Psoriatic arthritis (PsA) is a chronic inflammatory condition with an estimated prevalence of 64 per 100,000 adults in North America. Whereas 60%-80% of patients with PsA have preexisting psoriasis, 15%-20% develop PsA before psoriasis onset. In terms of age, PsA usually develops in when patients are in their 30s or 40s. Although PsA affects men and women equally, women have higher burden of disease than men. PsA is heterogeneous in presentation, with various manifestations including peripheral arthritis, dactylitis, axial inflammation, enthesitis, and progressive joint damage.
Patients with PsA often present with or later develop comorbid medical conditions. These comorbidities may result from reduced physical function, shared risk factors, and chronic systemic inflammation associated with PsA and its treatment. Common comorbidities associated with PsA include cardiovascular disease (CVD), obesity, metabolic syndrome, liver disease, diabetes, hepatitis B or C infection, and mental health disorders such as anxiety and depression. Comorbidities can adversely affect patients’ quality of life, life expectancy (eg, CVD), and treatment choices.
Although there is no cure for PsA, several medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), biologic and conventional disease-modifying antirheumatic drugs (DMARDs), oral Janus kinase (JAK) inhibitors, and corticosteroid injections are available to help control inflammation, slow disease progression, and relieve pain. However, some of these medications can have a negative effect on comorbidities, leading to adverse events and affecting quality and length of life. Therefore, clinicians must consider the presence of coexisting conditions to determine the optimal and safest treatment strategy.
Treatment Considerations Based on Comorbidity
Patients with PsA have a higher risk of developing CVD. Some studies have found an association between severe and prolonged PsA disease activity and increased CV risk. The use of NSAIDs in patients with PsA and established CVD is therefore challenging due to the risk of CV events associated with NSAID use. However, methotrexate and tumor necrosis factor (TNF) inhibitors can improve endothelial dysfunction, intima-media thickness, and arterial stiffness and may be an appropriate treatment choice for patients with PsA and CVD. There is also evidence that TNF inhibitors may reduce the risk for myocardial infarction; however, more research is needed to confirm this effect.
In addition to CVD, the prevalence of metabolic syndrome and obesity is increased in patients with PsA. Patients with PsA and obesity often have poorer responses to certain treatments, especially TNF inhibitors, compared with nonobese patients. Weight loss, however, has been associated with improved treatment response rates. Methotrexate may be preferable in patients with PsA and metabolic syndrome because it does not seem to increase glycemic levels. Although JAK inhibitors are approved for patients with moderate to severe PsA who have not responded to other treatments, their use is associated with increased lipid levels and CV risk and should be used with caution in patients with PsA and comorbid CV conditions.
Patients with PsA are at an increased risk for metabolic dysfunction–associated steatotic liver disease (MASLD), especially nonalcoholic steatohepatitis (NASH). As several of the drugs used to treat PsA are associated with hepatotoxicity, drug selection can be difficult in patients with PsA and comorbid liver disease. NSAIDs, the DMARD leflunomide, methotrexate, and TNF and JAK inhibitors may lead to hepatotoxicity and abnormal liver function and should be avoided in patients with PsA and liver disease. methotrexate and leflunomide are also associated with the development of MASLD, including NASH.
Compared with the general population, the prevalence of type 2 diabetes is higher in patients with PsA. This is another important consideration regarding treatment options for PsA as medications, including NSAIDs, corticosteroids, and cyclosporine can worsen glycemic homeostasis and negatively affect CV risk.
Patients with PsA may also have a higher prevalence of chronic hepatitis B (HBV) and hepatitis C (HCV) infections and should consult with a hepatologist or gastroenterologist before undergoing treatment for PsA. Screening for HBV and HCV must take place before prescribing methotrexate and biologic DMARDs for patients residing in areas where these infections are endemic.
Mental health disorders such as depression are a significant concern in patients with PsA. The prevalence of depression is higher in patients with PsA compared to patients with psoriasis but without PsA. Because depression is associated with work disability, loss of income, and reduced quality of life, patients should undergo psychiatric assessment and receive appropriate treatment for any mental health issues.