Interleukin-17 Inhibitors Research Articles

Ixekizumab therapy following secukinumab inadequate response in psoriatic arthritis: a case series focusing on axial disease.

There are limited data regarding cycling between interleukin-17 (IL-17) inhibitors in psoriatic arthritis (PsA). We aimed to report the efficacy of an IL-17 inhibitor (ixekizumab-IXE) after inadequate response (IR) of another one (secukinumab-SEC) in patients with PsA. Case series of PsA patients who received IXE after SEC-IR in four rheumatology centers between 1/9/2021 and 1/9/2022 were included. Peripheral arthritis was assessed with disease activity in psoriatic arthritis score (DAPSA) and skin involvement with body surface area (BSA). Axial disease was defined as having both imaging and clinical features and its activity was measured with the ankylosing spondylitis disease activity score (ASDAS). Twenty-four patients (54.2% female, mean [SD] age: 51.6 [14.1]) who were SEC-IR and received IXE either immediately (n = 11) or after ≥ 1 interposed biologic disease modifying anti-rheumatic drug (bDMARD) (n = 13) were included. Patients were followed on IXE for a mean [SD] period of 9.6 [4.9] months. Among patients with peripheral arthritis (n = 24), the mean [SD] DAPSA decreased from 22.8 [8.6] to 13.6 [7.8] during follow-up (p = 0.0001) with 62.5% of patients showing improvement in the DAPSA disease activity categories. For patients with axial involvement (n = 16), a clinically meaningful improvement (Δ ≥ 1.1 in ASDAS) was noted in 50% (8/16), while dactylitis and enthesitis resolution was observed in 60% (3/5) and 83% (5/6) of patients, respectively. Regarding psoriasis, the mean [SD] BSA of involved skin decreased from 8.7 [8.7] to 2.4 [3.3] (p = 0.001). In this case series, treatment with IXE after inadequate response to another IL-17 inhibitor (SEC) was efficacious in a real-world setting in patients with PsA, including axial disease.

Interleukin-17 vs. Interleukin-23 Inhibitors in Pustular and Erythrodermic Psoriasis: A Retrospective, Multicentre Cohort Study

Pustular and erythrodermic psoriasis are rare and difficult-to-treat conditions. It has recently been shown that interleukin (IL)-17 inhibitors can be very effective among patients with these forms of psoriasis; however, the potential of IL-23 inhibitors is largely unknown. The aim of this multicentre, retrospective study was to compare the safety, effectiveness, and drug survival of IL-17 and IL-23 inhibitors among patients affected by these rare forms of psoriasis. The study involved 27 patients with erythrodermic psoriasis and 59 with pustular psoriasis (36 with generalised pustular psoriasis and 23 with palmoplantar pustular psoriasis) treated with an IL-17 or IL-23 inhibitor. The effectiveness of the two drug classes was assessed using the disease-specific Psoriasis Area Severity Index (PASI) and the Investigator Global Assessment, which were evaluated at different time points. There was a consistent trend towards a higher rate of PASI 100 responses in the patients treated with IL-17 inhibitors compared with those treated with IL-23 inhibitors, and the other efficacy outcomes showed a similar trend. There was no significant between-drug class difference in efficacy at any of the time points in the erythrodermic psoriasis cohort, whereas PASI 90 and PASI 100 response rates were significantly higher among the pustular psoriasis patients receiving IL-17 inhibitors at week 12 (IL-23 19% vs. IL-17 54% and IL-23 6% vs. IL-17 40%, respectively) and the percentage of responders to IL-17 inhibition was significantly higher at week 24 (IL-23 25% vs. IL-17 74%). In conclusion, it is therefore reasonable to assume that IL-17 and IL-23 inhibitors are both effective when treating pustular and erythrodermic psoriasis.

Treatment patterns and healthcare costs among patients with psoriasis initiating apremilast or biologics: a retrospective claims database cohort analysis

ObjectiveThis study aimed to compare treatment patterns and healthcare costs for patients with psoriasis who initiate apremilast, tumor necrosis factor inhibitor, or interleukin inhibitor.MethodsThis retrospective cohort study used Optum Clinformatics® Data Mart to identify propensity score–matched patients initiating apremilast, tumor necrosis factor inhibitors, or interleukin inhibitors, with 12-month baseline and 24-month follow-up data. Switch, discontinuation, persistence, healthcare resource utilization, and total healthcare costs were assessed.ResultsTwenty-four-month switch rates were highest for tumor necrosis factor inhibitors (32%), followed by apremilast (21%) then interleukin inhibitors (14%). Mean (SD) per-patient-per-month costs for switchers were lowest for apremilast ($4213 [$2304]), higher for tumor necrosis factor inhibitors ($5274 [$2280]), and highest for interleukin inhibitors ($5539 [$2296]; p < .001), primarily attributable to pharmacy costs: $3466 (apremilast), $4432 (tumor necrosis factor inhibitor), and $4721 (interleukin inhibitor).LimitationsPsoriasis severity is absent from claims data; cost outcomes may be influenced by more severe psoriasis being more costly.ConclusionSwitching psoriasis treatment is common and increases over time. Apremilast initiators had lower switch rates and costs compared with tumor necrosis factor inhibitors, despite lower effectiveness reported in previous studies, perhaps indicating patient preference for oral treatment. Additional oral options may be desirable for this population.

Multi-modality data-driven analysis of diagnosis and treatment of psoriatic arthritis

Psoriatic arthritis (PsA) is associated with psoriasis, featured by its irreversible joint symptoms. Despite the significant impact on the healthcare system, it is still challenging to leverage machine learning or statistical models to predict PsA and its progression, or analyze drug efficacy. With 3961 patients’ clinical records, we developed a machine learning model for PsA diagnosis and analysis of PsA progression risk, respectively. Furthermore, general additive models (GAMs) and the Kaplan–Meier (KM) method were applied to analyze the efficacy of various drugs on psoriasis treatment and inhibiting PsA progression. The independent experiment on the PsA prediction model demonstrates outstanding prediction performance with an AUC score of 0.87 and an AUPR score of 0.89, and the Jackknife validation test on the PsA progression prediction model also suggests the superior performance with an AUC score of 0.80 and an AUPR score of 0.83, respectively. We also identified that interleukin-17 inhibitors were the more effective drug for severe psoriasis compared to other drugs, and methotrexate had a lower effect in inhibiting PsA progression. The results demonstrate that machine learning and statistical approaches enable accurate early prediction of PsA and its progression, and analysis of drug efficacy.

Efficacy and safety of IL inhibitors, TNF-α inhibitors, and JAK inhibitors in patients with ankylosing spondylitis: a systematic review and Bayesian network meta-analysis.

Biologics and Janus kinase (JAK) inhibitors are commonly used to improve ankylosing spondylitis (AS) symptoms if conventional treatments are ineffective or unsuitable. This systematic review aimed to compare the therapeutic effects and safety of JAK inhibitors, tumor necrosis factor-alpha (TNF-α) inhibitors, and interleukin (IL) inhibitors in patients with AS. We retrieved literature from various databases including Web of Science, Cochrane, Embase, PubMed, China National Knowledge Infrastructure, Weipu Journal Database, SinoMed, and WanFang Data up to February 1, 2023, and evaluated the quality of the included RCTs using the Cochrane risk-of-bias tool. R 4.1.3, STATA 15.1 were employed for network meta-analyses. We identified 48 eligible articles including 8,937 patients. Ten articles were rated as "low risk", 5 as "high risk", and the others as "some concerns". In terms of efficacy, IL-17, IL-6, and JAK inhibitors were compared with TNF-α inhibitors in ASAS20 (RR =0.81, 95% CI: 0.66-0.98; RR =0.57, 95% CI: 0.35-0.95; RR =0.77, 95% CI: 0.60-0.99). IL-6 inhibitors were compared with TNF-α inhibitors in ASAS5/6 (RR =0.39, 95% CI: 0.16-0.98). IL-23, JAK inhibitors were compared with TNF-α inhibitors in BASDAI50 (RR =0.35, 95% CI: 0.20-0.60; RR =0.70, 95% CI: 0.49-0.98). IL-17 inhibitors were compared with IL-23 and IL-6 inhibitors in BASFI (MD =-1.05, 95% CI: -1.65--0.51; MD =-1.46, 95% CI: -2.02--0.97). In terms of safety, IL-6 inhibitors were compared with JAK, TNF-α inhibitors in AEs (RR =1.38, 95% CI: 1.06-1.88; RR =1.30, 95% CI: 1.01-1.70). TNF-α inhibitors are significantly superior to both IL and JAK inhibitors, and may be the preferable option to deal with the rapid progression of AS and severe functional limitations. IL-17 inhibitors may better improve the BASDAI50 response compared with JAK, IL-23, and TNF-α inhibitors. The efficacy and safety of IL-6 inhibitors are inferior to other types of drugs, indicating the low efficacy and high risk of IL-6 inhibitors.

Eksfolyatif keilit tedavisinde tildrakizumab

Exfoliative cheilitis is an inflammatory condition that can significantly impair quality of life. This is the first reported case of an interleukin-23 inhibitor, tildrakizumab, for the treatment of a chronic, refractory case of exfoliative cheilitis.

Economic Evaluation of Selected Interleukin Inhibitors Versus Methotrexate for Moderate-to-Severe Plaque Psoriasis From the Philippine Payer Perspective

ObjectivesWe conducted an economic evaluation of interleukin inhibitors (ILIs) guselkumab, ixekizumab (IXE), secukinumab (SEC), and ustekinumab to a methotrexate (MTX) comparator for biologic-naive adult Filipino patients with moderate-to-severe chronic plaque psoriasis. MethodsA 1-year decision tree and 5-year Markov model were used to estimate incremental cost-effectiveness ratios (ICERs) in Philippine pesos (PHP) per Psoriasis Area Severity Index improvement of at least 75%. For health technology assessment purposes, we also estimated the budget impact of subsidies for SEC to a Government of the Philippines (GoP) payer. Deterministic and probabilistic sensitivity analyses were performed. Data sources included global literature and local intervention prices. ResultsAll ILIs were more effective but also more expensive than MTX. In the base case, only IXE and SEC were cost-effective treatments at a gross domestic product–benchmarked threshold, yielding ICERs of PHP468 098.01 and PHP483 525.32 per PASI responder, respectively. GUS and UST were less likely to be cost-effective throughout a range of simulated thresholds. ICERs were most responsive to discontinuation rates and drug prices. Full subsidy of SEC for 5 years would cost the GoP PHP1.83 billion more than a similar subsidy for MTX. ConclusionsILIs were clearly more effective than MTX, but only IXE and SEC were potentially cost-effective for a GoP payer. Any case in which SEC is fully subsidized is more expensive to the GoP than the base case. This study was limited by a lack of country-specific effectiveness data, underestimation of comparator costs, exclusion of noncutaneous and quality-of-life effects, and indirect costs.

Interleukin-17 Inhibitor in Treatment of Psoriasis during COVID-19 Pandemic: An Ambispective Study

Introduction: Psoriasis is a genetically mediated chronic inflammatory disease that is frequently associated with metabolic co-morbidities. These metabolic co-morbidities have a huge impact in deciding the appropriate immunosupressant of choice in the current scenario of Coronavirus Disease (COVID19) pandemic. Treatment of psoriasis especially with biologicals is challenging during covid pandemic since immunosuppressive therapy might interfere with antiviral immunity. Aim: To report the safety profile of Interleukin-17 (IL-17) inhibitor, namely injection secukinumab in patients of psoriasis vulgaris during COVID-19 pandemic. Materials and Methods: An ambispective interventional study was performed on 23 patients of psoriasis who were administered secukinumab at a dose of 300 mg subcutaneously during COVID19 pandemic.The study was conducted at the Department of Dermatology, Madras Medical College, Chennai, Tamil Nadu, India among the patients attending the psoriasis clinic between the July 2021 to March 2022. The demographic characteristics of the study group, previous treatment for psoriasis and the relationship between risk of COVID-19 infection and secukinumab were noted. Efficacy of secukinumab was calculated using Psoriasis Area and Severity Index (PASI) scores. Statistical analysis was conducted with Statistical Package for Social Sciences (SPSS) statistics software version 21.0 by Fischer’s-exact test. Results: Out of 23 patients, 17 patients (11 males, six females) completed full course of nine doses (five weekly doses followed by four monthly doses) of secukinumab. The PASI 75 and PASI 90 were achieved in 9 (52.94%) and 8 (29.41%) patients respectively at the end of 12 weeks. None of the patients developed COVID-19 infection during the course of treatment and three months following therapy. Patients with psoriasis who had a history of COVID-19 infection did not show signs of reinfection when started on secukinumab. Both inactivated vaccine (Covaxin) and vector based vaccine (Covishield) were found to be safe in concomitant use with secukinumab. Conclusion: Secukinumab is found to be safe and effective in psoriasis treatment during COVID-19 pandemic. There is no increased risk of COVID-19 infection or reinfection, COVID-19 associated hospitalisation and mortality among patients with psoriasis administered with secukinumab. The drug can also be safely used with COVID-19 vaccines.

The use of interleukin-23 inhibitors to treat immune-related psoriasis induced by immune checkpoint inhibitors and in patients with active cancer: A case series and review of the literature

Immune checkpoint inhibitors have revolutionized cancer treatment but can induce immune-related adverse events including psoriasis. Managing immune-related psoriasis or psoriasis in a cancer setting is challenging with a lack of safety data. We describe three patients receiving interleukin-23 inhibitors to manage psoriasis in an active cancer setting, including one with immune-related psoriasis. Interleukin-23 inhibitors were effective for all patients. While being on interleukin-23 inhibitors, one patient had cancer partial response, one had deep partial response but then progressed and died from her melanoma, and one suffered melanoma progression.

Biologic and Small-Molecule Therapies for Moderate-to-Severe Psoriasis: Focus on Psoriasis Comorbidities.

Psoriasis is a systemic immune-mediated disease associated with an increased risk of comorbidities, such as psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory bowel disease, psychiatric disorders, and malignancy. In recent years, with the advent of biological agents, the efficacy and safety of psoriasis treatments have dramatically improved. Presently, tumor necrosis factor-α inhibitors, interleukin-17 inhibitors, interleukin-12/23 inhibitors, and interleukin-23 inhibitors are approved to treat moderate-to-severe psoriasis. Small-molecule inhibitors, such as apremilast and deucravacitinib, are also approved for the treatment of psoriasis. Although it is still unclear, systemic agents used to treat psoriasis also have a significant impact on its comorbidities by altering the systemic inflammatory state. Data from clinical trials and studies on the safety and efficacy of biologics and small-molecule inhibitors provide important information for the personalized care and treatment for patients with psoriasis. Notably, treatment with interleukin-17 inhibitors is associated with new-onset or exacerbations of inflammatory bowel disease. In addition, great caution needs to be taken when using tumor necrosis factor-α inhibitors in patients with psoriasis with concomitant congestive heart failure, multiple sclerosis, and malignancy. Apremilast may induce weight loss as an adverse effect, presenting also with some beneficial metabolic actions. A better understanding of the characteristics of biologics and small-molecule inhibitors in the treatment of psoriasis comorbidities can provide more definitive guidance for patients with distinct comorbidities.

Drug switching in axial spondyloarthritis patients in Germany - a social listening analysis.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease which primarily affects the axial skeleton resulting in chronic back pain and stiffness. According to the guideline, the first-line treatment includes non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and non-pharmacological treatment. Second line treatment involves biological disease-modifying antirheumatic drugs (bDMARDs) such as tumour necrosis factor and interleukin-17 inhibitors. The aim of this social media listening research project was to analyse switches of medication and the reasons thereof to gain valuable insights into real-life journeys of patients suffering from axSpA. Publicly available posts in German-speaking disease-specific forums were scanned for disease-specific keywords and commonly used drugs by axSpA patients on the Permea platform. Posts containing at least two key words were selected and switches between medications were manually labelled. A total of 287 scraped posts between 01 July 2010 and 04 Feb 2022 were analysed. The largest group of described medication switches was initially using bDMARDs. Switches to a different bDMARD, termination of medication and switches to glucocorticoids were most frequently named. Patients on NSAIDs switched to glucocorticoids, a different NSAID or bDMARD, whereas patients on csDMARDs most frequently changed to bDMARDs. In all medication groups the main reason for switching was insufficient efficacy and side effects. Additionally, for the medication groups bDMARDs, csDMARDs and corticosteroids, pregnancy and lactation were given as a reason for switching, whereas patients in the NSAID group never mentioned pregnancy and breastfeeding as a reason for switching treatment. Our analysis shows medication switches based on real-life patient experiences shared with peers in a social listening setting. We also show medication switches differing from advised guidelines. Gathering real-life insights into patients' journey dealing with chronic diseases allows us to understand, and thereby improve patient care and treatment.

Acrodermatitis Continua of Hallopeau: A Diagnostic Challenge.

Acrodermatitis Continua of Hallopeau: A Diagnostic Challenge.

Drug Retention Rate and Factors Associated with Discontinuation of Interleukin-17 Inhibitors in Patients with Axial Spondyloarthritis.

To assess the drug retention rate of interleukin-17 inhibitors (IL-17is) over long-term observation in patients with axial spondyloarthritis (axSpA) in whom treatment with tumor necrosis factor inhibitors (TNFis) failed and to determine baseline factors associated with discontinuation of IL-17is. This retrospective cohort study included 68 patients with axSpA started on IL-17is after an inadequate response or intolerance to ≥1 TNFis. Drug retention rates at 1, 2, and 3 years were assessed. Baseline (i.e., at initiation of IL-17is) factors associated with discontinuation of IL-17is were evaluated using multivariable Cox proportional hazard regression analysis. Over 1933.9 person-months of observation in 68 patients, discontinuation of IL-17is occurred in 27 (39.7%) patients. Twenty (29.4%) patients discontinued IL-17is because of ineffectiveness, and 7 (10.3%) patients discontinued IL-17is because of adverse events. The 1-year, 2-year, and 3-year drug retention rates for IL-17is were 71.9%, 66.5%, and 62.0%, respectively. Current smoking was associated with a higher risk of IL-17is discontinuation [adjusted hazard ratio (HR)=2.256, 95% confidence interval (CI)=1.053-4.831, p=0.036], while previous use of ≥3 TNFis (vs. 1) was significantly associated with a lower risk of IL-17is discontinuation (adjusted HR=0.223, 95% CI=0.051-0.969, p=0.045). In patients with axSpA in whom TNFis failed, the long-term drug retention rate of IL-17is appears to be acceptable, with a 3-year drug retention rate of approximately 60%. Current smoking was associated with a higher risk of discontinuing IL-17is, whereas previous use of ≥3 TNFis was associated with a lower risk of discontinuing IL-17is.

PsABIOnd Study and eDaily Substudy Design: Long-Term Effectiveness and Safety of Guselkumab and IL-17 Inhibitors in Routine Clinical Practice in Patients with Psoriatic Arthritis.

Randomised clinical studies in psoriatic arthritis (PsA) do not always reflect patients in routine clinical practice. Large-scale data from routine practice are needed to better understand drug persistence, effectiveness and long-term safety of therapeutic agents. PsABIOnd is an international, prospective, observational study designed to collect long-term routine care data in patients with PsA who receive guselkumab (an interleukin-23 [IL-23] inhibitor) or an interleukin-17 (IL-17) inhibitor. Adult patients (≥ 18years) with a confirmed diagnosis of PsA who are starting guselkumab or any approved IL-17 inhibitor as a first, second, third or fourth line of PsA treatment and who provide written informed consent will be eligible to participate. Participants will be followed for a maximum of 36months (+3months) from the start of treatment. Study visits will occur in line with the standard of care, approximately every 6months, plus an additional visit at 3months after the start of treatment. eDaily by PsABIOnd- aneHealth substudy, will document the impact of these treatments on wellbeing and symptoms in a subgroup of participants over a 24-week (+4weeks) observation period on treatment. The primary objective of PsABIOnd is to evaluate treatment persistence with guselkumab and IL-17 inhibitors. Data sources will include validated electronic patient-reported outcomes (ePROs) and physician-completed assessments. Safety data will be collected through reporting adverse events. The eDaily by PsABIOnd substudy will use wearable and digital technologies for continuous activity and sleep monitoring, and frequent patient eDiary and ePRO collection to provide a more detailed and comprehensive picture of PsA. ClinicalTrials.gov identifier: NCT05049798.

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disor ders; gastrointestinal disorders, neurological disorders, and allergic reactions; and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia; neutropenia is also characteristic of a number of interleukin inhibitors. Haemo static adverse reactions to anticoagulants depend on the patient’s dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.

The Yin-Yang Pharmacomicrobiomics on Treatment Response in Inflammatory Arthritides: A Narrative Review.

(1) Background: Gut microbiota (GM) is the set of microorganisms inhabiting the gastroenteric tract that seems to have a role in the pathogenesis of rheumatic diseases. Recently, many authors proved that GM may influence pharmacodynamics and pharmacokinetics of several drugs with complex interactions that are studied by the growing field of pharmacomicrobiomics. The aim of this review is to highlight current evidence on pharmacomicrobiomics applied to the main treatments of Rheumatoid Arthritis and Spondyloarthritis in order to maximize therapeutic success, in the framework of Personalized Medicine. (2) Methods: We performed a narrative review concerning pharmacomicrobiomics in inflammatory arthritides. We evaluated the influence of gut microbiota on treatment response of conventional Disease Modifying Anti-Rheumatic drugs (cDMARDs) (Methotrexate and Leflunomide) and biological Disease Modifying Anti-Rheumatic drugs (bDMARDs) (Tumor necrosis factor inhibitors, Interleukin-17 inhibitors, Interleukin 12/23 inhibitors, Abatacept, Janus Kinase inhibitors and Rituximab). (3) Results: We found a great amount of studies concerning Methotrexate and Tumor Necrosis Inhibitors (TNFi). Conversely, fewer data were available about Interleukin-17 inhibitors (IL-17i) and Interleukin 12/23 inhibitors (IL-12/23i), while none was identified for Janus Kinase Inhibitors (JAKi), Tocilizumab, Abatacept and Rituximab. We observed that microbiota and drugs are influenced in a mutual and reciprocal way. Indeed, microbiota seems to influence therapeutic response and efficacy, whereas in the other hand, drugs may restore healthy microbiota. (4) Conclusions: Future improvement in pharmacomicrobiomics could help to detect an effective biomarker able to guide treatment choice and optimize management of inflammatory arthritides.

Comparative pharmacoeconomic effectiveness of interleukin-17 inhibitors for the treatment of ankylosing spondylitis

Objective – to compare the clinical efficacy and cost-effectiveness of IL-17 inhibitors (SEC, IXE, NTK) in the treatment of adult patients with ankylosing spondylitis (AS) in the healthcare system of the Russian Federation.Material and methods. The study is a sub-analysis of a previously published systematic review and network meta-analysis of the comparative efficacy of biologics in adult patients with AS in the Russian Federation. NNT values were calculated for BASDAI 50 and ASAS 20/40 after 16 weeks of therapy for all studied drugs. CpR was estimated for each biologic after 16 weeks and one year of therapy. Additionally, we carried out an assessment of the financial burden of the most cost-effective strategies for the treatment of AS.Results. The use of NTK is characterized by an average of no more than three patients needed to treat to achieve one ASAS 20/40 or BASDAI 50 response, while on IXE and SEC – no more than 4–5 patients need to be treated, depending on the estimated effectiveness criterion. According to CpR estimate, NTK is the most cost-effective IL-17 inhibitor for the treatment of AS, both after 16 weeks and after one year of therapy.Conclusion. The obtained results make it possible to compare the effectiveness of IL-17 inhibitors from a clinical and economic points of view and can be used both in decision making process of treatment strategies for individual patients, and at the population level – when deciding on the reimbursement of drugs

Treatment Options for Juvenile Pityriasis Rubra Pilaris.

Pityriasis rubra pilaris represents a group of familial and acquired disorders of cornification that affect both adult and pediatric patients. Treatment options are difficult to assess through clinical trials, given the rarity of the disorder and its tendency for spontaneous remission. Case reports and case series are therefore the primary means of assessment. Because of the heterogeneity of the disease, there is no universal approach to treatment, and multiple agents may need to be trialed to achieve disease control. At present, topicals are used for most pediatric patients, though monotherapy with topicals is only effective for less severe disease. Despite concerns over their side-effect profiles, oral retinoids are generally accepted as a first-line systemic therapy. However, interleukin-17 inhibitors and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, may soon become first-line systemic treatment as well, given their efficacy and relative safety in trials thus far. Ustekinumab, in particular, is emerging as a first-line agent for patients with pityriasis rubra pilaris with CARD14 gene variations. When these therapies fail, second-line and adjunctive therapies to consider include tumor necrosis factor-alpha inhibitors, methotrexate, and phototherapy. However, further investigation is necessary to assess the safety and efficacy of many of these agents in juvenile pityriasis rubra pilaris.

The Use of IL-17 and IL-23 Inhibitors in Swedish Clinical Practice: A Register-Based Analysis

Background: Interleukin (IL) inhibitors have made completely cleared skin achievable for many patients with moderate to severe psoriasis in clinical trial settings. Few observational studies assess treatment response in accordance with treatment goals in guidelines. Objectives: The aim of the study was to analyze the treatment response of IL-17/IL-23 inhibitors in clinical practice and the proportions of patients that reach the treatment target of the Psoriasis Area and Severity Index (PASI) < 3 and the Dermatology Life Quality Index (DLQI) ≤5. Methods: A longitudinal, observational study based on the Swedish National Registry for Systemic Treatment of Psoriasis, PsoReg. Patients using IL-17/IL-23 inhibitors with assessments of PASI, DLQI, and EQ-5D before (maximum 6 months) and after (3–12 months) initiation of IL-17/IL-23 were included. Results: In total, 333 patients using IL-17/IL-23 inhibitors were included. Eighty percent (n = 266) received IL-17 inhibitors, and 20% (n = 67) received IL-23 inhibitors. Sixty-six percent of patients reached both PASI <3 and DLQI ≤5, 23% reached one target, and 11% reached none. The mean (SD) PASI, DLQI, and EQ-5D improvements were 6.75 (6.99), 7.14 (7.97), and 0.126 (0.296), respectively. There was no statistically significant difference in outcomes between IL-17 and IL-23 inhibitor treatment groups. Conclusions: IL-17/IL-23 inhibitors are effective in clinical practice, but there is still an unmet therapeutic need in moderate to severe psoriasis.

Effectiveness of Guselkumab Therapy among Patients with Plaque Psoriasis with Baseline IGA Score ≥ 2 in the CorEvitas Psoriasis Registry.

In clinical trials, treatment with the interleukin-23 inhibitor guselkumab was associated with significantly improved disease severity and patient-reported outcome measures (PROMs) among patients with moderate-to-severe plaque psoriasis. However, limited information is available regarding the real-world effectiveness of guselkumab among patients with psoriasis of mild, moderate, and severe Investigator's Global Assessment (IGA) severities living in the USA and Canada. Patients participating in the CorEvitas Psoriasis Registry between 18 July 2017 and 10 July 2019 who met the following criteria were included: IGA ≥ 2 (mild or greater disease severity), initiated guselkumab at a registry (index) visit, and had a registry follow-up visit after persistent guselkumab treatment for 9 to 12months. Data were collected for patient demographics, disease characteristics, treatment history, disease activity, and PROMs. At follow-up, outcome measure response rates and mean changes from the index visit were calculated. Among 130 patients, the mean age was 50.2years, 39.2% were female, and 56.9% had a body mass index ≥ 30kg/m2. Mean psoriasis duration was 17.5years and 79.2% of patients had previously received one or more biologic therapy. At the index visit, mean IGA, Psoriasis Area Severity Index (PASI), and Dermatology Life Quality Index (DLQI) scores were 3.0, 9.9, and 8.0, respectively. At follow-up, IGA0/1 and IGA 0 were achieved by 64.6% and 36.2% of patients, respectively. PASI75, 90, and 100 were achieved by 61.5%, 46.9%, and 36.9% of patients; 55.4% had maintained or achieved DLQI0/1. Mean improvements were observed in all evaluated disease activity outcomes and PROMs, with all differing significantly from zero except for the percent of work hours missed due to psoriasis. In this real-world study, patients with a baseline IGA score ≥ 2 experienced improvements in disease activity and PROMs after 9-12months of persistent guselkumab treatment.