Vinod Chandran, MBBS, MD, DM, PhD
Psoriatic arthritis may be associated with excess mortality risk but the current evidence to support excess mortality in psoriatic arthritis is inconclusive. Nevertheless, identifying risk factors for mortality in patients with psoriatic arthritis is important so that modifiable factors could be addressed. Vela et al investigated whether the cumulative pain experienced by psoriatic arthritis patients was associated with increased mortality. Using data from the Danish nationwide registry of biological therapies (DANBIO), the authors showed that although there was a significant association between pain intensity and mortality (odds ratio 1.06 (95%CI 1.02 to 1.10) per 5 VAS unit increase), no association was found when the analyses was adjusted for confounders including age, CRP, joint counts, HAQ score, treatment, and comorbidities. As expected, recent glucocorticoid use, chronic obstructive pulmonary disease, diabetes mellitus, cancer and cardiovascular disease were associated with excess mortality. The results indicate that mortality in psoriatic arthritis is primarily driven by associated comorbidities; holistic management of psoriatic disease should include management of associated comorbidities.
Comorbidities have a major impact on patients with psoriatic arthritis and influence a patient’s quality of life and function as well as treatment response. Neuropsychiatric comorbidities have been less studied in psoriatic arthritis. An intriguing study by Garcia et al indicate that cognitive impairment may be associated with psoriatic arthritis. In a small cross-sectional study, they demonstrated that patients with psoriatic arthritis score worse on the Montreal Cognitive Assessment (MoCA) tool compared to controls, with executive skills, naming, language, and abstraction being most affected. Further research is required to explore whether other comorbidities such as cerebrovascular disease, depression or sleep disturbances explain the cognitive impairment. Depression and anxiety are also associated with reduced likelihood of achieving remission or low disease activity state in psoriatic arthritis. In a study of 743 patients, Wong et al demonstrated that patients with depression or anxiety are less likely to achieve a state of sustained minimal disease activity. These studies once again highlight the management of comorbidities to achieve improved outcomes in patients with psoriatic arthritis.
New data also indicate efficacy of targeted therapy in psoriatic arthritis. In two phase 3 trials funded by LEO pharma, Mease et al report that brodalumab, an interleukin 17 receptor inhibitor that is already available for the treatment for psoriasis, is efficacious in the treatment of psoriatic arthritis. Although the trial was terminated early, pooled data from the two trials showed that higher proportions of patients on 140 mg and 210 mg of brodalumab achieved American College of Rheumatology (ACR)20 response at week 16 compared to placebo group (45.8% and 47.9%, respectively vs. 20.9%; P less than .0001).
There are limited data on treatment withdrawal in patients with psoriatic arthritis. Coates et al investigated whether continued treatment with ixekizumab, an interleukin 17A inhibitor was superior to withdrawing ixekizumab in maintaining minimal disease activity state in patents with psoriatic arthritis. They showed that more patients relapsed rapidly after ixekizumab was withdrawn compared to those continuing ixekizumab treatment. Importantly, >95% of patients who relapsed with treatment withdrawal re-achieved MDA on retreatment with ixekizumab within a median duration of 4.1 weeks. Thus, ixekizumab treatment is best maintained after a patient achieves a state of minimal disease activity. If the treatment needs to be interrupted (e.g., infection, surgery), most patients will re-achieve the state of minimal disease activity on retreatment.
Finally, research continues to demonstrate delayed diagnosis of psoriatic arthritis. Karmacharya et al showed that only 45% of patients receive a diagnosis of psoriatic arthritis by 2 years after symptom onset. This study from the population-based Rochester Epidemiology Project indicates that earlier age of onset of symptoms, the presence of higher body mass index and enthesitis are associated with diagnostic delay. Further education of health care providers and patients with psoriasis about psoriatic arthritis may help reduce diagnostic delay; delayed diagnosis leads to poorer long-term outcomes.