Daily Archives: April 18, 2024

Guselkumab demonstrates significant improvements in psoriasis symptoms and health-related quality of life (HRQoL), according to week 28 results of the German G-EPOSS study published in the Journal of the European Academy of Dermatology and Venereology. The study also found that guselkumab reduced sexual impairment and perceived stigmatization in participants.1

Researchers Gerdes et al sought to evaluate the efficacy and safety of guselkumab, particularly in the above disease-specific and social domains. It is well-documented that the burden of psoriasis extends beyond physical symptoms, significantly impacting patients' quality of life, leading to psychological distress and social stigma.2

Furthermore, sexual impairment and stigmatization are significant yet often overlooked dimensions of psoriasis-related morbidity. Patients with psoriasis, especially those with genital involvement, are at increased risk of sexual dysfunction and stigmatization.3 In fact, the World Health Organization lists sexual impairment and perceived stigmatization as key components of its comprehensive psoriasis action plan.4

"Stigmatization affects 73%99% of patients with psoriasis and can result in social exclusion, depression, fear of loss of employment and embarrassment, and can impact on relationships/family planning," according to the study's authors.

Researchers conducted the G-EPOSS study, a prospective, non-interventional, multicenter study. Patients with moderate-to-severe plaque psoriasis were enrolled in the study between October 2019 and August 2021 across 44 study sites in Germany.

Participants were required to be 18 years of age and older with a plaque psoriasis diagnosis of moderate-to-severe nature as determined by a baseline Psoriasis Area and Severity Index (PASI) score of greater than 3 and were candidates for systemic therapy. Prospective patients were also required to be candidates for systemic therapy. Apart from biologic therapies, any individuals taking concomitant medications for their psoriasis were permitted to maintain usage of these medications.

All patients received 100 mg of guselkumab at weeks 0, 4, and every 8 weeks afterwards through a total duration of 76 weeks.

In total, 304 patients were part of the safety analysis, having received at least one dose of guselkumab, with 293 included in the evaluable set population. Patients were excluded from the evaluable set population if they lacked post-baseline PASI measurements or deviated significantly from the observational plan. Data was available for different time points: 282 patients at week 12, 252 at week 20, and 265 at week 28. Patient withdrawals before week 28 were minimal, with 6 (2.0%) attributed to adverse events.

Baseline characteristics, such as age, gender distribution, weight, BMI, and disease duration, were recorded. Prior treatment history indicated that a significant proportion of patients had received systemic (58.0%) or biologic (25.9%) therapy before participating in the study.

"Stigmatization affects 73%99% of patients with psoriasis and can result in social exclusion, depression, fear of loss of employment and embarrassment, and can impact on relationships/family planning."

The study demonstrated significant improvements in psoriasis severity and related symptoms with guselkumab treatment. A substantial percentage of patients achieved primary endpoints of PASI3 (83.0%), PASI1 (56.2%), and PASI=0 (35.1%) by week 28. Nail disease and anogenital psoriasis also showed considerable improvements.

Patient-reported outcomes, particularly Dermatology Life Quality Index (DLQI) and Relationship and Sexuality Scale (RSS), indicated enhanced quality of life and sexual satisfaction. DLQI scores improved, with a majority achieving DLQI 01 at W28. RSS responses showed decreased sexual impairment and fear of sexual intercourse, with an increase in satisfaction with sexual frequency.

Perceived stigmatization, as assessed by the Perceived Stigmatization Questionnaire, decreased over time, indicating reduced social discomfort associated with psoriasis.

Safety outcomes showed that adverse events were generally mild, with infections, skin disorders, and musculoskeletal issues being the most common. Drug-related adverse events were infrequent, with no drug-related serious adverse events or withdrawals due to such events.

"The PRO results demonstrate the clinical relevance of Q9 of the commonly used DLQI as a sentinel to trigger further investigations into sexual difficulties or anogenital skin involvement," wrote Gerdes et al. "Such a holistic approach to patient care may not only positively impact the patient's sense of self-esteem but also the patient's overall degree of social engagement and participation. Further results from the final W76 analysis of G-EPOSS will follow and provide further insights."

References

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Guselkumab Demonstrates Significant Improvement in Psoriasis Symptoms and HRQoL, Reduces Sexual Impairment ... - Dermatology Times

Individuals with psoriasis with unexplained arthralgia and non-inflammatory symptoms are at a far greater risk of psoriatic arthritis (PsA) development, according to new findings, providing new information on subclinical PsA.1

These findings resulted from new research conducted due to the lack of real-world data on subclinical PsA, which is described as the existence of arthralgia in psoriasis patients. This was considered invaluable given the noted higher risk of PsA among those with subclinical PsA.

The new analysis was led by Alen Zabotti, from the department of medical and biological sciences at the University Hospital Santa Maria della Misericordia Rheumatology Clinic in Udine, Italy. Zabotti et al. acknowledged that a prior systematic literature review had indicated the lack of data on the transition between psoriasis to PsA.2

These could help to better define outcomes for PsA prevention studies in the context of prevention/interception of PsA and early diagnosis, Zabotti and colleagues wrote. Therefore, this study investigated the subclinical stage of PsA in terms of risk of progression and clinical symptoms, and to describe the clinical features of new-onset PsA in (psoriasis) cases.3

The investigators assessed data drawn from 2 ongoing European prospective cohorts of individuals with psoriasis, looking at both the Italian cohort, RAPSODI (Ultrasonographic Risk Factors to Develop Psoriatic Arthritis in Psoriatic Patients with and Without ClinIcal Arthralgia), and the German PACE cohort (Psoriasis and Psoriatic Arthritis Cohort Erlangen), both of which were longitudinal studies.1

Subjects featured within the 2 cohorts had been given a diangosis with definite psoriasis of the skin or nails by dermatologists. They were also enriched for PsA risk, with many having arthralgia suggesting a potential risk of PsA development.

The investigators looked at study participants that did not have clinical PsA by the time of their entry to the cohort and those with no visible swelling of joints. Subjects with a history of enthesitis, synovitis, dactylitis, or inflammatory back pain were not included in the research, and those who were included were reassessed every half year, being told by the team to report inflammatory symptoms to their designated rheumatologists.

In the period between January 2017 - December 2022, there had been 215 Italian participants enrolled in RAPSODI with psoriasis, of which 66.0% were shown to have baseline arthralgia indicating the presence of subclinical PsA. Within those in the PACE cohort, 169 participants in total between January 2011 - July 2018, all were determined to have subclinical PsA.

The investigators diagnosed new-onset clinical PsA at the time of follow-up through the use of experienced rheumatologists and with CASPAR criteria fulfillment. The team would also characterize the manifestations of subjects new-onset clinical PsA by enthesitis, dactylitis, peripheral arthritis, and axial involvement.

Additionally, the team recorded participants clinical features at the time of PsA diagnosis, some of which included enthesitis index, joint counts, and presence of dactylitis.

There were 384 individuals given a diagnosis of psoriasis who took part in the study, as well as an average follow-up duration of 33.0 months. Additionally, 80.9% of these individuals were shown to have subclinical PsA, indicating there had been an incidence rate of PsA of 7.7 per 100 patient-years.

The investigators reported that their subclinical PsA patients had a significantly higher risk of developing PsA as opposed to subjects that had psoriasis exclusively (HR=11.7, 95% CI 1.57 to 86.7, P = .016). The research team noted that the cumulative incidence function (CIF) estimated the probability of new-onset PsA was about 9.4% (95% CI 4.7% - 10.6%) by the 12-month mark and that it was 22.7% (95% CI 17.2% - 28.6%) by the 36-month mark.

A notable finding was that 58.9% of subjects had been shown to have inflammatory symptoms during the months immediately preceding their diagnosis of PsA, but 83.9% were found to have non-inflammatory symptoms before their PsA diagnosis. Additionally, the most frequent pattern of presentation was shown to be peripheral joint swelling for 82.1% of those with PsA.

We have confirmed that patients with (psoriasis) experiencing unexplained arthralgia, also reporting non-inflammatory symptoms, are at a significantly elevated risk of developing PsA, they wrote. Additionally, peripheral arthritis, mainly oligoarthritis, is the most common PsA presentation in cohorts with PsO enriched for arthralgia.

References

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Psoriasis Patients with Arthralgia At Increased Risk of Psoriatic Arthritis Development - MD Magazine

Alan J. Kivitz, MD

Credit: Altoona Arthritis and Osteoporosis Center

A new study found certain doses of secukinumab had greater odds of alleviating psoriatic arthritis (PsA) symptoms than placebo.1

In general, US patients treated with secukinumab 300 mg and secukinumab 150 mg with loading dose achieved the highest response rates, including ACR50 and ACR70 responses and the proportions of patients showing at least an MCID improvement in the health-related quality-of-life measure HAQ-DI, wrote investigators, led by Alan J. Kivitz, MD, from the Altoona Center for Clinical Research/Altoona Arthritis and Osteoporosis Center.

PsA is linked to reduced quality of life, physical function, and work productivity. Five FUTURE studies have shown secukinumab, a selective inhibitor of interleukin 17A, provides rapid and significant improvement in the symptoms of PsA and has a favorable safety profile.2

Investigators aimed to compare secukinumab and placebo in challenging-to-treat US patients with PsA.1 They pooled data from patients enrolled in phase 3 FUTURE 2 5 studies, excluding FUTURE 1 due to the study including an intravenous loading dose that is not approved by the US Food and Drug Administration (FDA) or the European Commission (EC) for PsA.

The FUTURE 2 5 trials randomized US patients who were in the minority of the total population with a harder-to-treat disease. This means patients may have had a greater body weight, greater tender and swollen joint counts, and a greater likelihood of enthesitis, dactylitis, and prior exposure to tumor necrosis factor inhibitors (TNFi). Patients either received secukinumab 300 or 150 mg with or without a subcutaneous loading dose or placebo.

The team assessed efficacy, health-related quality of life, and safety at week 16. Subgroup analyses examined TNFi status and body mass index (BMI). With logistic regression, they estimated odds ratios for the American College of Rheumatology (ACR) 20/50/70 and Psoriasis Area and Severity Index (PASI) 75/90/100 responses by treatment.

Although 2147 patients were originally randomized, the current pooled analysis only included 279 patients with 55.6% women. Participants had a mean BMI of > 30 kg/m2 and 55.2% had prior TNFi treatment.

Overall, at week 16, patients on secukinumab 300 mg (59.7%; P < .0001) and secukinumab 150 mg with loading dose (43.4%; P < .0001) had significantly greater ACR20 response rates. Patients on secukinumab 150 mg without a loader dose had greater response rates than placebo but was non-significant (32.5%; P = .30).

When evaluating the PASI score at week 16, patients had greater response rates on secukinumab than on placebo, with more improvements on secukinumab 300 mg than secukinumab 150 mg. Compared to placebo (9.1%), more patients on secukinumab had improved nail disease, with mNAPSI75 rates of 36.4, 24.6, and 15% for secukinumab 300, 150, and 150 mg without loading dose, respectively. Patients also had more improvements in health-related quality of life at week 16 when on secukinumab.

Patients responded to secukinumab as early as week 4, and ACR50 and ACR70 responses were greater with any secukinumab dose than placebo. More patients on secukinumab than placebo had a 100% reduction in PsA symptoms.

When evaluating the odds ratio, the findings revealed patients receiving secukinumab 300 mg and 150 mg with loading dose had greater odds of responding to at least 20%, 50%, or 70% of the treatment in tender and swollen joints (ACR 20/50/70) (P < .05) than patients on placebo. This indicates patients on secukinumab 300 mg and 150 mg with loading doses have the greatest clinical response rates. In contrast, Patients on secukinumab 150 mg without loading dose did not have better odds than placebo.

Patients on all doses of secukinumab had greater odds of a 75% greater reduction in PASI scores from baseline (PASI75) compared to placebo (P < .05). As for a 90% of 100% improvement from baseline on the PSAI score (PASI90 and PASI100), only the secukinumab 300 mg group worked significantly better compared to placebo (P < .05).

Secukinumab was also demonstrated to be as safe as placebo, with the frequency of all treatment-emergent adverse events similar for patients receiving secukinumab 300 mg (51.4%), secukinumab 150 mg with loading dose (54.2%), secukinumab 150 mg without loading dose (55.9%), and placebo (64.4%). The most common adverse events were upper respiratory tract infection, nasopharyngitis, nausea, and sinusitis.

Overall, secukinumab brought rapid improvements in disease activity and quality of life. The results suggest secukinumab 300 mg better improves symptoms of PsA and active psoriasis than secukinumab 150 mg.

The team underlined many limitations, including not adjusting for logistic regression analyses, nominal P values were calculated for hypothesis generation, patients were not stratified based on weight or BMI at randomization, radiographic progression data was only available from FUTURE 5, and patients in all groups had variability in vdH-mTSS scores from baseline to week 24.

This analysis also suggests that a loading-dose regimenparticularly for patients receiving secukinumab 150 mgincreases the odds of optimal outcomes in US patients with PsA treated with secukinumab, investigators concluded.

References

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Secukinumab 300 mg May Improve PsA or Active Psoriasis More Than 150 mg - MD Magazine

Laura C. Coates, MBChB, MRCP, PhD

Credit: X (Twitter)

Guselkumab treatment led to early and durable improvements in key Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-recognized areas In biologic-nave psoriatic arthritis (PsA) patients through 2 years, according to new findings.1

These findings represented the conclusion of a new post-hoc analysis of the phase 3, double-blind, randomized, placebo-controlled trial assessing treatment of PsA with guselkumab among adults with active disease. The phase 3 analysis had been carried out in the period between July 2017 - November 2020.

This new post-hoc analysis was led by Laura C. Coates, MBChB, MRCP, PhD, from the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences at University of Oxford in the UK. Coates and colleagues noted the 6 GRAPPA disease domains, adding that the GRAPPA guidelines urge achievement of the lowest possible disease activity level across all domains.2

Informed by the GRAPPA treatment goal of achieving the lowest possible level of disease activity in all affected disease domainsthe objective of the present post hoc analysis was to evaluate the long-term (Week 100) effectiveness of guselkumab across GRAPPA-identified PsA domains and related conditions assessed in DISCOVER-2, Coates and colleagues wrote.

As mentioned previously, the research team carried out their post-hoc analyses of the phase 3 data drawn from the DISCOVER-2 study, a trial which had been aimed at subjects who had been biologic or Janus kinase inhibitor-nave and active PsA. Active disease had been defined as maintaining 5 swollen joints minimum as well as 5 tender joints at least and a C-reactive protein level of 0.6 mg/dL or more.

Study subjects were randomized using a 1:1:1 ratio, being treated with either guselkumab every 4 weeks (Q4W) or the same treatment every 8 weeks (Q8W). The alternative was receiving a placebo with crossover to guselkumab in the subsequent period.

The investigators looked at several different domains highlighted by GRAPPA, which included peripheral arthritis, overall disease activity, enthesitis/dactylitis, axial disease, and skin psoriasis. Additionally, the research team assessed PsA-connected issues including uveitis and inflammatory bowel disease (IBD), evaluated through adverse events (AEs) reported up to the 112-week mark.

The team looked at post-baseline changes through the 100-week mark in continuous outcomes, implementing repeated measures mixed-effects models as well as adjusting for patients scores at baseline. Rates of response rates in binary measures were identified by the investigators through the use of non-responder imputation methods.

The research team reported that 90% of the subjects who had been randomized to be treated with guselkumab finished up the process by the 100-week point. Following an initial disease activity decrease with the drug, the team identified sustained signs of success over several of the aforementioned domains of PsA up to Week 100.

The investigators found that the participants rates of reaching their therapeutic targets showed signs of increasing through the 100-week mark with the drug administered to subjects Q4W or every 8 weeks (Q8W). These signs of improvement included low disease activity (LDA) achievement according to the Disease Activity Index for PsA being 62% with Q4W and 59% after Q8W.

The research team also noted enthesitis rates of resolution being 61% and 70% following Q4W and Q8W, respectively, and dactylitis resolution rates being 72% and 83% with Q4W and Q8W, respectively. Furthermore, the team found subjects with 100% improvement in their Psoriasis Area and Severity Index scores (PASI 100) were 59% and 53% with Q4W and Q8W, respectively.

Lastly, those reporting LDA according to the Psoriatic Arthritis Disease Activity Score were 51% and 49% with Q8W and Q4W, respectively, as well as minimal disease activity achievement among 38% and 40% with Q4W with Q8W, respectively.

The investigators found no instances up to the 112-week point of IBD among subjects who had been given guselkumab. Additionally, only a single case of uveitis was observed.

No exacerbations or new onset of IBD were reported, with a single occurrence of uveitis observed through Week 100 in guselkumab-treated patients, aligning with the established safety profile of guselkumab, they wrote.

References

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Guselkumab Led to Improvements Over Several Psoriatic Arthritis Disease Domains - MD Magazine