Psoriasis Review

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biologic

Risk of Malignancy Comparable Between Biologics 

A recent poster study, presented at the 2018 Fall Clinical Dermatology Conference, found similar rates of malignancy between brodalumab (Siliq), an IL-17A inhibitor, and ustekinumab (Stelara), an IL-12 and IL-23 inhibitor, among participants with plaque psoriasis.

“Although the role of the IL-17 pathway in malignancy risk is not well characterized, potential malignancies are considered an event of interest with immunomodulatory biologics,” the researchers stated.

In the study, the researchers analyzed data pooled from phase 2 trials, and 3 large, randomized, phase 3 trials that compared the efficacy of brodalumab, ustekinumab, and placebo among participants with moderate to severe plaque psoriasis. They assessed all adverse events that were reported as neoplasms benign, malignant, and unspecified (including cysts and polyps), and classified confirmed events as adjudicated malignancies. Exposure- or time-adjusted event rates for malignancies were determined per 100 patient-years using data from the 12-week, 52-week, and long-term pools.

During the 12-week period, few malignancies were reported, with 2 among participants who received ustekinumab and 4 among those who received brodalumab. The researchers found that the exposure-adjusted malignancy event rate through week 52 was lower among participants who received brodalumab compared with those who received ustekinumab, with the majority of malignancies reported as grade 2 or less. In addition, the ratio of basal cell carcinoma to squamous cell carcinoma was 3:8:1 for the brodalumab groups compared with 4:1 for the ustekinumab group. Rates of malignancies from analyses of the long-term data were consistent with the findings from the 52-week period.

Two participants in the brodalumab groups experienced grade 4 serious malignancy adverse events (bile duct adenocarcinoma and follicle center lymphoma), and 1 participant in the ustekinumab group died from pancreatic carcinoma.

“In clinical studies of brodalumab, rates of malignancy were generally low compared to those previously reported for IL-17A inhibitors secukinumab (Cosentyx) and ixekizumab (Taltz). There was no increased risk of malignancy with brodalumab relative to ustekinumab through 52 weeks” the researchers concluded. “Longer follow up time is needed to fully characterize the risk of malignancy with brodalumab.” 

Reference

Lebwohl M, Gordon K, Green L, et al. Malignancy rates in the brodalumab psoriasis clinical studies. Presented at: 2018 Fall Clinical Dermatology Conference; October 18-21, 2018; Las Vegas, NV.

IBD

Study Shows Link Between Psoriasis and IBD 

Psoriasis was associated with an increased risk for inflammatory bowel disease (IBD), according to the findings of a recent study.

“Patients with psoriasis may experience comorbidities involving cardiovascular diseases, chronic kidney disease, uveitis, psychiatric disturbances, and metabolic syndrome,” the researchers stated. “However, the association between psoriasis and IBD has been largely unclear.”

In the systematic review, the researchers identified 9 studies that assessed the odds or risk of IBD among a total of 7,794,087 participants with psoriasis using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. They analyzed the relative risk (RR) and odds ratio (OR) of IBD, Crohn disease, and ulcerative colitis, separately, and conducted a subgroup analysis on these risks among those with psoriatic arthritis.

The researchers observed significant associations between psoriasis and Crohn disease (OR, 1.70; 95% CI, 1.20-2.40) and ulcerative colitis (OR, 1.75; 95% CI, 1.49-2.05). In addition, psoriasis was associated with an increased risk for Crohn disease (RR, 2.53; 95% CI, 1.65-3.89) and ulcerative colitis (RR, 1.71; 95% CI, 1.55-1.89).

“These findings suggest that psoriasis is significantly associated with IBD,” the researchers concluded. “Gastroenterology consultation may be indicated when patients with psoriasis present with bowel symptoms.” 

Reference

Fu  Y, Lee C, Chi C. Association of psoriasis with inflammatory bowel disease: A systematic review and meta-analysis [published online October 24, 2018]. JAMA Dermatol. doi:10.1001/jamadermatol.2018.3631

scalp psoriasis

Treating Early Subclinical Inflammation Could Prevent PsA 

Early treatment was associated with regression of subclinical inflammation among patients with psoriasis without psoriatic arthritis (PsA), according to the findings of a recent study.

“Our findings support the concept that therapies that suppress subclinical enthesopathy may have the potential to prevent arthritis development, at least in a subset of cases, but this needs formal testing in longitudinal studies,” the researchers stated. 

The open-label pilot study included 73 systemic therapy-naïve participants with moderate to severe psoriasis without symptoms of PsA and 23 healthy volunteers. All participants were screened using ultrasound for subclinical enthesitis at baseline. Twenty-three participants with inflammatory changes on ultrasound were treated with ustekinumab (Stelara) for 52 weeks.

At baseline and weeks 12, 24, and 52, the evolution of sonographic abnormalities was assessed using an extensive grey scale and power Doppler ultrasound protocol of the upper and lower limb entheses.

Overall, 49.3% of participants with psoriasis had at least 1 inflammatory entheseal abnormality on ultrasound. This confirms that subclinical enthesopathy among patients with psoriasis is not uncommon, the researchers wrote.

After treatment, the mean inflammation scores among participants with psoriasis were significantly reduced by 42.2% from baseline to week 24 and by 47.5% at week 52. However, entheseal structural abnormalities did not change significantly during treatment.

“IL-12/23 inhibition for psoriasis appears to suppress subclinical enthesopathy within 12 weeks of treatment, maintained to week 52,” the researchers concluded. 

Reference

Savage L, Goodfield M, Horton L, et al. Regression of peripheral subclinical enthesopathy in therapy-naïve patients treated with ustekinumab for moderate-to-severe chronic plaque psoriasis [published online November 22, 2018]. Arthritis Rheumatol. doi:10.1002/art.40778

depression

Impact of Depression on Treatment Outcomes 

Depression could be a predictor for poorer treatment outcomes, according to the findings of a recent study.1 

Patients with psoriasis are known to have higher rates of psychiatric comorbidities, including depression and anxiety.2 To determine whether anxiety or depression could predict responses to treatment, the researchers conducted a prospective cohort study that included 85 participants with psoriasis receiving 6 months of treatment with etanercept (Enbrel). They assessed Psoriasis Area and Severity Index (PASI) scores at baseline and months 1, 3, and 6, and evaluated the corresponding PASI 75/90 responses at each visit. In addition, the researchers assessed depression and anxiety symptoms at baseline and months 1, 3, and 6 using the Hospital Anxiety and Depression Scale (HADS). 

The researchers found that depressive symptoms were associated with female gender, longer disease duration, and higher PASI scores. Anxiety was associated with female gender, larger psoriasis-affected body surface area, and higher PASI scores. 

Treatment with etanercept was associated with decreases in HADS-Depression and HADS-Anxiety scores at months 1, 3, and 6 compared with baseline scores. However, participants with depression at baseline had lower PASI 75 response rates at months 3 and 6, and lower PASI 90 response rates at month 6 compared with those without depression at baseline.

In addition, the researchers found that depression at baseline was an independent predictor for the lower likelihood of achieving PASI 75 and PASI 90 responses at month 6. However, anxiety symptoms at baseline were not associated with responses to treatment. 

“Depression symptoms at baseline independently predict a worse clinical response to etanercept treatment in psoriasis patients,” the researchers concluded. 

References

1. Jin W, Zhang S, Duan Y. Depression symptoms predict worse clinical response to etanercept treatment in psoriasis patients [published online November 8, 2018]. Dermatology. doi:10.1159/000492784

2. Amin M, Lee EB, Wu JJ. Clinical update on psoriasis comorbidities. The Dermatologist. 2018;26(4):22-31.