Determining tumor necrosis factor-alpha inhibitors (anti-TNF-α) failure is still a challenge in the management of moderate-to-severe psoriasis. Thus, our comprehensive systematic literature review ...aimed to gather information on the criteria used to define anti-TNF-α failure. We also aimed to discover the main reasons for anti-TNF-α failure and define subsequently administered treatments.
We conducted a systematic review following review and reporting guidelines (Cochrane and PRISMA). International (Medline/PubMed and Cochrane Library) and Spanish databases (MEDES, IBECS), and gray literature were consulted to identify publications issued until April 2021 in English or Spanish.
Our search yielded 58 publications. Of these, 37 (63.8%) described the criteria used to define anti-TNF-α primary or secondary failure. Criteria varied across studies, although around 60% considered Psoriasis Area and Severity Index (PASI)-50 criteria. Nineteen (32.8%) reported the reasons for treatment failure, including the lack or loss of efficacy and safety-related problems, mainly infections. Finally, 29 (50%) publications outlined the treatments administered after anti-TNF-α: 62.5% reported a switch to another anti-TNF-α and 37.5% to interleukin (IL)-inhibitors.
Our findings suggest a need to standardize the management of anti-TNF-α failure and reflect the incorporation of new targets, such as IL-inhibitors, in the treatment sequence.
KEY MESSAGES
In the treatment of psoriasis, the primary and secondary anti-TNF-α failure criteria differ widely in the scientific literature.
The strictest efficacy criteria for defining anti-TNF-α failure, or those recommended by guidelines such as PASI75, were underused both in clinical trials and observational studies.
Most studies failed to consider patient-reported outcomes in assessing psoriasis treatment efficacy, which contrasts with recent recommendations on the inclusion of patient-reported HRQoL as a supporting criterion when considering clinical outcomes.
Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The ...combination of a biologic agent and a conventional systemic drug generally methotrexate (MTX) is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis.
The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX.
Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class.
We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002).
The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.
NAVIGATE clinical trial demonstrated a higher rate of Psoriasis Assesment Severity Index (PASI)90 response in patients treated with guselkumab when compared to ustekinumab and an improved response in ...those who switched from ustekinumab to guselkumab due to partial response. The objective of the study is to describe ustekinumab to guselkumab switching in clinical practice. Observational, multicentric, descriptive study including 54 psoriasis patients who switched to guselkumab after treatment with ustekinumab from March 2019 to February 2021. Mean basal PASI with ustekinumab (16.7) was higher than with guselkumab (7.2). Up to 49.01% of patients were able to reach PASI90 with ustekinumab and up to 21.56% had a less frequent dosage regime vs. summary of product characteristics. Main reason to start guselkumab was a loss of ustekinumab cutaneous or articular response (82.36%) but up to 17.64% were switched in order to increase dosage regime efficiency. Six months after starting guselkumab, the absolute PASI was lower than 2 in 72% of patients and 38.5% of them were treated with a reduced dosage regime. Guselkumab doses used by our cohort were 19.5% lower than the expected according to the summary of product characteristics. No adverse events reported. There is no real‐world evidence regarding patients who switched from ustekinumab to guselkumab. A short paragraph in the article by Fougerousse et al, reported 63 patients with a mean basal PASI of 5.3 and similar efficacy rate at week 16 to NAVIGATE. Our study adds practical information regarding efficacy, safety and efficiency through dose optimization in a real‐world cohort.
Background
Few reported studies compare drug survival in moderate‐to‐severe psoriasis vulgaris.
Objectives
To describe and compare drug survival of systemic drugs, including biologic agents ...(infliximab, etanercept, adalimumab and ustekinumab) and classical drugs (acitretin, ciclosporin and methotrexate) in moderate‐to‐severe psoriasis.
Methods
This was a multicenter, prospective, cohort study of patients receiving systemic therapies between 2008 and 2013 in 12 hospitals in Spain. Baseline data and drug discontinuation were collected. Drug survival is presented using Kaplan–Meier survival curves. We compared adjusted risk ratios of serious adverse events (AEs) with results of survival analysis for AEs.
Results
A total of 1956 patients were included for analysis (1240 exposed to biologics during follow‐up and 1076 to classic therapies). Median follow‐up time was 3.3 years (0.0–5.1 years). There were 2209 discontinuations out of 3640 therapy cycles started. The main reason for discontinuation was lack of efficacy (36.4%) and remission (27.2%). Biologics showed a higher drug survival than classics and the pattern of survival results for all outcomes (positive or negative) were very similar. Adjusted risk ratios of serious AEs did not agree with results of survival analysis.
Limitations
A limitation is that this is an observational study with potential selection bias.
Conclusion
Survival as a proxy measure of drug safety in psoriasis is inadequate.
The aim of this study was to generate practical recommendations to assist rheumatologists and dermatologists in the management of cardiovascular (CV) comorbidities in patients with moderate-to-severe ...psoriasis (MS-PSO) and psoriatic arthritis (PsA). A two-round Delphi study was conducted. A panel of experts rated their agreement with a set of statements (
n
= 52) on a nine-point Likert scale (1 = totally disagree; 9 = totally agree). Statements were classified as inappropriate (median 1–3), irrelevant (median 4–6) or appropriate (median 7–9). Consensus was established when at least two-thirds of the panel responded with a score within any one range. A total of 25 experts, 60% rheumatologists and 40% dermatologists, participated in two consultation rounds. There was overall unanimity on the appropriateness of an initial assessment for CV risk factors in all patients with MS-PSO and PsA. Most panelists (88.0%) also supported the evaluation of patients’ psychological and physical status. Additionally, most panelists (72.2%) agreed on a novel sequential approach for the management of CV comorbidities. This sequence starts with the assessment of hypertension, diabetes and dyslipidemia along with the identification of depression and anxiety disorders. Once these factors are under control, smoking cessation programs might be initiated. Finally, if patients have not met weight loss goals with lifestyle modifications, they should receive specialized treatment for obesity. This study has drawn up a set of practical recommendations that will facilitate the management of CV comorbidities in patients with MS-PSO and PsA.
Limited information is available regarding the risk of incident liver disease in patients with psoriasis receiving systemic therapies.
To describe the liver safety findings of conventional and modern ...systemic therapies for moderate-to-severe psoriasis, and to compare the relative incidence rates of hepatic adverse events (AEs) for each drug.
All the patients on the BIOBADADERM registry were included. Crude and adjusted incidence rate ratios (cIRR and aIRR, respectively) of hepatic AEs, using anti-TNF drugs as reference, were determined. Outcomes of interest were hypertransaminasemia, nonalcoholic fatty liver disease (NADFLD) and a group of other, less represented, hepatic AEs.
Our study included 3,171 patients exposed to systemic drugs (6279 treatment cycles). Incident hypertransaminasemia was the most frequent hepatic AE (incidence rate of 21 per 1000 patients-years CI 95% 18-23), followed by NAFLD (8 cases per 1000 patients-years 95% CI 6-10). Methotrexate (aIRR 3.06 2.31-4.4; p = 0.000) and cyclosporine (aIRR 2.37 1.05-5.35; p = .0378) were associated with an increased risk for hypertransaminasemia when compared to anti-TNF-α agents. No differences were observed between different groups of biologics. Conventional therapies were not associated with new incident NAFLD.
Comparative information of the incidence of hepatic AEs could facilitate drug selection in moderate-to-severe psoriasis.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Registry studies broadly describing the safety of systemic drugs in psoriasis are needed.
To describe the safety findings of the systemic drugs acitretin, adalimumab, apremilast, cyclosporine, ...etanercept, infliximab, methotrexate, secukinumab, and ustekinumab used for the treatment of moderate to severe psoriasis in patients included in the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry.
The incidence rate ratio (IRR) and adjusted IRR (including propensity scores) of identified adverse events for each drug, using methotrexate as reference, were determined by means of a prospective cohort.
Our study included 2845 patients (8954 treatment cycles; 9642 patient-years). Ustekinumab and secukinumab had the lowest rate of adverse events for several of the system organ classes, with a statistically significant decreased rate ratio (IRR of <1), whereas cyclosporine and infliximab had the highest, with an increased rate ratio (IRR of ≥5).
Observational study, drug allocation not randomized, depletion of susceptibles, and prescribed doses not registered.
Our data provide comparative safety information in the real-life setting that could help clinicians selecting between available products.
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