended that ‘treatment should be aimed at reaching the target of remission or minimal/low disease activity, by regular monitoring and appropriate adjustment of therapy’.¹¹ 

When to step-up treatment 

According to the 2021 guidelines developed by the Group for the Research and Assessment of Psoriasis and PsA (GRAPPA), the ultimate goals of therapy for all patients living with PsA are to:¹¹ 

• Achieve the lowest possible level of disease activity in all domains of disease
• Optimise functional status, improve quality of life and well-being, and prevent structural damage to the greatest extent possible
• Avoid or minimise complications, both from untreated active disease and from therapy.

The GRAPPA authors stress that therapeutic decisions need to be individualised and are made jointly by patients and their clinicians. Treatment should reflect patient preferences, with patients being provided with the best information concerning relevant options.¹¹  

Furthermore, the GRAPPA guideline states that treatment choices may be affected by various factors, including disease activity, previous therapies, prognostic factors such as structural damage, comorbid conditions, cost, and convenience.¹¹  

GRAPPA and EAAR recommend a standard ‘step-up’ approach, although both allow for ‘skipping ahead’ based on the severity of the disease or the presence of specific disease features such as enthesitis.^11,12,13  

The GRAPPA recommendations suggest wherever possible, treatment for an individual should be selected to address all active domains (eg peripheral arthritis, axial disease, enthesitis, dactylitis, and skin and nail psoriasis) of the disease and any related conditions. The presence of poor prognostic signs should accelerate treatment, noted the authors.⁶  

The EAAR also recommends that patients with poor prognostic factors should be treated more aggressively. Indications for stepping-up treatment include many swollen joints, structure damage in the presence of inflammation, high sedimentation rate or c-reactive protein, and/or clinically relevant extra-articular manifestations.⁶ 

Treatment recommendations 

GRAPPA recommends starting with topical therapies for psoriasis and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for treatment naïve patients with predominantly peripheral arthritis. Expedited treatment routes, which include the use of biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs), can be used as first-line therapy if available.^11,13 

The latest EAAR guidelines (2019), recommend non-steroidal anti-inflammatory drugs (NSAIDs) and local glucocorticoid injections as initial therapy. Rapid initiation of csDMARDs is recommended for patients with poor prognostic factors such as polyarthritis or monoarthritis/oligoarthritis accompanied by factors such as dactylitis or joint damage. The EAAR recommends methotrexate as the first csDMARD unless there are contraindications.^12,13  

If the treatment target is not achieved with this strategy, bDMARDs targeting tumour necrosis factor (TNF), IL-17A, or IL-12/23 should be initiated, taking skin involvement into account.¹²  

If axial disease predominates, a TNF inhibitor or IL-17A inhibitor should be started as first-line DMARD. The use of Janus kinase inhibitors is recommended after bDMARD failure.¹²  

The 2019 ACR/National Psoriasis Foundation (NPF) guidelines recommend a TNF inhibitor as first-line therapy and not an oral drug such as methotrexate for patients with active peripheral PsA.¹³    

The authors did point out that this recommendation is conditional and has several caveats. For example, if the patient prefers an oral drug, has mild disease, or has contraindications to a TNF inhibitor, the patient would start an oral drug first.¹³  

In both the EAAR and GRAPPA guidelines, TNF inhibitors are recommended as first-line after csDMARDs. Furthermore, GRAPPA includes IL-12/23 inhibitors and IL-17 inhibitors as first-line options after csDMARDs.^11,12,13   

Conclusion  

Although the guidelines differ in terms of treatment recommendations, all three support a treat-to-target approach. The 2015 TICOPA trial was the first to demonstrate the value of a treat-to-target in PsA. Since then, several studies have confirmed that a treat-to-target approach to PsA management, aiming for remission or low disease activity, results in better clinical, radiographic, and patient-reported outcomes ^9,13,14  

REFERENCES 

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3. Hackett S, Ogdie A, Coates LC. Psoriatic arthritis: prospects for the future. Ther Adv Musculoskelet Dis, 2022.
4. Tarannum S, Leung YY, Johnson SR, et al. Sex- and gender-related differences in psoriatic arthritis. Nat Rev Rheumatol, 2022.
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