Lana Pine is the editor of HCPLive Rheumatology. She is an experienced editor and technical writer with a demonstrated history of working in the banking and publishing industries. In her free time, she enjoys cooking, yoga, listening to podcasts, and drawing. She can be reached via email at LPine@mjhlifesciences.com.

Lana Pine

What are the main benefits of incorporating PROs into the treatment and management of psoriatic disease?

What are some of the challenges and limitations associated with collecting and using PROs?

What strategies do you find most effective in managing the dual challenges of psoriasis and psoriatic arthritis?

How do you assess the differential impact of psoriasis and psoriatic arthritis on your patients’ quality of life, and what role do PROs play in guiding treatment?

How can the broader healthcare system benefit from incorporating PROs into chronic disease management?

The intersection of dermatology and rheumatology is most evident in instances of 

, which often occur in a single patient simultaneously. The inflammatory conditions are interconnected, with PsA primarily developing among individuals with an established psoriasis diagnosis.

The identification of individuals at risk of PsA development is widely accepted as necessary for clinicians treating those with psoriasis. Scalp and nail psoriasis involvement, as well as inverse psoriasis and one’s cutaneous disease severity, are all known clinical features indicating higher risk among patients of developing PsA.

Around 30% of patients with psoriasis develop PsA at some point in their lives, so the treatment and management of both conditions can quickly become a reality for many patients with 1 condition or the other.

 Treatments approved for these conditions can overlap as well, as is the case of the drugs apremilast (Otezla) and deucravacitinib (Sotyktu).

There may be a wide variety of management strategies implemented by clinicians when working with patients that suffer from psoriatic disease, but it is becoming more widely accepted that patient-reported outcomes (PROs) are essential as an assessment of the usefulness of such strategies and as endpoints for clinical research.

In this feature, 3 experts are featured to discuss the necessity of implementation of PROs in managing both psoriatic diseases.

 editorial team spoke with Raj Chovatiya, MD, PhD, clinical associate professor of medicine for the Rosalind Franklin University of Medicine and Science and founder and director of the Center for Medical Dermatology and Immunology Research in Chicago.

The team also interviewed Amanda Mixon, PA-C, a physician assistant at UCHealth Rheumatology Clinic who specializes in helping patients to manage rheumatologic conditions such as PsA. Lastly, the team spoke with David Chandler, the Chief Executive of the nonprofit organization known as the Psoriasis and Psoriatic Arthritis Alliance (PAPAA).

Chovatiya and Mixon are featured in interviews posted in a video series above. Chandler’s discussion with the editorial team was submitted in writing and posted below. The 3 experts, each with their own approaches to the questions posed, express views which highlight important points about the value of PROs in the management of psoriasis and psoriatic arthritis.

The main advantage is that the psoriatic arthritis patient is playing an active role in their care, this real-world direct patient data that is outside of clinical trials, can provide a physician with important information that perhaps was not recorded or seen as important in a trial.

Some important issues that influence how someone feels, often cannot be seen within the standard validated test, this type of feedback will help to consider ongoing therapy. The notion of patient-centered care and patient-perspective, also plays in here, where what is important, is now recorded and used to influence future care, that has to be seen as an advantage. Communication is also improved, as a patient feels they are part of the process.

What are some of the challenges and limitations associated with collecting and using PROs in clinical practice?

 I suspect that the accuracy and memory recall could provide an issue. Therefore, a baseline needs to be established. Between patient and physician, there could be different reference points that do not correlate with validated tests.

So, over time although pain may be at a similar point as at baseline, the patient may become ‘used to it’ and accept it, therefore not report any worsening, which could be interpreted as improvement. Tracking those could provide useful insight across other patients too.

How can healthcare providers effectively integrate PROs into their routine clinical practice?

 In the UK it will depend on where the patient is being treated, we have a primary care general doctor and secondary care specialist, the latter may be a generalist too. So, for psoriatic arthritis if it is being managed at primary care, the pressure and time may limit the ability to record and enter into such detail, this is not a criticism, but a general recognition of the work load and need to see as many people as possible.

For secondary care, where the likelihood of more severe disease is being managed, the need to monitor benefit is perhaps more important not least due to the potential recommendations made by HTA assessments for cost-effectiveness of drugs. Including PROs in that patient consult, will add to the likely benefit, so using again a baseline and then asking the patient to report back. The important issue is to make sure that this is to aid care and improve outcomes, not limit access due to cost.

What do you see as the future of PROs in the treatment and management of psoriatic disease?

We need real-world data, the lived experience, so making the assessment and follow-up a standard part of care, by demonstrating the benefits could see them as vital. If they become difficult to record and do not help reduce disease symptoms then both patient and physician will be reluctant to use them, unless they become a mandatory part of prescribing, which perhaps would not be a bad thing.

How can policy makers and healthcare organizations encourage the broader adoption of PROs?

 If it can be shown that the use of PROs can improve patient care and reduce the need for constant monitoring and perhaps reduce costs, then policy makers are likely to support the introduction, if not I’m not sure much else will increase enthusiasm.

 In your opinion, what is the overall impact of using PROs on the quality of life and health outcomes for patients with psoriatic disease?

 I think the main impact is that the care process becomes a partnership and the patient feels more in control, by actively monitoring their own outcomes and knowing that could improve their progression is very empowering, the shift from ‘doctor tells, patient does’ to ‘doctor asks patient considers and actively manages’ and reports, particularly how their quality of life has improved, changed or otherwise, can only be a good idea in the management of psoriatic arthritis.

That’s an interesting question. We have limited capacity in the UK, with longer waiting lists and issues with increasing health care cost. Chronic disease probably takes up a huge amount of the capacity.

For psoriatic arthritis and other inflammatory conditions, we know if left untreated there is a potential for joint damage, which could lead to disability and extra care and of course cost. The benefit of managing people early, and reducing the need for constant recalls, could free up capacity and improve the overall benefit to other people. Therefore, those that can be monitored effectively, are.

Gladman DD, Antoni C, Mease P, Clegg DO, Nash P. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005;64 Suppl 2:ii14–ii17.

Zabotti A, Tinazzi I, Aydin SZ, McGonagle D. From Psoriasis to Psoriatic Arthritis: Insights from Imaging on the Transition to Psoriatic Arthritis and Implications for Arthritis Prevention. Curr Rheumatol Rep. 2020 May 16;22(6):24. doi: 10.1007/s11926-020-00891-x. PMID: 32418006; PMCID: PMC7230038.

Wilson FC, Icen M, Crowson CS, McEvoy MT, Gabriel SE, Kremers HM. Incidence and clinical predictors of psoriatic arthritis in patients with psoriasis: a population-based study. Arthritis Rheum. 2009;61(2):233–239.

Gisondi P, Bellinato F, Maurelli M, Geat D, Zabotti A, McGonagle D, Girolomoni G. Reducing the Risk of Developing Psoriatic Arthritis in Patients with Psoriasis. Psoriasis (Auckl). 2022 Aug 10;12:213-220. doi: 10.2147/PTT.S323300. PMID: 35975124; PMCID: PMC9375973.

Videos

This feature highlights the views of 3 experts on the integration of patient-reported outcomes into the management of psoriatic disease.

Harnessing Patient Insights: The Role of PROs in Managing Psoriasis and Psoriatic Arthritis

Results of a post hoc analysis of the VOLTAIRE-RA trial showed patients with moderate to severe 

 treated with either the adalimumab reference product or the 

 adalimumab-adbm had clinically meaningful improvements and similar domain scores at weeks 12 and 24, according to research published in 

.1 Additionally, a high proportion of patients had scores greater than or equal to normative values across treatment arms. This is particularly notable as it was a previously difficult to achieve treatment goal in other RA trials.

“If appropriate long-term treatment is not given, progressive functional impairments can result in reductions in health-related quality of life (HRQoL),” wrote a team of investigators led by Vibeke Strand, MD, associated with the Division of Immunology/Rheumatology at Stanford University School of Medicine. “The most commonly reported RA symptoms associated with negative effects on HRQoL include pain, physical function impairments, fatigue, and morning stiffness. These symptoms also predispose to impaired work productivity and inability to fulfill day-to-day activities.”

With this in mind, it is important to understand the impact of new treatment options, such as adalimumab-adbm, from a patient’s perspective when designing, performing, and reporting on clinical trials.2

VOLTAIRE-RA was a double-blind, phase 3 randomized controlled trial (RCT) that enrolled patients with RA aged 18 – 80 years old who were currently being treated with methotrexate. Eligible participants received 40 mg of the adalimumab reference product or the biosimilar via a subcutaneous injection once every 2 weeks for a 24-week period. Those who were in the reference cohort were re-randomized at week 24 to either continue the reference drug or switch to the biosimilar. Patients in the biosimilar cohort were dummy re-randomized to continue treatment with the biosimilar.

Investigators compared patient-reported outcomes, such as HRQoL, among patients with RA using the 36-Item Short Form Survey (SF-36) physical component summary (PCS) and mental component summary (MCS) as well as domain scores at baseline, week 12, and week 24. Results were defined as clinically meaningful if improvements were greater than or equal to minimum clinically important differences (MCIDs) of 2.5 for the PCS domain score and 5.0 for the MCS domain score. Spydergrams and the health utility SF-6D measure helped to quantify comparisons with age- and sex-matched norms as well as treatment-associated changes in domain scores. The comparisons across treatment arms were descriptive in nature.

Overall, no differences in PCS scores were observed between the biosimilar cohort and the reference cohort at baseline, week 12, or week 24. The reference product was slightly favored at baseline according to MCS scores, and differences at weeks 12 and 24 were comparably reflective of that.

Over 65% of patients in both cohorts had clinically meaningful improvements in PCS scores at weeks 12 and 24. Similarly, 56% reported improvements in MCS scores greater than or equal to MCID at these time points.

Similar proportions of patients treated with the reference product and the biosimilar had scores greater than or equal to age- and sex-matched normative values at week 24 (14 – 39% vs 15 – 36%, respectively) compared with baseline (1 – 17%).

“VOLTAIRE-RA represents the final step of the biosimilarity assessment for adalimumab-adbm versus adalimumab reference product,” investigators wrote. “In parallel with the equivalent efficacy of adalimumab-adbm and adalimumab reference product in VOLTAIRE-RA, substantial benefits were reported across a range of PROs in both treatment groups. Thus, the efficacy and safety profiles of adalimumab-adbm translated into clinically meaningful improvements in patient experience and perception.”

Strand, V., Bender, S. & McCabe, D. Effects of Adalimumab-adbm Versus Adalimumab Reference Product on Patient-Reported Outcomes in Rheumatoid Arthritis: Results from VOLTAIRE-RA. 

 (2024). https://doi.org/10.1007/s40744-024-00687-w

Sanderson T, Morris M, Calnan M, Richards P, Hewlett S. What outcomes from pharmacologic treatments are important to people with rheumatoid arthritis? Creating the basis of a patient core set. Arthritis Care Res (Hoboken). 2010;62:640–6.

Articles

Results showed comparable clinically meaningful improvements in health-related quality of life among patients treated with the adalimumab reference product and biosimilar adalimumab-adbm. 

Adalimumab-adbm, Reference Adalimumab Demonstrate Clinically Meaningful Improvements in RA 

A machine learning (ML) study provided new insights into potential pathways for detection, prevention, and management strategies for arthritis linked to environmental exposures. Findings revealed improving the interpretability of ML models could provide a potent tool for investigators and clinicians to facilitate a deeper understanding of environmental determinants of arthritis, according to a study published in 

Recently, the potential role of heavy metals, particularly cadmium and lead, in the exacerbation of arthritis has been gaining interest. These heavy metals may exacerbate oxidative stress and could lead to sustained inflammation, which is linked to the pathogenesis of 

“Research into the correlation between heavy metals and arthritis remains nascent, and existing studies predominantly rely on traditional statistical methods,” wrote a group of investigators predominantly from the Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine in Shanghai, China. “These conventional approaches often necessitate extensive data requirements, incorporate numerous presumptions, and are subject to stringent application constraints, which restricts their capacity to derive insights from voluminous datasets. However, the dawn of the big data era, coupled with the swift advancement of computational technologies, has paved the way for the burgeoning application of ML techniques across various domains, including medical research.”

Investigators used a phased ML strategy that encompassed a range of methodologies, such as the SHapley Addictive exPlanations (SHAP), and leveraged the minimum absolute shrinkage and selection operator (LASSO) regression, as well as the analytical framework, as well as integrating laboratory, demographic, and questionnaire data, to leverage the advanced ML techniques to understand the relationship between heavy metal exposure and its impacts on RA and OA. Data were collected from the National Health and Nutritional Examination Survey (NHANES) between 2003 and 2020.

A total of 13 ML models were employed across 7 methodologies to increase the predictability and interpretability of clinical outcomes. Each model phase was designed to refine the performance of the algorithm.

Ultimately, 14,319 patients were included in the analysis, of which 49% were male. The average age of participants was 49.0 years, and ranged from 34.0 to 63.0 years.

Results showed significant associations between specific heavy metals, including arsenic, arsenite, arsenic acid, dimethylarsinic acid, monomethylarsonic acid, barium, cadmium, lead, antimony, and tungsten, and an increased risk of arthritis. The phased ML approach allowed for the identification of key predictors and their contributions to disease outcomes.

Investigators noted the lack of a longitudinal follow-up for the same cohort as a limitation of the study. Additionally, the inability to access other datasets of a similar scale was another limitation. Inherent biases of cross-sectional studies, potential information bias as arthritis diagnoses were self-reported, and biases from missing data may have impacted the findings. Additionally, disparities in feature importance between SHAP and the premutation shuffling, with the latter concentrating on global explanations while the former focused on individual prediction contributions, could have hindered replicability because of the complexity of model interpretation.

Aside from heavy metal exposure, age, gender, and ethnicity (such as non-Hispanic Whites) were also identified as significant factors, with these groups demonstrating a higher association with arthritis.

“Employing SHAP enhanced our understanding of the predictive outcomes of these models, providing deep insights into the factors contributing to arthritis,” investigators concluded. “This approach combines advanced analytics with improved interpretability, overcoming the typical ‘black box’ issue in machine learning and enabling a more detailed exploration of the relationship between environmental exposures and health outcomes.”

Fan W, Pi Z, Kong K, et al. Analyzing the impact of heavy metal exposure on osteoarthritis and rheumatoid arthritis: an approach based on interpretable machine learning. 

. 2024;11:1422617. Published 2024 Jul 19. doi:10.3389/fnut.2024.1422617

Smallwood, MJ, Nissim, A, Knight, AR, Whiteman, M, Haigh, R, and Winyard, PG. Oxidative stress in autoimmune rheumatic diseases. 

. (2018) 125:3–14. doi: 10.1016/j.freeradbiomed.2018.05.086

Results showed particular heavy metals increased the risk of arthritis. 

Heavy Metal Exposure Linked to Increased Risk of Arthritis 

Credit: Bogomolets National Medical University

Among a cohort of patients with moderate to severe 

 showed bioequivalence to the reference drug regarding safety, efficacy, and immunogenicity, according to findings from a phase 3 clinical randomized trial published in 

Tumor necrosis factor (TNF) inhibitors, such as etanercept, are commonly used to treat RA as TNF leads to increased pathogenetic gene expression and upregulated production of inflammatory cytokines. In fact, the first biological agent used to treat RA was an anti-TNF-α monoclonal antibody introduced to market more than 2 decades ago. Since then, several TNF inhibitors have been approved and are widely used in clinical practice.

“Etanercept is effective in improving the symptoms and pain levels in people with RA, but long-term monitoring is needed,” wrote a team of investigators led by Valentyna Pekhenko, MD, PhD, associated with the Department of General Practice at Bogomolets National Medical University, Medical Center, in Kyiv, Ukraine. “According to analytical comparisons and studies, the etanercept biosimilar and its reference biologic shown similar therapeutic outcomes. However, there are still relatively few reports on bio-etanercept for the treatment of RA.”

To evaluate the therapeutic equivalence of the etanercept biosimilar and the original etanercept among patients with RA, investigators randomized patients 1:1 to receive 25 mg of either drug twice weekly for 24 weeks. The primary endpoint was the number of patients who achieved an American College of Rheumatology 20% improvement (ACR20) response at the end of the trial. Immunogenicity and safety, as determined by adverse reactions and adverse events, were also evaluated.

A total of 79 patients were placed in the biosimilars cohort and 77 received the reference drug. At the 4-week follow-up period, 82.3% (n = 65) of patients in the biosimilars group and 90.9% (n = 70) in the reference drug group achieved an ACR20 response. No significant difference across treatment arms were observed (

= .16) and no significant differences in adverse reactions or adverse events were reported, regardless of severity. Antibody development was observed in 5.1% (n = 4) of patients at visit 6, 5.0% (n = 4) at visit 9, and 3.8% (n = 3) at visit 11. Results were similar in the reference drug cohort, with 6.4% (n = 5) developing antibodies at visit 6, 6.5% (n = 5) at visit 9, and 4.1% (n = 3) at visit 11. These differences were not significant (

Investigators mentioned limitations of the study including the nonblinded study design, which may have impacted findings. As the reference drug has been on the market for a number of years, its safety and efficacy has been fully validated in premarketing clinical trials using a large body of post-marketing clinical data. The current trial has been designed to meet the objectives of the study, accounting for the clinical needs of patients and the clinical safety of the bio-originator. The generalizability of the findings to other diseases may be limited due to only including patients with RA. The small sample size, the time, and the location of the study may have further hindered representativeness.

“The results of this study add to the current knowledge and understanding of the efficacy, safety, and potential immunogenicity of etanercept in the treatment of RA,” investigators concluded. “The studies demonstrate the high similarity in safety, efficacy and immunogenicity between biosimilar etanercept and [original] etanercept.”

Pekhenko V, Udovitskiy V, Barbukho O. Efficacy, safety and immunogenicity of the biosimilar etanercept compared to the reference formulation original etanercept in patients with rheumatoid arthritis: An open-label, randomized, comparative, multicenter study. 

. 2024;103(30):e39060. doi:10.1097/MD.0000000000039060

Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. JAMA. 2018;320:1360–72

A total of 82.3% of patients in the biosimilars group and 90.9% in the reference drug group achieved an ACR20 response.