Interleukin-17 Inhibitors Research Articles

Latent Tuberculosis Screening Among New Users of a Biologic or Targeted Synthetic Disease-Modifying Antirheumatic Drug: Gaps in Screening Overall and Among Janus Kinase Inhibitors.

We combined claims and electronic health record (EHR) data to provide contemporary and accurate estimates of latent tuberculosis (TB) screening among new users of a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) and assess potential gaps in testing by drug type, patient characteristics, and practice. Our denominator population was patients in the Rheumatology Informatics System for Effectiveness (RISE) registry and Medicare using a b/tsDMARD in 2018 without a claim or prescription in the year prior. TB screening was assessed in both Medicare and RISE 1 and 3 years before the medication start date. We calculated the proportion screened overall, by medication class, and by practice. We tested for demographic differences in screening using logistic regression. In the year before drug starts, 65.6% of patients had any TB screening; in a 3-year window, 72.9% had any TB screening. Rates of screening within 1 year by drug type were greater or equal to the overall screening rate for most drugs except for JAK inhibitors (JAKis) (46%) and interleukin-17 inhibitors (IL-17is) (11.5%). A lower proportion of Hispanic and Asian patients were screened compared with White patients. Practice screening rates ranged from 20.0% to 92.9% of patients within 1 year. We report higher screening rates than have previously been published because of combining claims and EHR data. However, important safety gaps remain, namely, reduced screening among new users of a JAKi or IL-17i and among Asian and Hispanic patients, as well as low-performing practices. Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed.

Anticytokine therapy with interleukin-17 in patients with moderate and severe psoriasis

Clinical observations of three patients aged 26, 43 and 37 years with severe psoriasis and psoriatic arthritis are presented. Clinical examples show the experience of effective treatment of patients with psoriasis and psoriatic arthritis using anti-cytokine therapy with an interleukin-17 inhibitor, initiated when the disease progresses. The clinical picture of the presented observations was characterized by an aggressive course of the skin and articular process, torpidity to basic therapy, despite the young age of the patients. It has been shown that the early termination of the progression of the inflammatory process in psoriasis with the use of genetically engineered biological therapy with secukinumab leads to a decrease in symptoms, both on the part of the skin and manifestations of the disease on the part of the musculoskeletal system. The high efficacy and safety of the drug allow complete control of the disease and improve the quality of life in patients suffering from severe forms of dermatosis.

Advantages of IL-17 inhibitor, ixekizumab, in the treatment of severe psoriasis

Psoriasis is a common immune-mediated disease, often accompanied by inflammatory and metabolic disorders. About 20–30% of patients have moderate to severe psoriasis and require systemic methods of treatment, which include conventional, targeted and genetically engineered biological drugs (GEBDs). When selecting a biological agent, a number of factors must be considered related to the disease, patient and therapy. Assessment of severity and activity, area of skin affected, frequency of relapses, pruritus and other symptoms, the presence of comorbidities, especially psoriatic arthritis (PsA), are important. The presence of comorbidities that may contribute to or interfere with the use of GEBD is the main factor determining personalised therapy. Personalised treatment implies maximum efficacy and minimum risk of side effects. In addition, it is possible to modify the course of the disease, inducing long-term remission and preventing the development of PsA, which is possible in case of timely prescription of GEBD. To date, several classes of GEBDs are available in the arsenal of dermatovenerologists, among which interleukin (IL) inhibitors have the highest efficacy and safety. The drug ixekizumab is a member of the IL-17 inhibitor group, a monoclonal antibody of the IgG4 class that binds to IL-17A with high affinity and specificity. The drug has shown high efficacy and reliable safety profile in the treatment of psoriasis and PsA within the framework of numerous clinical trials and studies of real clinical practice, including in patients with an aggravated comorbid background and with involvement of hard-to-treat localisations. The presented article presents key data of safety and efficacy studies of ixekizumab therapy, describes a clinical case of successful treatment of a patient with psoriasis and psoriatic onychodystrophy. Timely initiation of therapy helped to stop the progression of the disease and significantly improved the quality of life of the patient. Thus, the presented data confirm the advantages of ixekizumab in psoriasis treatment.

Experience with interleukin-23 inhibitor guselkumab using in patients with severe psoriasis and the impact of the disease on the psycho-emotional background

Psoriasis is a chronic immune-mediated disease that leads not only to damage to the skin and its appendages, but is also associated with concomitant systemic diseases, including damage to the musculoskeletal system, cardiovascular pathologies, kidney disease, metabolic syndrome and changes in the nervous system. Not long ago, a term was introduced to unite psoriasis and concomitant comorbid diseases – psoriatic disease. Recently, special attention has been paid to assessing the psychoemotional state and quality of life of patients with psoriasis who bear the burden of a chronic disease. It is no secret that any skin disease significantly worsens the quality and standard of life of the patient and can lead to social and professional stigma and discrimination, and a number of restrictions. Psoriatic disease is recognized as a multisystem inflammatory disease and a holistic approach to treatment is recommended, focusing on comorbidities, including mental health, psychosocial well-being and quality of life. The Dermatological Life Quality Index (DLQI) is one of the most convenient indices that allows you to assess the severity of the burden of chronic skin diseases, including psoriasis, on a person’s daily activities; a correlation was found between the severity of psoriasis, the presence of concomitant diseases, especially psoriatic arthritis and the DLQI level. DLQI is higher in patients with moderate to severe psoriasis, in patients with mild psoriasis (low PASI index), but with damage to socially significant areas of the skin (face, hands and feet, scalp, genitals, nail plates), in patients with active manifestations of psoriatic disease in the form of concomitant diseases, which complicates the choice of drug for treatment. The availability, effectiveness, and treatment regimens of modern drugs play an important role in the psycho-emotional state of patients. Today the biological drugs have been actively used in the treatment of psoriasis, which have a number of advantages compared to drugs of basic anti-inflammatory therapy and phototherapy, and, accordingly, are more effective and are of value for patients who experience emotional discomfort from a chronic skin disease in everyday life. The purpose of this article was to study the prevalence and nature of mental and psychiatric pathologies in patients with psoriasis, the possible improvement of DLQI in patients with psoriasis using a biological drug from the group of interleukin-23 inhibitors guselkumab.

The Evaluation of Effectiveness and Safety of Guselkumab in Patients with Psoriatic Arthritis in a Prospective Multicentre "Real-Life" Cohort Study.

Guselkumab is an interleukin-23 (IL-23) inhibitor licensed for the treatment of psoriatic arthritis (PsA). This study aimed to evaluate the 6-month effectiveness of guselkumab in patients with PsA in a "real-life" multicentre patient cohort. We also estimated the drug retention rate (DRR) of gusulkumab, also assessing the impact of comorbidities and patient clinical characteristics, in a collective 18-month prospective follow-up. Between December 2021 and September 2023, consecutive patients with PsA were evaluated if treated at least for 6months with guselkumab in a prospective multicentre study to evaluate the effectiveness of the drug by means of disease activity index for psoriatic arthritis (DAPSA) and cumulative DRR. A total of 111 patients with PsA were evaluated and treated with guselkumab (age 56.8 ± 9.9, male sex 20.7%). These patients were mainly characterised by active and long-standing PsA with median disease duration of 6.0 (7.0) years (55.9% disease duration ≥ 5years), 55.0% showed comorbidities, 78.4% of patients were previously treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), and 60.4% concomitantly with conventional synthetic DMARDs (csDMARDs). After 6months, a significant reduction of DAPSA was observed (β - 15.47, p = 0.001, 95%CI - 23.15 to - 9.79) with 39.6% of patients achieving a DAPSA ≤ 14. At the end of cumulative follow-up, 71.2% of patients were still treated with guselkumab whereas 24.3% discontinued the drug because of inefficacy. An 18-month DRR of guselkumab of 66.7% was estimated with a mean time of administration of 9.8 ± 4.1months. The results of the DRR were stratified according to patient clinical characteristics. The DRR of guselkumab appeared to be not influenced by long disease duration, comorbidities, obesity, concomitant csDMARDs, and previous bDMARDs. The "real-life" 6-month effectiveness of guselkumab was shown in patients with PsA, mainly characterised by active long-standing disease, previously treated with bDMARDs, and with comorbidities. Furthermore, a good DRR of guselkumab was estimated in the cumulative 18months of follow-up and appeared to be not influenced by long disease duration, comorbidities, obesity, and previous bDMARDs.

A retrospective analysis of 65 patients with acrodermatitis continua of Hallopeau.

There are limited data on acrodermatitis continua of Hallopeau (ACH), particularly among Asian populations. The primary aim was to evaluate the clinical features of ACH and treatment approaches in a sizeable multicentre Asian cohort. We analysed data from adult patients diagnosed with ACH. Of 65 patients with ACH, seven patients had ACH with GPP. Females were more frequently affected in both conditions. Five (71.4%) developed GPP 5-33 years after ACH onset, while two (28.6%) developed GPP concurrently with ACH. The onset age for ACH with GPP (27.9 ± 13.6 years) was earlier than that of isolated ACH (39.8 ± 17.3 years). Metabolic comorbidities were common. ACH exhibited a chronic persistent course. Among systemic non-biologics, acitretin was the most frequently prescribed, followed by ciclosporin and methotrexate. Acitretin and ciclosporin demonstrated similar marked response rates, which surpassed that of methotrexate. Regarding biologics, a marked response was more commonly observed with interleukin-17 inhibitors than with tumour necrosis factor inhibitors. Females are predominant in both conditions. The onset age for ACH among Asian patients is earlier (late 30s) than that for Caucasian patients (late 40s). Interleukin-17 inhibitors may be more effective than tumour necrosis factor inhibitors in managing ACH.

Risk of Infection in Patients With Inflammatory Bowel Disease Treated With Interleukin-Targeting Agents: A Systematic Review and Meta-Analysis.

Patients with inflammatory bowel disease (IBD) are at increased risk of infection. The aim of this study was to assess the cumulative incidence and risk of infection in patients with IBD treated with interleukin (IL)-targeting agents. We searched PubMed, EMBASE, and Web of Science for randomized controlled trials including patients with IBD receiving IL-targeting agents compared with patients receiving placebo or treatment that only differed from the intervention arm in the absence of an IL-targeting agent. The primary outcome of interest was the relative risk (RR) of any-grade and severe infection during the induction phase. There was no difference in risk of any-grade (RR, 0.98; 95% confidence interval [CI], 0.89-1.09) or severe (RR, 0.64; 95% CI, 0.38-1.10) infection in patients receiving any IL-targeting agent compared with the control group. During the maintenance period, the cumulative incidence of any-grade infection in patients receiving IL-12/23p40-targeting agents (mean follow-up 29 weeks) was 34.82% (95% CI, 26.78%-43.32%), while the cumulative incidence of severe infection was 3.07% (95% CI, 0.93%-6.21%). The cumulative incidence of any-grade infection in patients receiving IL-23p19-targeting agents (mean follow-up 40.9 weeks) was 32.16% (95% CI, 20.63%-44.88%), while the cumulative incidence of severe infection was 1.75% (95% CI, 0.60%-3.36%). During the maintenance phase of the included studies, the incidence of infection was 30.66% (95% CI, 22.12%-39.90%) for any-grade and 1.59% (95% CI, 0.76%-2.63%) for severe infection in patients in the control group. There was no difference in risk of infection between patients with IBD who received IL-targeting agents compared with the control group. Case registries and randomized controlled trials reporting the safety of IL inhibitors should provide detailed information about the risk of specific infectious complications in patients with IBD receiving IL-targeting agents.

Эффективность терапии ингибитором интерлейкина-23 гуселькумабом и показатели качества жизни больных псориазом

Эффективность терапии ингибитором интерлейкина-23 гуселькумабом и показатели качества жизни больных псориазом

IL-17A inhibitors alleviate Psoriasis with concomitant restoration of intestinal/skin microbiota homeostasis and altered microbiota function.

Disturbed gut microbiota and associated metabolic dysfunction exist in Psoriasis. Despite the growing use of interleukin-17 inhibitor (anti-IL17) therapy, the effect of anti-IL17 on gut/skin microbiota function is not fully understood in patients with Psoriasis. Therefore, we explored whether Psoriasis is associated with alterations in selected gut/skin microbiota in a study cohort, and a longitudinal cohort study to reveal the effects of IL-17A inhibitor treatment on gut microbiota in Psoriasis. In a case-control study, 14 patients with Psoriasis and 10 age, sex and body mass index-matched Healthy Controls were recruited. Longitudinal mapping of the gut microbiome was performed using 16S rRNA gene sequencing. Mouse models were used to further study and validate the interrelationship between the skin microbiome and the gut microbiome in Psoriasis. PICRUST2 was applied to predict the function of the bacterial community. In Psoriasis patients, gut microbiota dysbiosis was present with increased heterogeneity: decreased Bacteroidota and increased Firmicutes as well as Actinobacteriota predominating in Psoriasis. Escherichia-Shigella enrichment was associated with reduction in serum levels of total bile acid and markers in Apoptotic pathways. After IL-17A inhibitor treatment in Psoriasis patients, longitudinal studies observed a trend toward a normal distribution of the gut microbiome and modulation of apoptosis-related metabolic pathways. Results from a mouse model showed dysregulation of the skin microbiota in Psoriasis characterized by Staphylococcus colonization. The psoriatic gut/skin microbiota exhibits loss of community stability and pathogen enrichment. IL-17A inhibitors restore microbiota homeostasis and metabolic pathways, reduce pro-inflammatory cytokine expression, and alleviate symptoms in patients with Psoriasis.

Efficacy and safety of tildrakizumab in elderly patients: real-world multicenter study (ESTER – study)

Purpose of the article: Interleukin-23 inhibitors, such as tildrakizumab, have emerged as safe and effective options for the management of psoriasis. Yet their efficacy in elderly patients (aged 65 years or more), particularly in those with difficult-to-treat areas involvement, remains insufficiently explored. We conducted this real-life retrospective multicentric observational study to assess the effectiveness of tildrakizumab in elderly patients with moderate-to-severe psoriasis, with involvement of difficult-to-treat areas.Materials and methods: We enrolled forty-nine patients aged 65 years old or more (mean age 73.1 ± 6.0), all treated with tildrakizumab for at least 28 weeks. The effectiveness of tildrakizumab was assessed by Static Physician’s Global Assessment of Genitalia (sPGA-G), fingernail-PGA (f-PGA), palmoplantar PGA (pp-PGA), scalp-specific PGA (sc-PGA), and Psoriasis Area and Severity Index (PASI) scores.Results: Significant improvements in PASI scores were observed within 28 weeks of treatment, with 77.5%, 60%, and 45.2% of patients achieving PASI75, PASI90, and PASI100, respectively. The mean PASI decreased significantly from baseline (13.6 ± 9.9) to 1.3 ± 1.7 at week 28. More than 90% of patients had clear sPGA-G and pp-PGA scores and over 70% had clear f-PGA and sc-PGA scores after 28 weeks.Conclusions: Our findings suggest that tildrakizumab could be a valuable option for the treatment of elderly patients, including those with difficult-to-treat areas involvement.

A258 ULTRASOUND ASSESSMENT OF CROHN’S DISEASE PATIENTS FOLLOWING RISANKIZUMAB INITIATION; BASELINE, 3 AND 6 MONTH FOLLOW UP

Abstract Background Risankizumab (RIS), an interleukin-23 inhibitor specific to the p19 subunit, was approved for the treatment of moderate to severe Crohn’s Disease (CD) in December 2022. Intestinal ultrasound (IUS) is an accurate and well-tolerated modality for evaluating response to therapy. Aims We aim to assess IUS response at 3 and 6 months following RIS therapy. Methods Consecutive patients initiating RIS for CD were recruited to be evaluated by IUS at baseline (within 14 days of initiation), 3 months, and 6 months. Baseline demographics, medication exposure, surgical history, and inflammatory biomarkers were obtained. IUS response (decrease in bowel wall thickness (BWT) ≥ 25%)) and transmural remission (TR) (normalization of BWT normalization, color doppler signal (CDS, modified Limberg (ML) score 0), wall stratification, inflammatory fat) for each segment were evaluated. Paired t-tests compared values at baseline, 3 and 6 months. Results Thirty-three (20, 60.6% female) patients were recruited; 30 completed baseline and 3 month IUS, while 18 patients have 6 month IUS. Median age was 55 years (IQR 39-63), with a 12 year median CD duration (IQR 5-28). Five had inflammatory, 19 stricturing, and 6 fistulizing behaviour. CD distribution was 18 ileal, 1 colonic, and 11 ileocolonic. 20% (6/30) were bio-naïve, while 30% (9/30) had failed ≥ 3 biologics. Baseline mean CRP (4.1 ± 4.9 mg/L) did not significantly differ at 3 months (5.0 ± 6.8 mg/L, p=0.16), nor at 6 months for patients with values available (6.2mg/L ± 8.3, p = 0.38). Of patients with FC concentrations, 3 month mean FC (129.4 ±70 mcg/g) (9 patients) had significantly decreased from baseline (427.6 ± 271 mcg/g) (p=0.008), and similarly at 6 months (9 patients; baseline 396 ± 299 vs. 129 ± 75, p = 0.02). 80.0% (4/5) patients with colonic BWT ampersand:003E 3mm had IUS response (baseline mean BWT 5.6 ±1.4mm vs 3.5 ± 0.8mm at 3 months (p=0.011). IUS response was not achieved in those with ileal CD at 3 months (BWT 6.3 ± 2.1mm vs 3 month 6.0 ± 2.5mm (p=0.31). However, 21.4% (3/14) of ileal CD patients had an IUS response at 6 months. There is a non-significant ileal BWT reduction (5.4 ± 1.6mm) from baseline (6.0 ± 1.7mm) at 6 months. Of the 9 with moderate to severe CDS, 55% (5/9) had reduction to mild CDS by 3 months. TR was achieved by one patient with ileal CD at 6 months. Conclusions IUS response was achieved in 80.0% of CD patients with colonic disease at 3 months follow RIS initiation. IUS response was not detected for ileal CD at 3 months, but detected in 21.4% at 6 months A significant FC reduction by 3 and 6 months was attained. Further prospective patient recruitment and IUS at 6 and 12 months to assess preliminary results and longer-term response is needed. Funding Agencies None

Mirikizumab: A New Therapeutic Option for the Treatment of Ulcerative Colitis.

To review the pharmacologic and clinical profile of mirikizumab in the treatment of moderate to severe ulcerative colitis (UC). A PubMed search was performed from inception to December 2023 using keywords mirikizumab, interleukin-23 inhibitor, and UC. Information was also obtained from package inserts as well as published abstracts. Phase 3 studies plus relevant literature on mirikizumab pharmacologic and clinical profile were reviewed. Mirikizumab approval was based on LUCENT-1 and LUCENT-2. In the phase 3 studies involving patients with moderate to severe UC, mirikizumab, when compared to placebo, resulted in clinical remission in a significantly higher proportion of patients in both the induction and maintenance phase. In addition, mirikizumab met the secondary endpoints of alternate definition of clinical remission, endoscopic remission, glucocorticoid-free clinical remission, histologic-endoscopic mucosal remission, and improvement in bowel urgency status, bowel-urgency remission, and maintenance of clinical remission. Common adverse events noted include infection (15.1%), injection-site reaction (8.7%), nasopharyngitis (7.2%), and headache (3.3%). Mirikizumab is the first selective interleukin 23 (IL-23) inhibitor approved for UC. Additional studies are required to determine how to position mirikizumab in both biologic-naïve and biologic-experienced patients with moderate to severe UC. Mirikizumab provides a novel mechanism of action for the treatment of moderate to severe UC and is another welcomed treatment advance in the treatment arsenal, providing a more selective mechanism of action while maintaining a comparable safety profile.

Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Moderate-to-Severe Psoriasis.

Psoriasis is a common inflammatory immune disorder due to chronic activation of the adaptive and innate immune responses. Therapies for psoriasis target reducing inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-17, and interleukin-22. Patients with inflammatory disorders have reduced metabolism by cytochrome P450 enzymes in the liver. The pharmacokinetic and pharmacodynamic changes due to psoriasis also have an impact on reaching therapeutic concentrations of the drug. Pharmacokinetic and pharmacodynamic data help determine the safety and clinical considerations necessary when utilizing drugs for plaque psoriasis. A literature search was performed on PubMed and Ovid MEDLINE for the pharmacokinetic and pharmacodynamic data of oral therapies and biologics utilized for moderate-to-severe plaque psoriasis. The findings from the literature search were organized into two sections: oral therapies and biologics. The pharmacokinetic and pharmacodynamic parameters in healthy patients, patients with psoriasis, and special populations are discussed in each section. The oral therapies described in this review include methotrexate, cyclosporine, apremilast, tofacitinib, and deucravacitinib. Biologics include tumor necrosis factor-alpha inhibitors, interleukin-17 inhibitors, ustekinumab, and interleukin-23 inhibitors. Clinical considerations for these therapies include drug toxicities, dosing frequency, and anti-drug antibodies. Methotrexate and cyclosporine have a risk for hepatoxicity and renal impairment, respectively. Moreover, drugs metabolized via cytochrome P450, including tofacitinib and apremilast have decreased clearance in patients with psoriasis, requiring dose adjustments. Patients treated with therapies such as adalimumab can develop anti-drug antibodies that reduce the long-term efficacy of the drug. Additionally, overweight patients benefit from more frequent dosing to achieve better psoriasis clearance.

RISANKIZUMAB DOSE ESCALATION IN PATIENTS WITH CROHN'S DISEASE

Abstract BACKGROUND Patients (pts) who do not achieve optimal response at standard dosing of biologic therapies or lose response over time often benefit from escalated doses of biologic therapies to manage moderate to severe Crohn’s disease (CD). Currently, no data exists on dose escalating risankizumab, an interleukin-23 inhibitor recently approved for the treatment of moderate to severe CD. This cohort study aimed to describe pt characteristics, insurance access, and response to therapy in pts prescribed risankizumab more frequently than the FDA-approved maintenance dosing of 180mg or 360mg every 8 weeks (wks). METHODS We conducted a retrospective single-center cohort study of pts with CD who were initiated on an escalated dose of risankizumab between June 2022 and July 2023. Pts must have received at least one escalated dose during the defined time frame for inclusion. Pt and disease characteristics, steps required to secure insurance access, and early treatment outcomes were collected from the electronic health record and reported descriptively. RESULTS A total of 211 pts completed three standard risankizumab intravenous induction infusions during the study period. Twelve pts were initiated on an escalated maintenance dosing frequency. All 12 pts received the 360mg dose. Seven pts were escalated to a frequency of every 6 wks (58%) and 5 pts were escalated to every 4 wks (42%). Pts were mostly female (67%) with a median age of 42 years (interquartile range [IQR] 30-52). The median number of previous biologic/small molecule drug failures was 4 (IQR 2-5). Eleven (92%) pts previously required a dose escalated biologic, the median years since diagnosis was 15 (IQR 10-17), and median body mass index was 25 kg/m2 (IQR 22-27). Six pts (50%) previously required surgical intervention. Pts received a median of 3 (IQR 2-3) risankizumab injections on standard dosing before a decision to escalate was made. Reasons for escalated dosing included colonoscopy/imaging/pathology results showing inflammation (n=7) or persistent symptoms (n=5). Five (42%) pts were able to access the escalated dose without an additional authorization, 5 (42%) required a prior authorization that was approved, and 2 (17%) required at least one level of appeal or peer to peer review. Through 10/03/2023, 6 pts had a documented improved response to the escalated dosing (50%), 3 remained stable (25%) and 3 had no change (25%) at a median of 88 days (IQR 72-103) from escalation. CONCLUSION This study demonstrated the need for heavily treatment-experienced pts with severe CD to dose escalate risankizumab, often requiring an additional insurance authorization. Most pts improved or remained stable on the escalated dosing, showing promise for risankizumab dose escalation outcomes. More research is needed to assess risankizumab dose escalation long-term outcomes and the role of trough levels.

DOP53 Long-term Efficacy and Safety of Risankizumab in Patients With Moderate to Severe Crohn's Disease up to 3 Years of Treatment: Results From the FORTIFY Open-Label Long-term Extension

Abstract Background The ongoing FORTIFY maintenance open-label extension (OLE) substudy evaluates the long-term efficacy and safety of risankizumab (RZB), a p19 interleukin-23 inhibitor, for treatment of moderate to severe Crohn’s disease (CD). Here, we report 2-year results of FORTIFY OLE. Methods The FORTIFY (NCT03105102) OLE enrolled patients (pts) who completed 52-wks maintenance dosing in the FORTIFY substudies or RZB phase 2 OLE.1,2 All pts received 180 mg subcutaneous (SC) RZB every 8 wks (Q8w), starting at wk56, except for pts who had prior rescue therapy (single 1200mg intravenous [IV] RZB dose then 360mg SC Q8w) who continued 360mg SC Q8w in the OLE. Pts with inadequate response (increased symptoms plus objective marker of inflammation) during the OLE could receive rescue therapy as described above. Pooled data from both treatment groups (RZB 180 mg & 360 mg SC) were assessed. Clinical outcomes were evaluated every 24 wks (endpoint definitions in Figure footnote). Endoscopy was performed every 96 wks. Results are reported as observed. Efficacy data for pts receiving rescue therapy in the OLE were included up to rescue initiation. Safety was assessed through the cutoff date of 05MAR2023. As this trial is ongoing, most patients have not reached the wk152 study visit. Any treatment-emergent adverse events (TEAEs) reported on or after the first dose in the OLE were analysed. Results As of the cutoff date, 1147 pts entered the OLE, of which 203 (17.6%) pts received rescue therapy during the OLE. Clinical response and remission rates were generally maintained with RZB from wks 56 to 152 (CD activity index [CDAI] clinical response, 85.8% to 86.5%, respectively; enhanced clinical response, 88.6% to 89.2%; CDAI clinical remission, 68.5% to 77.6%; stool frequency/abdominal pain score clinical remission, 64.4% to 71.0%) (Figure). At wks 56 and 152, respectively, rates of endoscopic response were 53.4% and 74.2%, endoscopic remission were 37.5%, and 58.9%, and ulcer-free endoscopy were 31.0% and 50.0%. There were no new trends for exposure-adjusted rates of TEAEs, and rates of adjudicated major cardiovascular adverse events, malignancies, serious infections and hepatic events remained stable with no new safety risks identified. There were no events of active tuberculosis, serious hypersensitivity, or adjudicated anaphylactic reaction. Three deaths occurred during the OLE (see Table footnote), all assessed by investigators as unrelated to study drug. Conclusion Pts receiving long-term RZB maintenance therapy in FORTIFY demonstrated sustained clinical and endoscopic efficacy with at least 3 years of treatment. The safety profile is consistent and supports long-term RZB treatment. 1doi: 10.1093/ecco-jcc/jjab093 2doi: 10.1016/S0140-6736(22)00466-4.

Sequential interleukin-17 inhibitors for moderate-to-severe plaque psoriasis who have an IL-17 inhibitors failure in a resource limited country: An economic evaluation.

Biologics has been known to be effective for patients with psoriasis. However, optimal treatment pathways and their cost-effectiveness are limited in a resource-limited country. This study assessed the cost-effectiveness of different sequential biologics for moderate-to-severe plaque psoriasis. A hybrid model from a societal perspective was used. Model inputs were derived from network meta-analysis, clinical trials, and published literature. Three different sequential biologic treatments were assessed; Sequence 1; 1st Interleukin-17 (IL-17) inhibitor (secukinumab) followed by 2nd IL-17 inhibitors (ixekizumab or brodalumab), then 3rd IL-23 inhibitor (guselkumab), Sequence 2; ixekizumab followed by secukinumab or brodalumab, then guselkumab, and Sequence 3; brodalumab followed by ixekizumab or secukinumab, then guselkumab. Methotrexate or ciclosporin was used as standard of care (SoC). All three different sequential biologic therapies could gain total quality-adjusted life year (QALY), but they had higher cost than SoC. Sequence 1 had the lowest incremental cost-effectiveness ratio (ICER) compared to SoC at 621,373 THB/QALY (19,449 $/QALY). ICER for Sequence 2 was 957,258 THB/QALY (29,962 $/QALY), while that for Sequence 3 was 1,332,262 THB/QALY (41,700 $/QALY). Fully incremental analysis indicated that Sequence 3 was dominated by Sequence 1 and Sequence 2. ICER for Sequence 2 was 7,206,104 THB/QALY (225,551 $/QALY) when compared to Sequence 1. At the current willingness-to-pay of 160,000 THB/QALY, no sequential IL-17 inhibitor was cost-effective compared to SoC. Secukinumab followed by ixekizumab or brodalumab then guselkumab (Sequence 1) may be the most appropriate option compared with other treatments.

Evaluating the efficacy of biologics with and without methotrexate in the treatment of psoriatic arthritis: a network meta-analysis

IntroductionAn important consideration in the treatment of patients with psoriatic arthritis (PsA) is whether the addition of methotrexate (MTX) to biologics has greater efficacy than biologic monotherapy with respect to...

Elevating Expectations: Risankizumab’s Impact on Revolutionizing Psoriatic Arthritis Care

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis that is associated with psoriasis (PsO) and affects about 20% of patients with psoriasis. PsA is characterized by a wide range of symptoms that can vary over time, affecting both the musculoskeletal system as well as the skin and nails. The heterogeneity of PsA means that patients might experience fluctuating and diverse manifestations of the disease, requiring a nuanced approach to treatment. In light of this, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) released their 2021 treatment recommendations, which emphasize the importance of individualized therapy based on six specific domains: peripheral arthritis, enthesitis, dactylitis, axial disease, psoriasis, and nail disease. This domain-based approach is designed to address the multifaceted nature of PsA, ensuring that treatment is tailored to the specific clinical manifestations present in each patient. Following this, the European Alliance of Associations for Rheumatology (EULAR) in their 2023 PsA treatment recommendations also adopted a similar approach. They provided strong endorsements for newer therapeutic classes, such as Interleukin-23 inhibitors (IL-23i), particularly in the treatment of peripheral arthritis, significant skin involvement, and enthesitis. Risankizumab stands out as the most recently approved IL-23 inhibitor for the treatment of PsA. Its mechanism of action involves specifically binding to the p19 subunit of IL-23, thereby blocking downstream signaling pathways and suppressing inflammatory responses. Recent analyses have demonstrated Risankizumab’s consistent efficacy across various patient demographics and disease characteristics, making it a versatile and effective option for managing PsA. In this context, Professor Östör will present key trial data and share case experiences with IL-23 inhibitors across the different manifestations of PsA. The aim of this lecture is to enhance the understanding of how to tailor treatment plans according to individual patient preferences and clinical profiles. By delving into these data and case studies, Professor can provide valuable insights into optimizing treatment strategies, ultimately leading to improved patient satisfaction and overall disease control.

Генерализованный пустулезный псориаз и псориатический спондилоартрит: терапевтические опции в реальной клинической практике

Generalized pustular psoriasis (GPP) represents one of the most severe and challenging variants of psoriasis to manage. The global literature primarily documents isolated clinical instances of GPP coexisting with peripheral arthritis, while the occurrence of spondyloarthritis in these patients remains exceedingly rare. This article compiles and analyzes clinical data and treatment guidelines for managing GPP in conjunction with psoriatic spondyloarthritis (PSpA) from various international sources. It also examines recent publications regarding the development, administration, and efficacy of novel targeted therapies. In addition to existing literature, the author shares personal experience in the effective treatment of a GPP patient with concurrent PSpA using a genetically engineered biological drug (GEBD), specifically the interleukin-17 inhibitor netakimab. Administering advanced therapeutic strategies like GEBD is recommended, especially in cases where conventional therapies with basic anti-inflammatory and non-steroidal anti-inflammatory drugs prove ineffective. Owing to the paucity of extensive multicenter studies and absence of GPP registries of patients with PSpA, the formulation of interdisciplinary treatment algorithms remains a critical challenge for both dermatovenerologists and rheumatologists. KEYWORDS: generalized pustular psoriasis, psoriatic spondyloarthritis, psoriasis, genetically engineered biological therapy, interleukin-17 inhibitors, netakimab. FOR CITATION: Vasilenko E.A., Tarasova D.S., Maksimova M.D., Samigullina R.R., Raznatovskiy K.I., Mazurov V.I. Generalized pustular psoriasis and psoriatic spondyloarthritis: therapeutic options in real clinical practice. Russian Medical Inquiry. 2024;8(7):413–420 (in Russ.). DOI: 10.32364/2587-6821-2024-8-7-7.

Does the effectiveness of biological medications in the treatment for psoriasis depend on the moment of starting therapy? A preliminary study.

It is well known that biological medications acting on selected elements of the immune response are highly effective in psoriasis treatment. It is a common perception that psoriasis is a seasonal disorder with improvement in warmer months, however it has not been unequivocally confirmed. It is not known whether the time of year of starting systematic therapy for psoriasis influences treatment outcomes. Changes in psoriasis severity scores during treatment with biologics were investigated. The scores were recorded for 62 patients with moderate to severe psoriasis at the beginning, after 1, 4 and 7 months of the therapy. Patients were divided into two groups: those beginning the treatment in the cold period of the year (November-March) and in the warm period (May-September). The seasonal groups were also divided into subgroups according to the type of biologics used: interleukin inhibitors and tumor necrosis factor α (TNF-α) inhibitors. Results of the treatment were analysed using standard statistical tests of differences between samples. After 1 and 4 months of the therapy, better efficacy of interleukin inhibitors was found in patients starting treatment in summer. The course of psoriasis improvement in patients taking TNF-α inhibitors resulted in consistent improvement regardless of the season. The outcome of the treatment after 7 months was similar for both seasonal groups and types of biologics used. Our understanding of the effectiveness of the treatments depending on the time of the year combined with the type of biologics used, may further improve results of the therapy.