Dataset Information

Risk of common infections among individuals with psoriasis in Sweden: A nationwide cohort study comparing secukinumab to ustekinumab.

ABSTRACT:

Purpose

To determine risk of respiratory tract infections, urinary tract infections and candidiasis in secukinumab users compared to ustekinumab users among individuals with psoriasis in Sweden.

Methods

This was a Swedish population-based register-linked new-user cohort study on individuals with psoriasis and psoriasis arthritis treated with secukinumab (2015-2017) and ustekinumab (2009-2017). Ever-never exposure definition was used, that is, each individual's follow-up time was attributed to the drug they were first exposed to. Risk of severe respiratory and urinary tract infections and candidiasis (diagnosis codes from out-patient specialist visits and in-patient hospitalisations) and respiratory and urinary tract infections treated in primary care (proxied by dispensation of antibiotics) was determined by adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox regression. We also give crude incidence rates and rate ratios.

Results

In total, 1955 new users of secukinumab (n = 848) and ustekinumab (n = 1107) were identified. There was a slightly increased risk of respiratory and urinary tract infections treated in primary care among secukinumab users compared to ustekinumab users (HR: 1.22, 95% CI: 1.03-1.43). Non-significant differences in estimated risk of severe respiratory and urinary tract infections (HR: 0.96, 95% CI: 0.57-1.61) and candidiasis (HR: 1.80, 95% CI: 0.84-3.84) treated in the hospital setting were observed.

Conclusion

We observed a slightly increased risk of respiratory and urinary tract infections treated in primary care among secukinumab users compared to ustekinumab users. Larger studies with longer follow-up are needed to draw conclusions on relative safety.

SUBMITTER: Srinivas C

PROVIDER: S-EPMC7756328 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Risk of common infections among individuals with psoriasis in Sweden: A nationwide cohort study comparing secukinumab to ustekinumab.

Srinivas Chaitra C Odsbu Ingvild I Linder Marie M

Pharmacoepidemiology and drug safety 20200925 12

<h4>Purpose</h4>To determine risk of respiratory tract infections, urinary tract infections and candidiasis in secukinumab users compared to ustekinumab users among individuals with psoriasis in Sweden.<h4>Methods</h4>This was a Swedish population-based register-linked new-user cohort study on individuals with psoriasis and psoriasis arthritis treated with secukinumab (2015-2017) and ustekinumab (2009-2017). Ever-never exposure definition was used, that is, each individual's follow-up time was a ...[more]

PMID: 32975344

Similar Datasets

Project description:IntroductionSecukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated superior efficacy to ustekinumab in the phase 3b CLEAR study of moderate to severe plaque psoriasis. Here, we report 16-week results from CLARITY, a second head-to-head trial comparing secukinumab with ustekinumab.MethodsIn the phase 3b CLARITY study, patients were randomized 1:1 to receive subcutaneous secukinumab 300 mg or ustekinumab per label. The co-primary objectives were to demonstrate the superiority of secukinumab over ustekinumab at Week 12 in relation to the proportion of patients with (1) 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI 90) and (2) a score of 0/1 (clear/almost clear) on the modified Investigator's Global Assessment (IGA mod 2011 0/1). Key secondary objectives were also assessed, as was Dermatology Life Quality Index (DLQI) 0/1 (no impact of skin disease on patients' quality of life) response. Missing values were handled by multiple imputation except for DLQI 0/1, where last observation carried forward techniques were utilized.ResultsBoth co-primary objectives were met: secukinumab was superior to ustekinumab for the proportion of patients achieving a PASI 90 (66.5% vs. 47.9%) and IGA mod 2011 0/1 response (72.3% vs. 55.4%) at Week 12 (p < 0.0001). PASI 90 responses were greater with secukinumab compared to ustekinumab from as early as Week 4 (16.7% vs. 4.0%) and out to Week 16 (76.6% vs. 54.2%). Similarly, IGA mod 2011 0/1 findings were greater with secukinumab at Week 4 (26.9% vs. 7.8%) and at Week 16 (78.6% vs. 59.1%). DLQI 0/1 response rates were also greater with secukinumab compared to ustekinumab at Week 4 (33.9% vs. 18.0%), Week 12 (64.0% vs. 51.7%), and Week 16 (68.4% vs. 55.9%).ConclusionThe results of this study confirm the superior efficacy of secukinumab over ustekinumab in treating patients with moderate to severe psoriasis.Trial registrationClinicaltrials.gov Identifier, NCT02826603.FundingNovartis Pharma AG, Basel, Switzerland.

Project description:ImportanceTreatments for psoriasis may be less effective in everyday practice than in clinical trials. Emulating a target trial using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) can provide treatment effect estimates that are robust and can inform both clinicians and regulatory bodies.ObjectivesTo assess the comparative effectiveness of ustekinumab and secukinumab in patients with psoriasis, and to test whether the relative effectiveness estimate of the CLEAR trial, a randomized clinical trial that compared secukinumab with ustekinumab for psoriasis, can be replicated.Design, setting, and participantsThis comparative effectiveness research study used a target trial emulation approach and was performed between November 2007 and August 2019. Data were obtained from BADBIR, a multicenter longitudinal pharmacovigilance register of patients with moderate to severe psoriasis in the United Kingdom and Republic of Ireland. Participants had chronic plaque psoriasis, were 18 years or older, and had at least 1 record of a Psoriasis Area and Severity Index (PASI) of 12 or higher before their initiation to secukinumab or ustekinumab. Propensity score (PS) 1:1 matched analysis and inverse probability treatment weighted analysis were performed.Main outcomes and measuresThe primary outcomes were the risk ratio (RR) and the risk difference (RD) for achieving PASI of 2 or lower after 12 months of therapy for secukinumab compared with ustekinumab. Methods to account for missing outcome data were complete case analysis, nonresponder imputation, last observation carried forward, inverse probability of censoring weighting, and multiple imputation. Regulatory and estimate agreement metrics were used to benchmark the effect estimates in this study against those in the CLEAR trial.ResultsA total of 1231 patients were included in the analysis, with 917 receiving ustekinumab and 314 receiving secukinumab. Secukinumab was superior to ustekinumab in all analyses, except under the nonresponder imputation method, in the proportion of participants achieving a PASI of 2 or lower (PS-weighted complete case analysis: RR, 1.28 [95% CI, 1.06-1.55]; RD, 11.9% [1.6-22.1]). All analyses, except for nonresponder imputation, reached regulatory agreement in both PS-matching and PS-weighted analyses.Conclusions and relevanceThis comparative effectiveness study found that secukinumab resulted in more patients achieving a PASI of 2 or lower after 12 months of therapy compared with ustekinumab in patients with psoriasis. Target trial emulation in this study resulted in regulatory and estimate agreement with the CLEAR randomized clinical trial; further such studies may help fill the evidence gap when comparing other systemic therapies for psoriasis.

Project description:ImportanceHigh-cost biologic therapies have transformed the management of immune-mediated inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by measurement of circulating drug levels has been shown to be effective in various settings. However, limited evidence exists for this approach with the interleukin 12 and interleukin 23 inhibitor ustekinumab.ObjectiveTo evaluate clinical utility of therapeutic drug monitoring for ustekinumab in patients with psoriasis.Design, setting, and participantsA prospective observational cohort of 491 adults with psoriasis was recruited to the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study within the British Association of Dermatologists Biologic and Immunomodulators Register from June 2009 to December 2017; samples from some patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria.ExposureSerum ustekinumab level measured at any point during the dosing cycle using an enzyme-linked immunosorbent assay.Main outcomes and measuresDisease activity measured using the Psoriasis Area and Severity Index (PASI) score. Treatment response outcomes were PASI75 (75% reduction in PASI score from baseline [primary outcome]), PASI90 (90% reduction of PASI score from baseline), and absolute PASI score of 1.5 or less.ResultsA total of 491 patients (171 women and 320 men; mean [SD] age, 45.7 [12.8] years) had 1 or more serum samples (total, 853 samples obtained 0-56 weeks from start of treatment) and 1 or more PASI scores within the first year of treatment. Antidrug antibodies were detected in only 17 of 490 patients (3.5%). Early measured drug levels (1-12 weeks after starting treatment) were associated with PASI75 response 6 months after starting treatment (odds ratio, 1.38; 95% CI, 1.11-1.71) when adjusted for baseline PASI score, age, and ustekinumab dose. However, this finding was not consistent across the other PASI outcomes (PASI90 and PASI score of ≤1.5).Conclusions and relevanceThis real-world study provides evidence that measurement of early serum ustekinumab levels could be useful to direct the treatment strategy for psoriasis. Adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome.

Dataset Information

Risk of common infections among individuals with psoriasis in Sweden: A nationwide cohort study comparing secukinumab to ustekinumab.

Purpose

Methods

Results

Conclusion

Publications

Risk of common infections among individuals with psoriasis in Sweden: A nationwide cohort study comparing secukinumab to ustekinumab.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets