 and comorbid obesity were 2.5 – 3 folds less likely to be in remission or low disease activity (LDA) by composite scores when compared with nonobese patients, according to a study published in 

However, the remission and LDA rates were comparable based on the patients’ opinion. Investigators emphasized patients with comorbid obesity may have different disease profiles and require personalized management of their condition.

Obesity is recognized as an important comorbidity among this patient population. Additionally, it is more prevalent in patients with PsA when compared with the general population or those with rheumatoid arthritis and may be linked to an increased risk of developing PsA among patients with psoriasis. This diagnosis may be associated with a sedentary lifestyle due to musculoskeletal inflammation, pain, and psychological stress from skin disease.

“A few studies have indicated that patients with obesity may be less likely to achieve remission,” wrote a group of international investigators. “Furthermore, weight reduction may improve the achievement of remission for those initiating biological therapies. However, little is known on the effect of obesity on reaching remission/LDA when defined by indices and patients’ opinion.”

Baseline data from Remission/Flare in PsA (ReFlaP; 

), an international multi-center cohort study, was used to evaluate adult patients with PsA from 14 countries. Investigators recruited patients with a PsA duration of ≥2 years and information including demographics, comorbidities, clinical data, and patient-reported outcomes were obtained. Physician-reported and/or a body mass index (BMI) of ≥30 kg/m

 was used to define obesity. Remission or LDA was categorized as Very Low Disease Activity (VLDA), minimal disease activity (MDA), Disease Activity in Psoriatic Arthritis (DAPSA) ≤4/≤14, or by the patient’s opinion. The link between obesity and the presence of either remission or LDA was determined with adjustments in multivariable regression models.

Of the approximately half (49.3%, n = 431) of patients included in the study, 31.6% (n = 136) were obese. Patients categorized as obese were older, more frequently women, had worse pain, physical function, and health-related quality of life, and had higher tender joint and enthesitis counts when compared with nonobese patients.

Patients with obesity were less likely to be in VLDA, DAPSA remission, and MDA with adjusted odds ratios (ORs) of .31(95% confidence interval [CI] .13 to .77); .39 (95% CI .19 to .80), and .61 (95% CI .38 to .99), respectively. However, the rates of DAPSA-LDA and patient-reported remission and LDA were similar among obese and nonobese patients.

Investigators noted limitations including the choice to recruit patients from tertiary referral centers, which may have hindered the generalizability of the results. Additionally, the cross-sectional analysis did not allow the study to evaluate changes in remission status or casualty. The small sample size of patients also precluded longitudinal analysis. Information collected did not exclude patients with obesity and high disease activity at baseline, who may have been effectively treated with a treat-to-target strategy. Variables, including fibromyalgia, were unaccounted for and may have been an important interaction with obesity. Lastly, obesity was defined as either clinician report or BMI, which may have led to a certain number of discrepancies.

“PsA patients with concurrent obesity had lower odds of being in remission by indices, highlighting the importance of managing obesity to improve the care of patients with PsA,” investigators concluded. “Shared decision-making is important for an individualized target of management.”

Leung YY, Eder L, Orbai AM, Coates LC, de Wit M, Smolen JS, Kiltz U, Palominos P, Canete JD, Scrivo R, Balanescu A, Dernis E, Meisalu S, Soubrier M, Kalyoncu U, Gossec L. Association between obesity and likelihood of remission or low disease activity status in psoriatic arthritis applying index-based and patient-based definitions of remission: a cross-sectional study. RMD Open. 2023 Sep;9(3):e003157. doi: 10.1136/rmdopen-2023-003157. PMID: 37709527; PMCID: PMC10503343.

Setty AR, Curhan G, Choi HK. Obesity, waist circumference, weight change, and the risk of psoriasis in women: nurses' health study II. Arch Intern Med 2007;167:1670–5. doi:10.1001/archinte.167.15.1670

Articles

Patients diagnosed with psoriatic arthritis and obesity were older, more frequently women, had worse pain, physical function, and health-related quality of life, and had higher tender joint and enthesitis counts when compared with nonobese patients. 



Patients with PsA and Comorbid Obesity Less Likely to be in Remission 

New results from a systematic review of randomized clinical trials suggest adult patients with 

 exhibited comparable hepatic safety profiles following treatment with either febuxostat or allopurinol.

The review of 11 trials reported most hepatic safety parameters assessed in adult patients with gout did not show statistically significant differences between allopurinol and febuxostat treatment, aligning with previous analyses of liver damage risk associated with each medication.

“An accurate description of the hepatic safety profile of allopurinol and febuxostat will assist healthcare practitioners in determining appropriate liver monitoring for patients receiving these medications for the management of gout,” wrote the investigative team, led by Neily Zakiyah, MSc, PhD, department of pharmacology and clinical pharmacy, faculty of pharmacy, Universitas Padjadjaran.

Allopurinol is a xanthine oxidase inhibitor typically initiated at a starting dose of 100 mg/day, with an effect daily dose generally around 300 mg. Febuxostat is a non-purine selective inhibitor of xanthine oxidase, selectively inhibiting the enzyme to reduce serum uric acid levels.

Extensive clinical trial data have reported the strong efficacy and safety of febuxostat and allopurinol as urate-lowering therapies for patients with gout. In particular, the optimal control of serum uric acid levels can also reduce the clinical and financial burden linked to gout.

However, despite reports on the superior clinical efficacy of febuxostat compared to allopurinol, there is a lack of systematic analysis data on the comparable hepatic safety of the medications in adult patients with gout. Zakiyah and colleagues performed a systematic review of PubMed, Cochrane Library, and Scopus until May 2023 to gather relevant data and assess hepatic safety.

Eligibility criteria included any published randomized controlled trials involving adult patients with gout comparing allopurinol and febuxostat reporting liver function safety results. The collected studies included assessments on liver function outcomes that outweigh the upper limits normal. Assessment of the effects in the study focused on hepatotoxicity and liver function outcomes.

To ensure the accuracy of selection, 2 reviewers independently screened articles during both initial title-and-abstract and full-text screening. A Jadad score was used to evaluate the quality of studies to determine the validity of eligible randomized controlled trials. It comprised 3 components: randomization, blinding, and extent of loss to follow-up.

A total of 619 citations were identified in the 3 databases and 512 publications were screened. After applying inclusion and exclusion criteria, investigators identified 11 studies that met the criteria and were included in the review. Of these 11 studies, 9 were double-blind randomized clinical trials.

Baseline demographics showed the study population mostly comprised male patients aged ≥18 years, mirroring the known higher prevalence of gout in males over 40 years. The patient population included in trials comparing febuxostat and allopurinol was 7810 patients, ranging from daily low doses (10/20 mg) and high doses (240 mg) of febuxostat, compared to daily allopurinol (50/100 to 600 mg).

Upon analysis, investigators observed consistent adverse events in liver function for both febuxostat and allopurinol. The majority of included studies did not show statistically significant differences in hepatic safety data between febuxostat and allopurinol. Often, adverse events resulted in study withdrawal, but most elevations in liver function parameters were mild to moderate in severity.

Investigators noted a particular study showed significant differences in abnormal liver function test results, which were the most frequent adverse event leading to subject withdrawal. Comparisons between 120 mg febuxostat (2.79%) and the allopurinol group (0.4%) showed statistical significance (

 = .04). However, most adverse events were assessed as mild to moderate and reversible after discontinuation of febuxostat.

Given the small number of patients involved in clinical trials investigating febuxostat and allopurinol, Zakiyah and colleagues suggest the importance of continuous monitoring of pharmacovigilance databases and conducting future pharmacoepidemiology studies.

“Conducting future pharmacoepidemiology studies to explore the hepatic safety data of allopurinol and febuxostat is of utmost importance, given their frequent use by patients to treat this chronic disease,” investigators wrote. “Such studies would be highly beneficial for ensuring patient safety and understanding any potential risks associated with these medications.”

Dewi C, Puspita F, Puspitasari IM, Zakiyah N. Hepatic Safety of Febuxostat and Allopurinol for Gout Patients: A Systematic Review of Randomized Controlled Trial. Ther Clin Risk Manag. 2023;19:731-743. Published 2023 Sep 18. doi:10.2147/TCRM.S424598

Suzuki S, Yoshihisa A, Yokokawa T, et al. Comparison between febuxostat and allopurinol uric acid-lowering therapy in patients with chronic heart failure and hyperuricemia: a multicenter randomized controlled trial. 

. 2021;49(12):030006052110627. doi:10.1177/03000605211062770

A systematic review of 11 randomized clinical trials found adults with gout exhibited similar hepatic safety profiles for both febuxostat and allopurinol treatment. 

Febuxostat, Allopurinol Show Comparable Hepatic Safety in Patients with Gout

Sexual and gender minority (SGM) individuals with 

chronic inflammatory skin diseases (CISDs)

 are disproportionately impacted by cost-related and non-cost-related obstacles when seeking care, according to new findings, with the prevalence being especially high among non-Hispanic Black or Hispanic/Latino individuals.

This new research was conducted to analyze the existence of such barriers based upon demographic data as well as SGM status. The investigators also sought to compare the prevalence of obstacles related and unrelated to cost for SGM and for non-SGM individuals.

The investigators noted that there is limited data on barriers to health care for those who are SGM and also have CISDs, though recent research did indicate a disproportionate burden of such obstacles for those who identify as Hispanic, non-Hispanic Black, Latino, or of Spanish origin.

 To address the lack of data, the new study was led by Michael R. Nock, BA, from the Department of Dermatology at Yale School of Medicine in New Haven, Connecticut.

“...(In) this study, we used survey data from participants in the National Institutes of Health’s All of Us Research Program to investigate the prevalence of cost and non-cost barriers to care among SGM and non-SGM patients with CISDs,” Nock and colleagues wrote.

The research team used a cross-sectional design for the study, assessing data gathered from participants that had CISDs who had also joined the All of Us Research Program in the period between May 2017 and July 2022. The Program was known to be open to all adults from the US aged 18 or olde who were also not incarcerated and who were able to give consent.

Subjects for the study were recruited either online or as a result of actions by healthcare provider organizations found all across the US. The team followed the reporting guidelines required for survey studies.

Study subjects with reported CISDs were identified by the investigators through the use of specific medical codes that related to skin conditions such as psoriasis, rosacea, and hidradenitis suppurativa. They then grouped the participants into SGM if they had identified with such identities related to gender, sex assigned at birth, or sexual orientation.

Subjects that did not identify with such identities were placed into the category of non-SGM participants, and all were also put into groups that were based upon their self-reported race and ethnicity data.

Once the investigators took into account the data from the participants' demographics, they assessed the existence of barriers to patient health care which were shown to be based on SGM status. They notably considered a range of different obstacles to care, including ones which related to costs and other factors.

To assess these barriers to care, the research team utilized data drawn from the Health Care Access and Utilization Survey. The Survey covered subjects’ experiences in the year prior to the new survey.

Overall, the investigators identified 19,743 subjects that were shown to have CISDs, and 1877 of these individuals identified as SGM. The SGM participants’ mean age was also noted as 40.5, with 64.2% having been assigned female at birth.

Additionally, the research team found that 17,866 of the subjects were found to be non-SGM and they had a mean age 57.1, with a total of 73.9% being assigned female at birth.

Those in the SGM arm that had CISDs, when compared to non-SGM subjects, had a higher rate of delaying mental health care (1.62 times more likely), specialist care (1.23 times more likely), and filling of prescriptions (1.30 times more likely) as a result of cost-related issues.

The investigators also found that they were more likely to delay health care as a result of transportation problems (1.49 times more likely) and not having a practitioner with shared background characteristics. Additionally, they found that SGM individuals reported a greater likelihood of not always being given the respect by their practitioners (1.47 times more likely) versus non-SGM subjects.

“By universally collecting this demographic information from all patients and taking the time to better understand the unique background, values, and goals of each of their patients, dermatologists can be better prepared to provide culturally responsive care to SGM patients with CISDs,” they wrote.

Nock MR, Kamal K, Zampella JG, Roberson ML, Cohen JM, Barbieri JS. Barriers to Care Among Sexual and Gender Minority Individuals With Chronic Inflammatory Skin Diseases in the US. JAMA Dermatol. Published online September 27, 2023. doi:10.1001/jamadermatol.2023.3328.

Nock MR﻿, Barbieri JS﻿, Krueger LD﻿, Cohen JM﻿. Racial and ethnic differences in barriers to care among US adults with chronic inflammatory skin diseases: A cross-sectional study of the All of Us Research Program. J Am Acad Dermatol. 2023;88(3):568-576. doi:10.1016/j.jaad.2022.09.054.

This study also found a particularly high rate of such obstacles for SGM patients who also identify as being either non-Hispanic Black or Hispanic/Latino.


Health Barriers Identified for Sexual, Gender Minority Patients with Chronic Inflammatory Skin Diseases

Results of an online survey showed the prevalence of COVID-19 was low among patients with 

 and participants were generally satisfied with their care during the pandemic, according to a study published in 

 Further, most patients would continue using virtual care for the duration of the pandemic.

The COVID-19 pandemic generated a significant increase in telehealth visits. This in turn created a need for more real-world data on whether virtual care is an acceptable alternative to in-person care for patients with PsA. Studies such as this can aid in developing and implementing patient-informed virtual care to maintain positive relationships between clinicians and patients and ultimately reduce poor outcomes.

“Immune-mediated inflammatory diseases (IMIDs), such as PsA, and their medications were investigated early in the pandemic to determine if they impacted COVID-19 infection risk and severity,” wrote Ashish J Mathew, MD, PhD, associated with the Psoriatic Arthritis Program at the University Healthy Network, University of Toronto, Canada, and colleagues. “Through a large cross-sectional case-reporting registry, the COVID-19 GlobalRheumatology Alliance demonstrated that patients with rheumatic disease tend to have similar or only slightly poorer COVID-19 outcomes compared to non-rheumatic disease populations.” 

To evaluate the prevalence of COVID-19 infection among this patient population, assess the patient’s perspective of risk of infection, and determine the standard of virtual care offered in the early phases of the pandemic, investigators submitted an online survey to patients between June and September 2021. Originally, 600 patients were emailed, 378 did not respond, and 41 provided consent but did not complete the survey. In total, 79% (n = 152/192) of patients completed the survey.

The mean age of participants was 58 years, mean disease duration was 19 years, and 57% were men. The mean patient-reported symptom severity was 4.1 for joint, 3.2 for skin, and 3.7 overall. Most (74%, n = 86) patients would accept the impact of their PsA over the past for the next few months.

Of the 70 patients tested for COVID-19, 4 tested positive. Of these patients, all were admitted to the hospital and 2 required oxygen. Almost all (99%, n = 151) patients received ≥1 vaccine dose and 39% (n = 59) believed medications to treat their rheumatic disease increased their risk of acquiring COVID-19. Of the 130 who participated in a telemedicine assessment, 83% were happy with the consultation. Additionally, most were willing to continue with virtual consultations until the pandemic resolved. On a 10-point scale, the average satisfaction level with pandemic care was 7.9.

Although the study was one of the few including the patient perspective among those with PsA, investigators noted certain limitations. These included the online distribution method and the dependence on email communication. Therefore, patients without access to email were inherently excluded. Additionally, many patients who were emailed did not respond. Further, the sample size was not large enough to accurately capture COVID-19 infection disease data. Lastly, the study was conducted prior to the Omicron and other variants emerged.

“This study provides updated data on patient perspectives following the release of initial scientific data on IMIDs and COVID-19 infection risk and severity. COVID-19 prevalence was low among our patients,” investigators concluded. “The prevalence of patient concerns surrounding the impact of IMIDs and targeted medications should continue to be explored for the risk of behaviors such as stopping medications.”

Pirouzmand N, Pereira D, Sutton M, Mathew AJ, Chandran V, Gladman DD. Psoriatic Arthritis And Covid-19 - Patient Perspectives In A Large Psoriatic Arthritis Cohort [published online ahead of print, 2023 Sep 1]. 

. 2023;jrheum.2022-1265. doi:10.3899/jrheum.2022-1265

Al-Abri R, Al-Balushi A. Patient satisfaction survey as a tool towards quality improvement. Oman Med J 2014;29:3-7

Of the 130 patients with psoriatic arthritis who participated in a telemedicine assessment, 83% were happy with the consultation. 

Most Patients with PsA Satisfied with Virtual Care During COVID-19

New research led by Suvi Virtanen, PhD, suggests that antidepressants do not induce mania or hypomania in pediatric patients with unipolar depression.

Prior to this research, there were few studies on the effects of antidepressants on children and adolescents with unipolar depression. Investigating these rare outcomes, such as incident mania, has been challenging in randomized clinical trials (RCTs).

The investigators used nationwide data from Sweden to examine incident mania or hypomania in pediatric patients. They conducted an observational study with a 12-week time frame, extending it by 4 weeks to account for potential slower medication titration in children.

Participants in the study were aged 4-17 and diagnosed with unipolar depression. They underwent a "washout period" where they didn't take antidepressants for a year before the depression diagnosis, except for those with a prior mania diagnosis.

The treatment group included participants who took antidepressants within 90 days of diagnosis, while the control group did not take antidepressants during that period.

At 12 weeks, the cumulative incidence of mania/hypomania was 0.26% in the treatment group and 0.20% in the control group. By 52 weeks, these figures increased to 0.79% and 0.52%, respectively. Boys in the treatment group had a slightly higher risk of mania.

Antidepressants do not induce mania or hypomania for pediatric patients with 

In a new study led by Suvi Virtanen, PhD, of the department of medical epidemiology and biostatistics at Karolinska Institutet in Stockholm, an international team of investigators wanted to see if antidepressants cause mania or hypomania in pediatric patients with unipolar depression.

Previously, there had been few studies on children and adolescents on this topic. “It is critical to understand potential risks related to anti- depressants in pediatric patients, but rare outcomes, such as incident mania, are difficult to investigate in randomized clinical trials (RCTs),” investigators wrote. “RCTs often have insufficient sample sizes and strict inclusion criteria, which correspond poorly with the characteristics of the population actually receiving the medication in clinical practice.”

The investigators used nationwide data registered in Sweden from July 2006 - December 2019 to investigate incident mania or hypomania in pediatric patients. The investigators also drew their research from other sources, such as the National Patient Register for diagnoses research and the Prescribed Drug Register for prescribed drugs.

The investigators ran an observational study that had a 12-week time frame—they added an extra 4 weeks to The International Society for Bipolar Disorders Task Force’s customary 9 weeks to “account for a potentially slower titration schedule in pediatric patients.”

For the study, the investigators identified participants who had an increased risk of developing mania. The study cohort had participants aged 4-17 years old, all diagnosed with unipolar depression. Participants went through a “washout period” where they did not take any antidepressants for a year prior to their depression diagnosis—although this excluded participants with a prior mania diagnosis.

While the treatment group consisted of participants who took antidepressants within 90 days of the diagnosis, the control group did not take any antidepressants within 90 days of the diagnosis.

By 12 weeks, the estimated cumulative incidence of mania/ hypomania was 0.26% in the treatment group and 0.20% in the control group.

Yet, by 52 weeks, the treatment group rose to 0.79% and the control group went up to 0.52%. Virtanen and colleagues found boys in the treatment group had a higher risk of mania than the girls. Investigators found that there was no evidence that proved antidepressants increased the risk of mania.

“The risk was similar in treatment and control groups by 12 weeks, which is the time window during which treatment-emergent mania is expected to occur,” investigators wrote. “We found a small risk difference only in the longer follow-up analysis, suggesting that the risk increase may be attributable to factors other than the medication.”

In an editorial accompanying the study, authors Krista Huybrechts, MS, PhD, of the division of pharmacoepidemiology and pharmacoeconomics in the department of medicine at Brigham and Women’s Hospital and Harvard Medical School, and Mark Olfson, MD, MPH, of the department of psychiatry in the College of Physicians and Surgeons at Columbia University and New York State Psychiatric Institute, provided additional context to the meaning of Virtanen and colleagues’ findings.

“The risk difference…provides important additional context from a public health point of view: the 29% increased risk on the relative scale corresponds to the 0.06 excess cases per 100 patients treated,” Huybrechts and Olfson wrote. “While this is not trivial considering the large number of children being treated with antidepressants, it nevertheless provides an important context when considering the risk-benefit trade-off.”

Huybrechts and Olfson found the study “reassuring” since it confirmed that manic episodes in children and adolescents occur at an equal frequency, whether they take antidepressants or not.

The study’s results conflict with a previous register-based study, which found that pediatric patients with unipolar depression, who were treated with antidepressants, had a substantially increased risk of mania.

This new study, however, used a target trial emulation framework to minimize common biases in observational cohort studies. While the previous studies followed up with patients up to 5 years and excluded outcomes within the first 2 months, the new study used a shorter follow-up period of 12 weeks.

The investigators said the study’s strength was its large size and target trial emulation framework, while the limitations were that the findings apply primarily to selective serotonin reuptake inhibitors, and therefore they did not have information on medication dosing.

“Similarly to RCTs, our cohort study found incident mania to be rare in the clinical practice setting,” investigators concluded. “Furthermore, RCTs have found no clear evidence of antidepressants increasing the risk of mania compared with placebo.”

Virtanen S, Lagerberg T, Takami Lageborn C, et al. Antidepressant Use and Risk of Manic Episodes in Children and Adolescents With Unipolar Depression [published online ahead of print, 2023 Sep 27]. JAMA Psychiatry. 2023;10.1001/jamapsychiatry.2023.3555. doi:10.1001/jamapsychiatry.2023.3555

Huybrechts KF, Olfson M. Evaluating the Liability of Antidepressants to Induce Mania in Children and Adolescents With Depression [published online ahead of print, 2023 Sep 27]. JAMA Psychiatry. 2023;10.1001/jamapsychiatry.2023.3525. doi:10.1001/jamapsychiatry.2023.3525

New data from Sweden conflict with previous register-based research showing a “substantially” increased risk of mania among antidepressant-treated pediatric patients with unipolar depression.

Antidepressants Do Not Increase Risk of Mania in Children and Adolescents

Both interleukin (IL)-23 and IL-17 inhibitors are linked to a diminished risk of colorectal, non-Hodgkin lymphoma (NHL), hepatobiliary, melanoma, ovary cancers, and basal cell carcinoma (BCC) as compared with tumor necrosis factor inhibitors (TNFi) for those with 

This new data resulted from a global study conducted to assess psoriasis patients’ malignancy risk once treated with IL-23 and IL-17 inhibitors, specifically in comparison to those with TNFi prescriptions in the initial 5 years after drug initiation.

This new research was led by Khalaf Kridin, MD, PhD, from Lűbeck Institute of Experimental Dermatology at the University of Lübeck in Germany. Kridin and colleagues sought to resolve the methodological issues they had observed in studying risk of cancer with a longer-term study, given issues such as the extended time the development of malignancies can take.

“The aim of the current study is to assess the risk of a wide assortment of malignancies in a large cohort of patients with psoriasis starting IL-23i and IL-17i treatment relative to those undergoing tumor necrosis factor inhibitor (TNFi) therapy during the first 5 years following treatment initiation,” Kridin and colleagues wrote.

The investigators used a retrospective cohort design and utilized the TriNetX database to examine patients’ risk of malignancies in patients with psoriasis starting 3 different biologic agents. The database is known to be a comprehensive health research network, with data on about 117.5 million individuals over 91 healthcare organizations.

The research team screened medical records, specifically those of 117.5 million health-insured patients within the Global Collaborative Network (GCN) of TriNetX for psoriasis diagnostic codes. Three different treatment arms were created by the team and based upon the biologics used in the study: TNFi, IL-17i, and IL-23i.

Participants in the IL-17 inhibition arm were given ixekizumab, secukinumab, or brodalumab. Those in the IL-23 inhibition arm were given guselkumab, risankizumab, or tildrakizumab. TNFi arm participants received infliximab, adalimumab, certolizumab pegol, or etanercept.

The investigators’ criteria were applied to prevent overlapping exposures to several different treatment classes among the participants. The subjects were later followed over the course of 5 years in order to examine their risk of hematologic and solid malignancy development.

The research team conducted propensity score matching to balance their study arms in terms of comorbidities, previous treatments, demographic data, and other possible confounding variables. Further sensitivity analyses were planned by the team to assess the subjects’ risk of malignancies for those managed by IL-17 and IL-23 inhibitors versus biologic-naïve individuals, with matching leading to uniform distribution of the confounding variables across the study arms.

Overall, the investigators reported that those prescribed IL-17 inhibitors ended up showing a lowered risk of several different types of cancers. These malignancies included hepatobiliary cancer (HR, 0.68; 95% CI, 0.58-0.80; P<0.001), colorectal cancer (HR, 0.68; 95% CI, 0.49-0.95; P=0.024), and NHL (HR, 0.58; 95% CI, 0.40-0.82; P=0.002).

Additional malignancies noted by the research team which had lower risk included melanoma (HR, 0.52; 95% CI, 0.37-0.73; P<0.001), ovary cancer (HR, 0.48; 95% CI, 0.29-0.81; P=0.005), and basal cell carcinoma (BCC; HR, 0.57; 95% CI, 0.48-0.67; P<0.001).They found that IL-23 inhibitors were linked to a diminished risk of hepatobiliary cancer (HR, 0.44; 95% CI, 0.31-0.62; P<0.001), NGL (HR, 0.39; 95% CI, 0.19-0.78; P=0.006), and BCC (HR, 0.76; 95% CI, 0.57-0.99; P=0.046).

The investigators’ sensitivity analysis compared subjects that had been treated with IL-17 and IL-23 inhibitors to individuals who were biologic-naïve and this showed a lowered risk of several different types of malignancies linked with these classes of medications.

“The current study sheds important light on the long-term safety of IL-17i and IL-23i with regard to carcinogenesis,” they wrote. “The safety of this class should be further investigated among patients with a prior history of malignancies before drug initiation.”

Kridin, K., Abdelghaffar, M., Mruwat, N., Ludwig, R.J. and Thaçi, D. (2023), Are interleukin 17 and interleukin 23 inhibitors associated with malignancies? – Insights from an international population-based study. J Eur Acad Dermatol Venereol. Accepted Author Manuscript. https://doi.org/10.1111/jdv.19520.

Garcia-Doval I, Descalzo MA, Mason KJ, Cohen AD, Ormerod AD, Gómez-García FJ, et al. Cumulative exposure to biological therapy and risk of cancer in patients with psoriasis: a meta-analysis of Psonet studies from Israel, Italy, Spain, the U.K. and Republic of Ireland. Br J Dermatol [Internet]. 2018 Oct 1 [cited 2022 Oct 24];179(4):863–71. Available from: https://pubmed.ncbi.nlm.nih.gov/29723914/.

This new data should be taken into account before biologics prescriptions are made for patients with conditions such as psoriasis.


IL-23, IL-17 Inhibitors Associated with Lower Risk of Several Malignancies Compared to TNFi

New data from a National Institutes of Health-funded study are underlining the potential of ultrashort echo time (UTE) magnetic resonance imaging (MRI) techniques for quantitative evaluation of entheses and tendons in patients with 

Led by investigators from the University of California, San Diego (UCSD), results of the study indicate using MRI T1 and magnetization transfer (MT) modeling could aid in early detection and management of PsA, with use of UTE-MT modeling able to detect increased entheses among those with PsA.

“The current study was the first to examine UTE-MT modeling for in vivo enthesis evaluation, and we have also demonstrated its potential for distinguishing between patients with PsA and asymptomatic volunteers,” investigators wrote.

With advances in imaging driving a growing interest in use of imaging modalities to improve early detection of PsA,

 the current study was led by Dina Moazamian, MD, and a team of investigators to better understand the potential for UTE-MRI in the evaluation of the Achilles tendon and enthesis. With this in mind, the investigators designed their study to evaluate potential differences in macromolecular proton fraction (MMF) of the Achilles tendon between patients with and without PsA as the primary outcome of interest.

To assess MMF, investigators performed scans of the sagittal plane with UTE-T1 and UTE-MT modeling sequences on a 3-T clinical scanner. For the purpose of analysis, Mann–Whitney-U tests were used to estimate differences between the PsA and asymptomatic cohort.

For inclusion in the study, patients needed to be aged 19-90 years without a history of trauma to the ankle. The control group of asymptomatic patients consisted of volunteers from the UCSD campus with no ankle symptoms of any sort and the PsA cohort consisted of consecutive patients referred from the UCSD rheumatology clinic with a diagnosis of PsA.

A total of 26 patients with PsA and 27 asymptomatic volunteers were included in the study. The cohort of PsA patients had a mean age of 59 (standard deviation [SD], 15) years and 41% were female. The cohort of asymptomatic patients had a mean age of 33 (SD, 11) years and 47% were female.

Upon analysis, results indicated UTE-T1 in the entheses was significantly greater for those with PsA relative to the asymptomatic group (967; SD, 145 vs 872; SD, 133 ms; 

<.01) and UTE-T1 in the tendons was also significantly greater for the PsA group relative to the asymptomatic group (950; SD, 145 vs 850; SD, 138 ms; 

<.01). Further analysis suggested MMF in the entheses was significantly reduced for those with PsA relative to the asymptomatic group (15%; SD, 3% vs 18%; SD, 3%; 

.01) and MMF in the tendons was also significantly reduced for those with PsA group relative to the asymptomatic group (17%; SD, 4% vs 20%; SD, 5%; 

Analysis of percentage differences revealed differences in MMF between the study groups, which were -16.6% and -15.0% for the enthesis and tendon, respectively, were greater than those observed for T1 differences, which were 10.8% and 11.7% for the enthesis and tendon, respectively.

Investigators called attention to multiple limitations within their study to consider when interpreting findings. These included the low number of patients, increased age of PsA patients relative to asymptomatic volunteers, and an inability to identify and exclude patients who may have been under treatment for PsA.

“Significantly higher UTE-T1 and lower MMF values were found in the entheses and tendons of PsA patients compared with asymptomatic volunteers. This study highlights the potential of UTE-T1 and UTE-MT modeling for quantitative evaluation of entheses and tendons in PsA patients,” investigators wrote.

Moazamian D, Athertya JS, Dwek S, et al. Achilles tendon and enthesis assessment using ultrashort echo time magnetic resonance imaging (UTE-MRI) T1 and magnetization transfer (MT) modeling in psoriatic arthritis [published online ahead of print, 2023 Sep 23]. 

Mathew AJ, Coates LC, Danda D, Conaghan PG. Psoriatic arthritis: lessons from imaging studies and implications for therapy. 

. 2017;13(2):133-142. doi:10.1080/1744666X.2016.1215245

A study from UCSD highlights how advances in imaging modalities and utilization could aid in the early detection of psoriatic arthritis. 

Ultrasound and MRI of Achilles Tendon Can Improve Early Detection of Psoriatic Arthritis

 infection (CDI) increased during the COVID-19 pandemic, according to findings from a study evaluating excess gastrointestinal, liver, and pancreatic disease deaths in the US.

Results showed more than 5,000 excess deaths from CDI, equating to 35.6% excess risk compared to the expected number of deaths during the study time frame.

“Previous evidence has indicated patients with digestive-related abnormalities were vulnerable to the pandemic, not only because of their higher mortality risk of COVID-19, but their unmet healthcare needs due to the overwhelmed healthcare services,” wrote investigators.

 “However, few studies have quantified the impact of the pandemic on individuals with digestive diseases. There is also limited research examining the excess deaths associated with digestive diseases during the pandemic.”

The US Centers for Disease Control and Prevention estimates 

 causes almost 500,000 infections in the US each year, with severe cases requiring hospitalization.

 People who are immunocompromised, or whose immune system is weakened by medication, are more susceptible to serious illness from COVID-19, which may include those affected by gastrointestinal, liver, and pancreatic diseases.

 Beyond infection, the COVID-19 pandemic also stressed hospital systems and negatively affected health care and public health infrastructures, potentially limiting access to treatment for other illnesses.

Jinjun Ran, PhD, associate professor at Shanghai Jiao Tong University School of Medicine in China, and a team of investigators sought to examine excess deaths related to gastrointestinal, liver, and pancreatic diseases during the COVID-19 pandemic by retrieving weekly provisional death counts from the National Vital Statistics System between January 2018 and February 2020, which provided investigators with information related to demographic information as well as cause of death. Using a quasi-Poisson regression model, investigators planned to estimate the expected deaths from March 2020 to September 2022.

Investigators selected the dominant causes of death relevant to the digestive system, including gastrointestinal hemorrhage, ulcers, paralytic ileus and intestinal obstruction, vascular disorders of the intestine, 

 colitis, esophageal cancer, gastric cancer, colorectal cancer, alcoholic liver disease, fibrosis/cirrhosis, chronic hepatitis C, hepatic failure, liver and intrahepatic bile duct cancer, acute pancreatitis, and pancreatic cancer. Excess death counts were calculated by subtracting expected death counts from observed death counts, excess mortality by excess death counts divided by population size, and excess risk by excess death counts divided by expected death counts.

Both underlying and contributing causes of death assigned to digestive diseases were considered. Aggregated data were stratified by cause of death, age, sex, race, ethnicity, and state.

Investigators noted the greatest excess death counts were 22,156 (95% confidence interval [CI], 21,478 to 22,504) for gastrointestinal hemorrhage, 17,531 (95% CI, 16,936 to 17,837) for alcoholic liver disease, and 10,741 (95% CI, 9930 to 11,157) for fibrosis/cirrhosis.

CDI had the most significant increased death risk across all disease types (excess risk [ER], 35.9%; 95% CI, 34.1% to 37.8%). For gastrointestinal diseases, hemorrhage (ER, 24.8%; 95% CI, 24.0% to 25.5%), ulcers (ER, 15.1%; 95% CI, 13.6% to 16.7%), and colorectal cancer (ER, 3.4%; 95% CI, 2.9% to 3.9%) also had notable death risks. For liver and pancreatic diseases, acute pancreatitis had the largest ER (20.6%, 95% CI, 18.9% to 22.4%), followed by alcoholic liver disease (19.9%, 95% CI, 19.2% to 20.6%), chronic hepatitis C (15.1%, 95% CI, 13.9% to 16.3%), fibrosis/cirrhosis (8.5%, 95% CI, 7.9% to 9.1%), and hepatic failure (7.1%, 95% CI, 6.4% to 7.9%).

Investigators pointed out ERs for gastrointestinal diseases were higher among adults aged 20-64 years compared to adults aged 65-84 years, particularly for gastrointestinal hemorrhage (38.7% vs 26.2%), ulcers (23.4% vs 9.8%), and CDI (54.7% vs 39.6%). Higher ERs of liver disease were also more prevalent among young adults, including alcoholic liver disease (23.0% vs 15.9%), fibrosis/cirrhosis (16.0% vs 6.8%), and hepatic failure (13.0% vs 4.6%).

Investigators also noted disproportional ERs were observed upon stratification by race and ethnicity. The ER of CDI was 49.2% (95% CI, 42.8% to 55.7%) among non-Hispanic Blacks, −0.2% (95% CI, −5.5% to 5.4%) among Hispanic participants, and 37.2% (95% CI, 35.1% to 39.4%) among non-Hispanic Whites. The ERs of alcoholic liver disease in non-Hispanic Blacks, Hispanics, and non-Hispanic Whites were 27.4%, 23.6%, and 16.8%, respectively. The ERs in Hispanics and non-Hispanic Whites were 27.1% and 14.0%, respectively, for chronic hepatitis C, 23.6% and 7.2%, respectively, for fibrosis/cirrhosis, and 13.4% vs. 6.7%, respectively, for hepatic failure.

The ERs of most gastrointestinal, liver, and pancreatic diseases were more pronounced in Wave II and highest in Wave IV, which were defined by investigators as June 2020 to October 2020 and June 2021 to November 2021, respectively. Of note, CDI showed a persistently increasing trend throughout the entire pandemic.

“As SARS-CoV-2 may continually circulate in the community and lead to potential epidemic waves in the future, it is important for pertinent stakeholders to further evaluate the long-term impact of the pandemic on healthcare workers and patients,” investigators concluded.

 “It is also necessary to develop sustainable strategies to improve the diagnostic, treatment, and disease management capacities of patients with GI, liver, and pancreatic conditions in the era of living with COVID-19.”

Han L, Shi H, Li Y, et al. Excess Deaths of Gastrointestinal, Liver, and Pancreatic Diseases During the COVID-19 Pandemic in the United States. 

 68:1606305. doi:10.3389/ijph.2023.1606305

Centers for Disease Control and Prevention. What is C. diff? C. diff (Colstridioides difficile). Accessed September 26, 2023. 

Centers for Disease Control and Prevention. Factors That Affect Your Risk of Getting Very Sick from COVID-19. COVID-19. May 11, 2023. Accessed September 26, 2023. 

https://www.cdc.gov/coronavirus/2019-ncov/your-health/risks-getting-very-sick.html

Centers for Disease Control and Prevention. Impact of Hospital Strain on Excess Deaths During the COVID-19 Pandemic — United States, July 2020–July 2021. Morbidity and Mortality Weekly Report. November 19, 2021. Accessed September 26, 2023. 

https://www.cdc.gov/mmwr/volumes/70/wr/mm7046a5.htm

Findings revealed more than 5,000 excess deaths from CDI and 35.6% excess risk compared to the expected number of disease deaths calculated using data from the National Vital Statistics System. 

C Diff Deaths Increased During COVID-19 Pandemic, Study Finds

FDA approves phentolamine ophthalmic solution (RYZUMVI) 0.75% for pharmacologically-induced mydriasis produced by adrenergic agonists or parasympatholytic agents. 

It is expected to become commercially available in the US in the first half of 2024

The percentage of eyes in the MIRA clinical trial program returning to ≤0.2 mm from baseline pupil diameter was statistically significantly greater in the phentolamine ophthalmic solution group versus placebo. 

The US Food and Drug Administration (FDA) has approved phentolamine ophthalmic solution (RYZUMVI) 0.75% for the treatment of 

 produced by adrenergic agonists or parasympatholytic agents.

Announced by Ocuphire Pharma and Viatris Inc. on September 27, the ophthalmic solution is expected to become commercially available in the US in the first half of 2024.

“The FDA’s approval of RYZUMVI marks a significant milestone for our eye care division and underscores Viatris’ commitment to advancing eye care and enhancing access for both eye care professionals and patients,” said Jeffery Nau, PhD, eye care division president, Viatris.

Phentolamine ophthalmic solution 0.75% is a relatively non-selective alpha-1 and alpha-2 adrenergic agnostic. Phentolamine reversibly binds to receptors of the radial iris dilator muscle and reduces pupil diameter. It directly antagonizes the mydriatic effect of an α-1 adrenergic agonist and indirectly reverses mydriasis induced by muscarinic antagonist effects on the iris sphincter muscle.

The ophthalmic solution was evaluated in the MIRA clinical trial program including more than 600 patients in the MIRA-1 phase 2b trial, the MIRA-2 and MIRA-3 phase 3 pivotal trials, and the MIRA-4 phase 3 pediatric trial.

A total of 553 participants aged 12 to 80 years with mydriasis induced by the instillation of phenylephrine or tropicamide or a combination of hydroxyamphetamine hydrobromide and tropicamide were randomized in the MIRA-2 and MIRA-3 trials. Trial investigators administered 2 drops in the study eye or 1 drop in the fellow eye of phentolamine ophthalmic solution or placebo 1 hour after the instillation of the mydriatic agent.

Analyses revealed the percentage of participants with study eyes returning to ≤0.2mm from baseline pupil diameter was statistically significantly greater (

 <.01) at all time points measured from 60 minutes through 24 hours in the phentolamine ophthalmic solution group, compared with placebo, across both trials.

The efficacy of the phentolamine ophthalmic solution was similar for all age ranges, including pediatric subjects aged 3 to 17 years. Pediatric populations aged 12 to 17 years (n = 27) were treated in MIRA-2 and MIRA-3 trials and those aged 3 to 11 years (n = 11) were treated in MIRA-4.

Safety analyses showed the most common ocular adverse reactions reported in >5% of subjects were instillation site discomfort, including pain, stinging, and burning (16%) and conjunctival hyperemia (12%). It showed the only non-ocular adverse reactions reported in >5% of subjects were dysgeusia (6%).

An estimated 100 million comprehensive eye exams take place each year in the US that involve pharmacologically-induced mydriasis of the pupils, to examine the retina for routine check-ups, disease monitoring, or surgical procedures. Mydriasis can last up to 24 hours in adults and children. Side effects of the procedure can include photophobia and blurred vision, making it difficult for patients to read, work, and drive.

“Comprehensive dilated eye exams are vital for early detection of vision-compromising diseases,” Nau said. “Our hope is that by addressing patient dilation barriers, we’re empowering eye care professionals to broaden exam availability, leading to enhanced eye health outcomes.”

Ocuphire Pharma and Viatris announce FDA approval of RYZUMVITM (Phentolamine Ophthalmic Solution) 0.75% eye drops for the treatment of pharmacologically-induced mydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) agents. Ocuphire Pharma, Inc. September 27, 2023. Accessed September 27, 2023. https://www.ocuphire.com/news-media/press-releases/detail/415/ocuphire-pharma-and-viatris-announce-fda-approval-of.

Iapoce C. FDA accepts New Drug Application for NYXOL for reversal of Mydriasis. HCP Live. February 21, 2023. Accessed September 27, 2023. https://www.hcplive.com/view/fda-accepts-nda-nyxol-reversal-mydriasis.

According to the approval, the percentage of study eyes returning to ≤0.2 mm from baseline pupil diameter was statistically significantly greater in the phentolamine ophthalmic solution group than placebo. 

FDA Approves Phentolamine Ophthalmic Solution for Pharmacologically-Induced Mydriasis

Credit: Emory University School of Medicine

New findings from a retrospective cohort study of people with hepatitis C virus (HCV) suggest use of direct-acting antiviral (DAA) therapy was associated with sustained virologic response (SVR), regardless of alcohol consumption.

An analysis of nearly 70,000 patients, results of the study suggest 94.4% of patients with HCV achieved SVR regardless of alcohol use, with this association with SVR present among those with high-risk consumption or alcohol use disorder.

“With the advent of safe and highly effective direct-acting antiviral therapy for HCV, the impact of alcohol use on achieving SVR is less clear,” wrote investigators.

Globally, the World Health Organization estimates 58 million people have chronic HCV infection, with about 1.5 million new infections occurring every year. DAAs can cure more than 95% of people with HCV.

 HCV cure is confirmed when HCV RNA remains undetectable at 12 weeks after the end of treatment, known as SVR.

To assess the impact of alcohol use at DAA treatment initiation on the likelihood of SVR, Emily Cartwright, MD, associate professor of medicine in the division of infectious diseases at Emory University School of Medicine, and a team of investigators collected electronic health records for patients who initiated DAA therapy between January 1, 2014 and June 30, 2018 from the US Department of Veterans Affairs. Of the 94,388 patients who initiated DAA therapy in this time frame, 14,057 had no information to define SVR in primary analyses and 7339 were missing data for body mass index, smoking status, fibrosis-4 score, or HCV genotype.

In total, 69,229 patients with a mean age of 62.6 (standard deviation [SD], 4.5) years were included in the primary analysis. Among the cohort, 67,150 (97.0%) participants were male; 34,655 (50.1%) were non-Hispanic White, 28,094 (40.6%) were non-Hispanic Black, and 58,477 (84.5%) had HCV genotype 1. At DAA initiation, 46,220 (66.8%) patients were current smokers and 35,032 (50.6%) had fibrosis 4 scores between 1.45 and 3.25.

The primary exposure variable combined information on alcohol consumption and alcohol use disorder diagnoses ascertained in the 18 months before the index date. Investigators generated alcohol use categories based on AUDIT-C scores and alcohol use disorder diagnoses, including abstinent without history of alcohol use disorder, abstinent with history of alcohol use disorder, lower-risk consumption, moderate-risk consumption, and high-risk consumption or alcohol use disorder.

The primary outcome of interest was SVR, which was defined as undetectable HVC RNA for 12 weeks or longer and less than 6 months after completion of DAA therapy. Investigators also considered covariates including age, sex, race, ethnicity, rural or urban residency type, body mass index, smoking status, HIV coinfection, Charlson Comorbidity Index score, liver-related variables, and other HCV treatment-related variables.

A total of 32,290 individuals (46.6%) were abstinent without alcohol use disorder, 9192 (13.3%) were abstinent with alcohol use disorder, 13,415 (19.4%) had lower-risk consumption, 3117 (4.5%) had moderate-risk consumption, and 11,215 (16.2%) had high-risk consumption or alcohol use disorder.

Among the cohort, 65,355 (94.4%) participants achieved SVR. In an unadjusted model, patients who were abstinent without alcohol use disorder history (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.81-0.97) and those who were abstinent with alcohol use disorder history (OR, 0.71; 95% CI, 0.64-0.80) had lower odds of achieving SVR compared to patients who reported lower-risk consumption. Upon adjustment, there was no evidence of a significant association between alcohol category and odds of SVR, even for patients with high-risk consumption or alcohol use disorder (OR, 0.95; 95% CI, 0.85-1.07). Investigators also pointed out the association of alcohol category with the odds of SVR did not differ between participants with baseline stage of hepatic fibrosis ≤ 3.25 compared to > 3.25 (

Findings persisted after investigators included patients with missing data using multiple imputation (lowest adjusted OR, 0.90; 95% CI, 0.80-1.02 for patients who were abstinent with alcohol use disorder history) and assuming all patients with missing outcome data achieved SVR (lowest adjusted OR, 0.94; 95% CI, 0.84-1.06 for patients who were abstinent with alcohol use disorder history).

“Our findings suggest that DAA therapy should be provided and reimbursed despite alcohol consumption or history of AUD. Restricting access to DAA therapy according to alcohol consumption or AUD creates an unnecessary barrier to patients accessing DAA therapy and challenges HCV elimination goals,” investigators concluded.

Cartwright EJ, Pierret C, Minassian C, et al. Alcohol Use and Sustained Virologic Response to Hepatitis C Virus Direct-Acting Antiviral Therapy. 

Nearly 95% of patients with HCV treated with DAA therapy achieved SVR, regardless of alcohol consumption.

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