How can we manage the safety concerns associated with the increase in biologics for psoriasis?

Silfvast‐Kaiser, Annika; Menter, M. Alan

doi:10.1080/14740338.2020.1718102

Cited by 3 publications

(5 citation statements)

References 15 publications

(28 reference statements)

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“…With regard to the infection types, we found that URIs and nasopharyngitis were the most commonly mentioned infectious adverse events, which is compatible with previous reviews. 73 Other than the relatively non-serious infections, reactivation of TB has raised significant concern in endemic areas such as Asia, and screening for TB before initiation of TNFi therapy was routinely performed in studies after 2008. If latent TB was confirmed, patients were required to take prophylactic drugs.…”

Section: Discussionmentioning

confidence: 99%

Infection risk in psoriatic patients receiving tumour necrosis factor inhibitors: a 20‐year systematic review and meta‐analysis of randomized controlled trials

Lin

et al. 2022

Acad Dermatol Venereol

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Tumour necrosis factor inhibitors (TNFis) are commonly used for treating psoriatic diseases; however, the risk of infection while receiving TNFis remains uncertain. The aim of this study was to investigate the infection risk in patients with psoriatic disease receiving TNFis. A prospectively registered systematic literature search was conducted in Medline (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and the http://clinicaltrials.gov databases from inception to December 31, 2021. We included double‐blind randomized controlled trials that compared TNFis or other biologics with placebo in adults with psoriasis or psoriatic arthritis. The primary outcomes included overall and serious infection risks, and secondary outcomes included upper respiratory infections and nasopharyngitis risks. The risk ratio of the dichotomous outcome was calculated using the Mantel–Haenszel method with random effects, and heterogeneity was assessed using Cochran's Q statistic and quantified using the I‐squared statistic. A total of 48 studies with 15 464 patients with psoriatic diseases were included. The meta‐analysis demonstrated a slightly increased overall infection risk (risk ratio = 1.09; 95% confidence interval, 1.02–1.15) but not serious infection risk (risk ratio = 0.95; 95% confidence interval, 0.61–1.49) among patients receiving TNFis. There were also no increased risks of upper respiratory infections (risk ratio = 1.10; 95% confidence interval, 0.94–1.28) or nasopharyngitis (risk ratio = 1.14; 95% confidence interval, 1.00–1.30). In subgroup analyses using the fixed effects model, only etanercept and certolizumab pegol were, respectively, associated with an increased risk of overall infection (RR = 1.14, 95% CI, 1.03–1.27) and upper respiratory infections (RR = 1.42, 95% CI, 1.02–1.98). In conclusion, evidence to date suggests an increased overall infection risk that is generally tolerable in patients with psoriatic diseases receiving TNFis. There are no increased risks of serious infections, upper respiratory infections or nasopharyngitis.

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Section: Discussionmentioning

confidence: 99%

Infection risk in psoriatic patients receiving tumour necrosis factor inhibitors: a 20‐year systematic review and meta‐analysis of randomized controlled trials

Lin

et al. 2022

Acad Dermatol Venereol

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“…Neutralization or blockade of IL‐17 secretion by biologics has demonstrated robust efficacy 12 ; however, no clinical response within the initial treatment timeframe, loss of drug effectiveness after initial remission, and the length of time until discontinuation of a drug remains a challenge for these biologics 13,14 . Furthermore, patient adherence, accessibility, and reluctance due to concern about potential side effects of biologics prevent systemic treatment, leaving patients undertreated 15,16 . Thus, there remains an unmet need for therapeutic intervention of the Th17 cell lineage with an orally bioavailable, small molecule medication.…”

Section: Introductionmentioning

confidence: 99%

“… 13 , 14 Furthermore, patient adherence, accessibility, and reluctance due to concern about potential side effects of biologics prevent systemic treatment, leaving patients undertreated. 15 , 16 Thus, there remains an unmet need for therapeutic intervention of the Th17 cell lineage with an orally bioavailable, small molecule medication.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, safety, and efficacy of cedirogant from phase I studies in healthy participants and patients with chronic plaque psoriasis

Mohamed,

Qian,

D'Cunha

et al. 2023

Clinical Translational Sci

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Cedirogant is an inverse agonist of retinoic acid‐related orphan receptor gamma thymus (RORγt) developed for the treatment of moderate to severe chronic plaque psoriasis. Here, we report the results from two phase I studies in which the pharmacokinetics (PK), safety, and efficacy of cedirogant in healthy participants and patients with moderate to severe chronic plaque psoriasis were evaluated. The studies consisted of single (20–750 mg) and multiple (75–375 mg once‐daily [q.d.]) ascending dose designs, with effect of food and itraconazole on cedirogant exposure also evaluated. Safety and PK were evaluated for both healthy participants and psoriasis patients, and efficacy was assessed in psoriasis patients. Following single and multiple doses, cedirogant mean terminal half‐life ranged from 16 to 28 h and median time to reach maximum plasma concentration ranged from 2 to 5 h across both populations. Cedirogant plasma exposures were dose‐proportional after single doses and less than dose‐proportional from 75 to 375 mg q.d. doses. Steady‐state concentrations were achieved within 12 days. Accumulation ratios ranged from approximately 1.2 to 1.8 across tested doses. Food had minimal effect and itraconazole had limited impact on cedirogant exposure. No discontinuations or serious adverse events due to cedirogant were recorded. Psoriasis Area and Severity Index (PASI) and Self‐Assessment of Psoriasis Symptoms (SAPS) assessments demonstrated numerical improvement with treatment of cedirogant 375 mg q.d. compared with placebo. The PK, safety, and efficacy profiles of cedirogant supported advancing it to phase II clinical trial in psoriasis patients.

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“…In general, biologics are well tolerated with limited AEs and no cumulative organ toxicity. [11][12][13][14] However, available data on the safety of biologics are mainly based on randomized controlled trials with limited follow-up time and highly selective patient populations. These do not reflect the real-world setting, resulting in limited long-term safety data and differences in the incidence of AEs compared with real-world registries.…”

Section: Introductionmentioning

confidence: 99%

“…Therapeutic management of psoriasis has changed dramatically with the introduction of biologics targeting specific immune mediators, divided into four main groups: anti‐TNFα, anti‐IL‐12/23, anti‐IL‐17 and anti‐IL‐23. In general, biologics are well tolerated with limited AEs and no cumulative organ toxicity 11–14 . However, available data on the safety of biologics are mainly based on randomized controlled trials with limited follow‐up time and highly selective patient populations.…”

Section: Introductionmentioning

confidence: 99%

Sex differences in adverse events from systemic treatments for psoriasis: A decade of insights from the Swiss Psoriasis Registry (SDNTT)

Verardi,

Maul,

Borsky

et al. 2023

Acad Dermatol Venereol

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BackgroundPsoriasis is a disease that often requires prolonged systemic treatment. It is important to determine the safety of available therapies. There is currently little insight into sex‐specific differences in the safety of systemic psoriasis therapies.ObjectivesTo examine the real‐world, long‐term safety of systemic psoriasis therapies with sex stratification in drug‐related adverse events (ADRs).MethodsTen‐year data from adults with moderate‐to‐severe psoriasis requiring systemic treatment (conventional systemic therapies [CST], biologics) were obtained from the Swiss psoriasis registry (SDNTT). ADRs were categorized according to the international terminology Medical Dictionary for Regulatory Activities (MedDRA). Safety was assessed by calculating event rates per 100 patient‐years (PY). We used descriptive statistics for patient and disease characteristics, and binomial and t‐tests to compare treatment groups and sex.ResultsIn total, 791 patients (290 females) were included with a mean age of 46 years. 358 (45%) received CSTs and 433 (55%) biologics; both groups had similar baseline characteristics except for more joint involvement in patients using biologics (26.86% vs. 14.8%, p < 0.0001). CSTs were associated with a 2.2‐fold higher ADR rate (40.43/100 PY vs. 18.22/100 PY, p < 0.0001) and an 8.0‐fold higher drug‐related discontinuation rate than biologics (0.16/PY vs. 0.02/PY, p < 0.0001). Trends showed non‐significant higher serious adverse event rates per 100 PY for biologics (8.19, CI 6.87–9.68) compared to CSTs (7.08, CI 5.39–9.13) (p = 0.3922). Sex stratification revealed a significantly higher overall ADR rate for all treatments in females (1.8‐fold for CSTs [57.30/100 PY vs. 31.69/100 PY] and 2.0‐fold for biologics [27.36/100 PY vs. 13.9/100 PY], p < 0.0001), and drug‐related discontinuation rates for most CSTs in females.ConclusionFemales were associated with a significantly higher rate of ADRs and drug‐related discontinuation rates. Sex stratification should be taken into consideration when designing studies in the patient‐tailored management of psoriasis.

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How can we manage the safety concerns associated with the increase in biologics for psoriasis?

Cited by 3 publications

References 15 publications

Infection risk in psoriatic patients receiving tumour necrosis factor inhibitors: a 20‐year systematic review and meta‐analysis of randomized controlled trials

Infection risk in psoriatic patients receiving tumour necrosis factor inhibitors: a 20‐year systematic review and meta‐analysis of randomized controlled trials

Pharmacokinetics, safety, and efficacy of cedirogant from phase I studies in healthy participants and patients with chronic plaque psoriasis

Sex differences in adverse events from systemic treatments for psoriasis: A decade of insights from the Swiss Psoriasis Registry (SDNTT)

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