Treatment Of Psoriatic Arthritis Research Articles

Safety and Efficacy of Combination Therapy of Upadacitinib and Biologic Agents for Treatment-Resistant Psoriasis and Psoriatic Arthritis

Importance: Although there are many available treatments for psoriasis and psoriatic arthritis (PsA), there are patients resistant to standard conventional therapy. For these patients, combination therapy of biologic agents and upadacitinib may be a viable alternative option; however, there is limited data on concomitant usage. Objective: To evaluate the safety and efficacy of combination therapy of upadacitinib and biologic agents for the treatment of refractory psoriasis and psoriatic arthritis. Design: We report the results of a retrospective chart review of 3 patients in a single practice treated with a combination of upadacitinib and biologics for psoriasis and PsA. The risks, benefits, and safety warnings of combination therapy of upadacitinib and biologic agents were discussed before initiation. After shared decision-making with the provider, patients were placed on a trial of combination therapy. Results: All three patients, previously refractory to monotherapy, experienced significant improvement of their symptoms while on combination therapy. No adverse reactions (malignancy, cardiovascular events, venous thromboembolism) occurred during treatment. However, one patient experienced a shingles outbreak and diverticulitis while on combination treatment. Further studies are needed to determine long-term efficacy with a larger sample size.

Secukinumab: A Breakthrough in the Treatment of Autoimmune Disease

Secukinumab is a significant advancement in the treatment of autoimmune disease, particularly psoriasis, psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis. By targeting interleukin-17A(IL-17A), it offers a focused approach to mitigating inflammation. This article provides a comprehensive overview of Secukinumab, exploring its mechanism of action, clinical efficacy, safety profile, administration, and ongoing research aimed at expanding its therapeutic scope.

Real-World Treatment Patterns, Clinical Outcomes, and Symptom Burden in Patients With Psoriatic Arthritis Prescribed Ixekizumab in the United States.

The objective of this study was to describe the real-world characteristics and clinical status of patients with psoriatic arthritis (PsA) currently prescribed ixekizumab. Data were drawn from the Adelphi PsA Plus Disease Specific Programme (DSP), a cross-sectional survey conducted in the United States between September 2021 and March 2022. Rheumatologists provided data for their next five consulting patients currently receiving ixekizumab, including demographic and clinical characteristics, disease severity, treatment history, reasons for treatment choice, satisfaction with current treatment, and current and historic symptom burden. Patients voluntarily completed questionnaires, providing perceptional data on symptom burden and satisfaction with current treatment. Overall, 68 rheumatologists provided data on 275 patients with PsA, 90 of whom completed the voluntary questionnaire. Patients had been prescribed ixekizumab for a mean of 11.7 (SD 10.6) months. Clinical characteristics, disease severity, and symptom burden of patients with PsA improved significantly from ixekizumab initiation to the most recent consultation, including symptom burden, tender and swollen joint counts, and body surface area affected by psoriasis (all P < 0.001). Both rheumatologists and patients were satisfied with ixekizumab treatment and reported improvements in pain and fatigue. Improvements were noted after more than three months of ixekizumab treatment duration and regardless of whether the patients had prior exposure to an advanced therapy or were treatment naïve. Our results indicate that ixekizumab was efficacious in the treatment of PsA in real-world clinical practice, complementing efficacy data from randomized controlled clinical trials. The results of this study may assist rheumatologists and their patients in making informed treatment choices.

Bimekizumab: A Review in Psoriatic Arthritis.

Although several biological disease-modifying antirheumatic drugs (bDMARDs), including interleukin (IL)-17A inhibitors, are approved for psoriatic arthritis, the treatment of this disease remains suboptimal. Bimekizumab (Bimzelx®), a dual IL-17A and IL-17F inhibitor, is approved in the EU, Great Britain and Japan for the treatment of psoriatic arthritis. In pivotal phase 3 clinical trials in patients who were bDMARD-naïve or previously had an inadequate response or intolerance to tumour necrosis factor (TNF) α inhibitors, bimekizumab improved the signs and symptoms of psoriatic arthritis across a range of joint, skin, radiographic and patient-reported outcomes compared with placebo, including the proportion of patients achieving a ≥ 50% response in the American College of Rheumatology criteria. Phase 2 clinical trial data have shown that responses are maintained up to 3 years. Bimekizumab was generally well tolerated in patients with psoriatic arthritis, with a safety profile consistent with that in other approved indications. The most common adverse events included nasopharyngitis, upper respiratory tract infection, oral candidiasis, headache and diarrhoea. In conclusion, bimekizumab extends the treatment options available to patients with psoriatic arthritis.

Risk Stratification of Patients with Psoriatic Arthritis and Ankylosing Spondylitis for Treatment with Tofacitinib: A Review of Current Clinical Data.

In this commentary, we review clinical data which helps inform individualized benefit-risk assessment for tofacitinib in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). ORAL Surveillance, a safety trial of patients ≥ 50years of age with rheumatoid arthritis (RA) and cardiovascular risk factors, found increased rates of safety outcomes (including major adverse cardiovascular events [MACE], malignancies excluding non-melanoma skin cancer, and venous thromboembolism) with tofacitinib versus tumor necrosis factor inhibitors (TNFi). Post hoc analyses of ORAL Surveillance have identified subpopulations with different relative risk versus TNFi; higher risk with tofacitinib was confined to patients ≥ 65years of age and/or long-time current/past smokers, and specifically for MACE, patients with a history of atherosclerotic cardiovascular disease (ASCVD). In patients without these risk factors, risk differences between tofacitinib and TNFi could not be detected. Given differences in demographics, pathophysiology, and comorbidities, we sought to examine whether the risk stratification observed in RA is also appropriate for PsA and AS. Data from the PsA tofacitinib development program show low absolute risk of safety outcomes in patients < 65years of age and never smokers, and low MACE risk in patients with no history of ASCVD, consistent with results from ORAL Surveillance. No MACE, malignancies, or venous thromboembolism were reported in the tofacitinib AS development program. The mechanism of the ORAL Surveillance safety findings is unknown, and there are no similar prospective studies of sufficient size and duration. Accordingly, it is appropriate to use a precautionary approach and extrapolate differentiating risk factors identified from ORAL Surveillance (age ≥ 65years, long-time current/past smoking, and history of ASCVD) to PsA and AS. We recommend an individualized approach to treatment decisions based on these readily identifiable risk factors, in line with updated labeling for Janus kinase inhibitors and international guidelines for the treatment of PsA and AS.Trial Registration: NCT02092467, NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT02147587, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02281552, NCT02187055, NCT02831855, NCT00413699, NCT00661661, NCT01877668, NCT01882439, NCT01976364, NCT00678210, NCT01710046, NCT01241591, NCT01186744, NCT01276639, NCT01309737, NCT01163253, NCT01786668, NCT03502616.

The steroid-sparing effect of JAK inhibitors across multiple patient populations.

JAK-inhibitors (JAK-i) represent an effective treatment in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA). Oral glucocorticoids (OGC) are commonly used in combination with JAK-i to reach therapeutic target. We aimed to assess, in a real-life setting, the reduction of OGC dose during JAK-i treatment in active RA and PsA patients. We prospectively enrolled 103 patients (88 RA, 15 PsA) treated with JAK-i: 24% bio-naïve (b-naïve), 76% bDMARD-insufficient responders (bDMARD-IR) and 40% difficult to treat (D2T), defined as failure of ≥2 bDMARDs with different mechanism of action. Disease activity (DAS28 and DAPSA, VAS-pain, GH) and OGC dose was collected at baseline and after 3, 6 and 12 months (T3, T6, T12) of treatment. In all the cohort and in b-naïve patients we reported a reduction of OGC dose at all time-points; bDMARD-IR patients were able to reduce OGC dose at T3 and T12; D2T ones only at T3. We reported an improvement of disease activity and withdrawal of OGC as early as three months of therapy, at all time-points, regardless of line of bDMARD treatment. Chronic OGC may cause detrimental bone, metabolic, cardiovascular side effects and infections; therefore JAK-i steroid-sparing effect may be beneficial for patients in long-term treatment.

Effectiveness of risankizumab for the treatment of psoriatic arthritis: a multicenter, real-world study.

IL-23 inhibitors were recently approved for the treatment of skin psoriasis and psoriatic arthritis (PsA). Risankizumab, a humanized monoclonal antibody that specifically binds the p19 subunit of IL-23, has proven effective on PsA in two randomized controlled trials. To date, only a few real-world data are available on this topic. Our study aimed to prospectively evaluate the effectiveness of risankizumab in patients with PsA in a real-world setting. For this purpose, both rheumatologic and dermatologic assessments were performed at baseline and after 28-40 weeks of continuous risankizumab administration. Moreover, joint and entheses ultrasound assessment was performed at the mentioned time points. The rheumatologic assessment was carried out by means of the following scores: (i) clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA); (ii) Leeds Enthesitis Index (LEI); (iii) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and (iii) Bath Ankylosing Spondylitis Functional Index (BASFI). The degree of skin involvement was measured by both the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Quality of life was assessed by the Health Assessment Questionnaire (HAQ) and Dermatology Life Quality Index (DLQI). Ultrasound assessment of joints and entheses was performed on the basis of the EULAR-OMERACT score. After treatment, cDAPSA decreased from a mean value of 12.9 ± 7.6 to 7.0 ± 6.1 (P < 0.001), and the median PD score significantly decreased from baseline (3; range 1-8) to TP1 (1; range 0-7) (P < 0.001). PASI score also decreased from 8.4 ± 4.9 to 0.3 ± 0.5 (P < 0.001), and PGA from 3.1 ± 1.0 to 0.4 ± 0.5 (P < 0.001). We can conclude that risankizumab led to substantial improvement in both skin and joint involvement.

Chemical profiling and in-silico prediction of bioactive compounds from Wrightia tinctoria R.Br to treat psoriatic arthritis

Psoriatic arthritis (PsA) is an autoimmune-mediated inflammatory skin condition with limited remedies. This study mainly focuses on exploring the therapeutic efficiencies of Wrightia tinctoria R.Br (WT) for the treatment of PsA. Quantification and chemical profiling for the WT leaves were tested using standard in vitro biochemical assays. The ethanol extract of WT has been found to have high amounts of phenolic (24.48±0.03 mg/mL) and flavonoid (29.2±0.16 mg/mL) contents when compared to other solvent fractions. We also conducted a series of in vitro assays, including DPPH, nitric oxide radical scavenging, and protein denaturation inhibition assays, to assess the overall antioxidant and anti-inflammatory capabilities of WT extracts. The GC-MS analysis of WT leaf extract displayed Lup-20(29)-en-3-yl acetate, 24-Norursa-3,12-diene, and 3-O-Methyl-D-fructose as major bioactive compounds. The screened bioactive compounds, via pharmacokinetic and pharmacodynamic analysis, were subjected to density functional theory for energy minimization. Further, the hub targets of PsA were filtered from the Open Target online database to study the drug-target interaction. CD4, CXCL12, KLRD1, MMP9, and SERPINA1 were found to be the primary targets, which have a central role in the disease pathway. Selected disease targets were then docked with the energy-minimized bioactive compounds from WT leaves using PyRx. The results suggest that the ethanolic leaf extract from WT leaves could alter the progression of pathway mediators and effectively manage the PsA.

Pan American League of Associations for Rheumatology Recommendations for the Treatment of Psoriatic Arthritis.

Psoriatic arthritis (PsA) is chronic disease that compromises multiple domains and might be associated with progressive joint damage, increased mortality, functional limitation, and considerably impaired quality of life. Our objective was to generate evidence-based recommendations on the management of PsA in Pan American League of Associations for Rheumatology (PANLAR) countries. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach to adapt the 2019 recommendations of the European Alliance of Associations for Rheumatology. A working group consisting of rheumatologists from various countries in Latin America identified relevant topics for the treatment of PsA in the region. The methodology team updated the evidence and synthesized the information used to generate the final recommendations. These were then discussed and defined by a panel of 31 rheumatologists from 15 countries. Theses guidelines report 15 recommendations addressing therapeutic targets, use of antiinflammatory agents and corticosteroids, treatment with disease-modifying antirheumatic drugs (conventional synthetic, biologic, and targeted synthetic), therapeutic failure, optimization of biologic therapy, nonpharmacological interventions, assessment tools, and follow-up of patients with PsA. Here we present a set of recommendations to guide decision making in the treatment of PsA in Latin America, based on the best evidence available, considering resources, medical expertise, and the patient's values and preferences. The successful implementation of these recommendations should be based on clinical practice conditions, healthcare settings in each country, and a tailored evaluation of patients.

Efficacy and safety of tofacitinib for chronic plaque psoriasis and psoriatic arthritis: a systematic review and meta-analysis of randomized controlled trials.

To summarize and analyze the results of published randomized controlled trials of tofacitinib for the treatment of chronic plaque psoriasis and psoriatic arthritis(PsA) and discuss its efficacy and safety. An exhaustive systematic search encompassing PubMed, Cochrane, Embase, and Web of Science databases was conducted up to July 2023. Studies eligible for inclusion were analyzed, organized using Review Manager version 5.4.1 (Cochrane Collaboration, Oxford, UK) and STATA 15.0 version (Stata Corp, College Station, TX, USA) software. A total of six articles, covering 1393 patients (844 treated with tofacitinib and 549 with placebo), were included. The foundational characteristics of tofacitinib and placebo group showed similarity, except for age and Dermatology Life Quality Index (DLQI) score, especially in the context of chronic plaque psoriasis. It is noteworthy that we discovered tofacitinib exhibited a significant impact on Psoriasis Area and Severity Index 75 (PASI75) response, Physician's Global Assessment (PGA) response, and adverse events (AEs) in cases of chronic plaque psoriasis. Similarly, tofacitinib demonstrated substantial influence on American College of Rheumatology 20/50 (ACR20/50) response, PASI75 response, as well as alterations in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score, Health Assessment Questionnaire-Disability Index (HAQ-DI) Score, Dactylitis Severity Score (DSS), and Leeds Enthesitis Index (LEI) Score in the context of psoriatic arthritis (PsA). Nevertheless, there was no statistically significant impact of tofacitinib on serious adverse events (SAEs) in chronic plaque psoriasis, as well as on both adverse events (AEs) and SAEs in psoriatic arthritis (PsA). A comprehensive analysis revealed that tofacitinib has a positive effect on addressing skin and joint symptoms, as well as improving the quality of life for patients with chronic plaque psoriasis and psoriatic arthritis (PsA). However, the safety of the drug's long-term usage even requires further validation. Key Points • In 6 analyses involving a total of 1393 patients, tofacitinib exhibits positive effect on the treatment of both chronic plaque psoriasis and psoriatic arthritis (PsA). • Although dose-based subgroup analyses have demonstrated effectiveness. Some studies indicate that the 5-mg dose (twice daily) may not show an effect due to the failure of non-inferiority trials comparing tofacitinib with placebo. Therefore, caution is required when interpreting its effectiveness. On the other hand, the 10-mg dose (BID) has been associated with an increase in adverse events and serious adverse events,and is recommended to be used with caution in patients with cardiovascular or uveitis risk factors. • Tofacitinib has efficacy in comorbid psychiatric disorders (depression, anxiety, or Alzheimer's disease) and inflammatory bowel disease (ulcerative colitis), but patients with comorbid renal insufficiency, hepatic dysfunction, osteoporosis, cardiovascular disease, or uveitis may need to be moderated or avoided with tofacitinib.

Effectiveness and safety of biological and target synthetic drugs treatment for psoriatic arthritis: a systematic review with network meta-analysis

BackgroundPsoriatic arthritis (PA) is a chronic inflammatory systemic arthritis that can result in loss of functional capacity and joint deformation. This systematic review assessed the effectiveness and safety of biological and target synthetic drugs for treating PA.MethodsWe searched for randomized clinical trials (RCTs) that evaluated the use of Adalimumab, Etanercept, Infliximab, Golimumab, Secukinumab, Certolizumab Pegol and Tofacitinib in the main general databases and clinical trial registers databases. The primary outcomes were ACR 50, PsARC, and serious adverse events. Two independent reviewers performed study selection and data extraction. Network meta-analyses were conducted using a random effects model and frequentist approach. The CINeMA software was used to assess the certainty of evidence.ResultsWe included 33 RCTs (n = 11,034). The results from the network meta-analysis for the ACR 50 at 6-months follow-up showed that all drugs were superior to placebo, with Secukinumab (high certainty of evidence), Infliximab (very low certainty of evidence) and Adalimumab (high certainty of evidence) ranking the highest. Regarding the PsARC (at 6-months follow-up), all drugs, except for Golimumab (very low certainty of evidence), were superior to placebo, with Etanercept (low certainty of evidence), Infliximab (low certainty of evidence) and Certolizumab Pegol (low certainty of evidence) being the most effective drugs. There were no significant differences in the risk of serious adverse events between the drugs and placebo. Golimumab (very low certainty of evidence), Secukinumab (low certainty of evidence), and Adalimumab (very low certainty of evidence) ranked the highest for safety.ConclusionsIn conclusion, based on the balance between efficacy and safety, Secukinumab and Adalimumab may be the preferred options among the evaluated drugs for treating patients with PsA. However, caution is necessary when interpreting the safety findings, as they are supported by evidence of low to very low certainty. Consequently, the balance between benefits and potential risks may change as new safety evaluation studies become available.Protocol registrationPROSPERO: CRD42022315577

Efficacy and safety of pharmacological treatment of psoriatic arthritis: a systematic literature research informing the 2023 update of the EULAR recommendations for the management of psoriatic arthritis

ObjectivesTo obtain an overview of recent evidence on efficacy and safety of pharmacological treatments in psoriatic arthritis (PsA).MethodsThis systematic literature research (SLR) investigated the efficacy and safety of conventional synthetic...

Early Oligoarticular Psoriatic Arthritis Responds to Treatment With Apremilast: Week 16 Results From FOREMOST - a Phase 4 Randomized Controlled Trial

Early Oligoarticular Psoriatic Arthritis Responds to Treatment With Apremilast: Week 16 Results From FOREMOST – a Phase 4 Randomized Controlled Trial&#x0D; Laure Gossec1, Dafna Gladman2, Laura C. Coates3, Jacob Aelion4, Jitendra Vasandani5, Jyotsna Reddy6, Rebecca Wang6, Michele Brunori6, Stephen Colgan6, Philip Mease7&#x0D; 1Sorbonne Université and Pitié Salpêtrière Hospital, Paris, France; 2Toronto Western Hospital, Toronto, ON, Canada; 3University of Oxford, Oxford, UK; 4West Tennessee Research Institute, Jackson, TN, USA; 5West Texas Clinical Research, Lubbock, TX, USA; 6Amgen Inc., Thousand Oaks, CA, USA; 7Swedish Medical Center/Providence St. Joseph Health and University of Washington School of Medicine, Seattle, WA, USA&#x0D; Introduction &amp; Objectives:&#x0D; Psoriatic arthritis (PsA) is underdiagnosed in dermatology practice, typically presenting 10 years after skin symptoms. Dermatologists may encounter early PsA since up to 30% of patients with psoriasis have PsA. Oligoarticular PsA affects ≤4 joints, is very common, and is underrepresented in clinical trials as most pivotal studies exclude patients with &lt;3 swollen and tender joints. Here, we report the efficacy and safety of apremilast vs. placebo for the treatment of early oligoarticular PsA.&#x0D; Materials &amp; Methods:&#x0D; FOREMOST (NCT03747939) is a phase 4, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Patients with PsA,based on CAPSAR criteria, duration ≤5 years, swollen joint count (SJC) &gt;1 but ≤4, and tender joint count (TJC) &gt;1 but ≤4 were randomized 2:1 to apremilast 30 mg BID (APR) or placebo for 24 weeks. The primary endpoint was the achievement of minimal disease activity (MDA)-Joints1 (mandating SJC ≤1 and TJC ≤1, and 3/5 alternate items) at week 16.&#x0D; Results:&#x0D; Of 308 patients randomized (APR: n=203; placebo: n=105), mean PsA duration was 9.9 months, mean age was 50.9 years, and 39.9% of patients were using csDMARD. MDA-Joints response was achieved in 33.9% vs. 16.0% for patients treated with APR vs. placebo (primary endpoint, P=0.0008). At week 16, a significantly greater proportion, 70.2%, of patients treated with APR achieved cDAPSA REM/LDA vs. 51.8% with placebo (P=0.0017). A greater proportion of patients achieved a good/moderate response in PASDAS score with APR (59.9%) vs. placebo (42.7%). Greater improvements from baseline in PsA Impact of Disease (PsAID)-12 score (LS mean change, −1.5 vs. −0.4; nominal P&lt;0.0001) and nail psoriasis score (visual analog scale [VAS]; LS mean change, −13.9 vs. −6.8; nominal P=0.0094) were observed with APR vs. placebo at week 16. Patients treated with APR also achieved greater improvement in quality of life measures (Patient Pain [VAS ≤15: 59.6 vs. 13.8; nominal P=0.0022], Patient Global Assessment [PtGA; VAS ≤20: 61.7 vs. 20.1; nominal P=0.0286]) when compared to placebo at week 16. No new safety signals were identified.&#x0D; Conclusion:&#x0D; FOREMOST is the first global randomized controlled trial exclusively studying early oligoarticular PsA. We report the first results of FOREMOST, the primary outcome, and show better disease control is achievable with APR, with twice the MDA-Joint response compared with placebo at 16 weeks. These findings show APR treatment of early oligoarticular PsA improves clinical and quality of life outcomes and may inform optimal management of these patients.&#x0D; Reference: 1. Coates LC, et al. J Rheumatol. 2016;43:371–5.

PDE4 Gene Family Variants Are Associated with Response to Apremilast Treatment in Psoriasis.

Moderate-to-severe psoriasis (Ps) treatment includes systemic drugs and biological agents. Apremilast, a small molecule primarily metabolized by cytochrome CYP3A4, modulates the immune system by specifically inhibiting phosphodiesterase type 4 (PDE4) isoforms and is currently used for the treatment of Ps and psoriatic arthritis (PsA). Clinical trials and real-world data showed variable efficacy in response among Ps patients underlying the need for personalized therapy. This study implements a candidate-gene and a network-based approach to identify genetic markers associated with apremilast response in forty-nine Greek Ps patients. Our data revealed an association of sixty-four SNPs within or near PDE4 and CYP3A4 genes, four SNPs in ncRNAs ANRIL, LINC00941 and miR4706, which influence the abundance or function of PDE4s, and thirty-three SNPs within fourteen genes whose protein products either interact directly with PDE4 proteins or constitute components of the cAMP signaling pathway which is modulated by PDE4s. Notably, fifty-six of the aforementioned SNPs constitute eQTLs for the respective genes in relevant to psoriasis tissues/cells implying that these variants could be causal. Our analysis provides a number of novel genetic variants that, upon validation in larger cohorts, could be utilized as predictive markers regarding the response of Ps patients to apremilast treatment.

TYK2: an emerging therapeutic target in rheumatic disease.

Tyrosine kinase 2 (TYK2) is a member of the JAK kinase family of intracellular signalling molecules. By participating in signalling pathways downstream of type I interferons, IL-12, IL-23 and IL-10, TYK2 elicits a distinct set of immune events to JAK1, JAK2 and JAK3. TYK2 polymorphisms have been associated with susceptibility to various rheumatic diseases including systemic lupus erythematosus and dermatomyositis. In vitro and animal studies substantiate these findings, highlighting a role for TYK2 in diseases currently managed by antagonists of cytokines that signal through TYK2. Various inhibitors of TYK2 have now been studied in human disease, and one of these inhibitors, deucravacitinib, has now been approved for the treatment of psoriasis. Phase II trials of deucravacitinib have also reported positive results in the treatment of psoriatic arthritis and systemic lupus erythematosus, with a preliminary safety profile that seems to differ from that of the JAK1, JAK2 and JAK3 inhibitors. Two other inhibitors of TYK2, brepocitinib and ropsacitinib, are also in earlier stages of clinical trials. Overall, TYK2 inhibitors hold promise for the treatment of a distinct spectrum of autoimmune diseases and could potentially have a safety profile that differs from other JAK inhibitors.

Real-world evaluation of persistence, effectiveness and usage patterns of tofacitinib in treatment of psoriatic arthritis in Australia

ObjectivesTo describe treatment patterns and persistence of tofacitinib, interleukin 17 inhibitors (IL-17Ai) and tumour necrosis factor inhibitors (TNFi), in patients with psoriatic arthritis (PsA).MethodsData from adult patients with PsA and who had received at least one prescription of tofacitinib, IL-17Ai or TNFi between May 2019 and September 2021 were sourced from the Australian OPAL dataset. Persistence, analysed via Kaplan–Meier methods, and propensity score matching between tofacitinib and bDMARD (IL-17Ai and TNFi) groups were conducted.ResultsOf 16,692 patients with PsA, 1486 (n = 406 tofacitinib, n = 416 IL-17Ai and n = 664 TNFi) were included. More females were in the tofacitinib group (75.4%) than in the IL-17Ai (61.1%) and TNFi (64.8%) groups. Overall, 19.2% of tofacitinib patients were first line, compared with 41.8% of IL-17Ai and 62.8% of TNFi patients. In the overall population, the median persistence was 16.5 months (95% CI 13.8 to 19.5 months), 17.7 months (95% CI 15.8 to 19.6 months) and 17.2 months (95% CI 14.9 to 20.5 months) in the tofacitinib, IL-17Ai and TNFi groups, respectively. Persistence was similar in the tofacitinib/IL-17Ai matched population; however, in the tofacitinib/TNFi matched population, persistence was longer in the tofacitinib group (18.7 months, 95% CI 15.6 to 21.4 months) compared with the TNFi group (12.2 months, 95% CI 19.9 to 14.9 months).ConclusionsIn this Australian real-world dataset, tofacitinib was more frequently used in later lines and among a slightly higher proportion of female patients than IL-17Ai or TNFi. Overall, treatment persistence was similar for tofacitinib, IL-17Ai and TNFi, but tofacitinib exhibited longer persistence than TNFi in a matched population.Key Points• This is the first, large real-world study from Australia investigating the demographics, treatment patterns and comparative treatment persistence of patients with psoriatic arthritis (PsA) treated with tofacitinib and biologic disease-modifying drugs (bDMARDs).• The study suggests that tofacitinib is an effective intervention in PsA with at least comparable persistence to bDMARDs: tumour necrosis factor inhibitors (TNFi) and interleukin-17 A inhibitors (IL-17Ai).

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.

Comparative Effectiveness of Bimekizumab and Secukinumab in Patients with Psoriatic Arthritis at 52Weeks Using a Matching-Adjusted Indirect Comparison.

Matching-adjusted indirect comparisons (MAICs) were used to compare the efficacy of bimekizumab and secukinumab 150mg and 300mg at 52weeks for the treatment of psoriatic arthritis (PsA) in patients who were biologic disease-modifying anti-rheumatic drug-naïve (bDMARD-naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR). Relevant trials were systematically identified. Individual patient data from bimekizumab randomized controlled trials, BE OPTIMAL (N = 431) and BE COMPLETE (N = 267), were matched to aggregate data from bDMARD-naïve and TNFi-IR patient subgroups from FUTURE2 using secukinumab 150mg and 300mg doses (bDMARD-naïve: N = 63/37; TNFi-IR: N = 67/33). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted using propensity scores to match the baseline characteristics of patients in the secukinumab trials. Unanchored comparisons of recalculated bimekizumab and secukinumab 52-week non-responder imputation outcomes for 20/50/70% improvement in American College of Rheumatology score (ACR20/50/70) and minimal disease activity (MDA) index were analyzed. In patients who were bDMARD-naïve, bimekizumab had a greater likelihood of ACR70 response than secukinumab 150mg (odds ratio [95% confidence interval] 2.39 [1.26, 4.53]; p = 0.008) and secukinumab 300mg (2.03 [1.11, 3.72]; p = 0.021) at 52weeks. In patients who were TNFi-IR, bimekizumab had a greater likelihood of response compared to secukinumab 150mg for ACR20 (3.50 [1.64-7.49]; p = 0.001), ACR50 (3.32 [1.41, 7.80]; p = 0.006), ACR70 (2.95 [1.08, 8.07]; p = 0.035) and MDA (3.52 [1.38, 8.99]; p = 0.009), and a greater likelihood of response compared to secukinumab 300mg for ACR50 (2.44 [1.06, 5.65]; p = 0.037) and MDA (2.92 [1.20, 7.09]; p = 0.018) at 52weeks. In this MAIC analysis, the efficacy of bimekizumab, as demonstrated by the likelihood of ACR20/50/70 and MDA response at 52weeks, was greater or comparable to secukinumab 150mg and 300mg for patients with PsA who were bDMARD-naïve and TNFi-IR. NCT03895203, NCT03896581, NCT04009499, NCT01752634, NCT01989468, NCT02294227, NCT02404350.

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.

Comparing Efficacy of Guselkumab versus Ustekinumab in Patients with Psoriatic Arthritis: An Adjusted Comparison Using Individual Patient Data from the DISCOVER and PSUMMIT Trials.

Two biologic therapies for psoriatic arthritis (PsA), guselkumab and ustekinumab, have demonstrated superior efficacy versus placebo in clinical trials. However, no head-to-head studies have been conducted comparing these two treatments for PsA. The objective was to indirectly compare guselkumab and ustekinumab on joint and skin efficacy up to week 52, using pooled individual patient-level data (IPD) from PsA trials. IPD, including baseline characteristics, American College of Rheumatology (ACR) scores and Psoriasis Area Severity Index (PASI) response from guselkumab (DISCOVER-1 and -2) and ustekinumab (PSUMMIT 1 and 2) trials were pooled. Differences in patient characteristics across trials were adjusted using multivariate logistic regression. Odds ratios (OR) were used to derive absolute response probabilities in the guselkumab trial population and were presented with 95% confidence intervals. Most baseline characteristics for guselkumab-treated patients (100 mg every 8 weeks [Q8W]; 100 mg every 4 weeks [Q4W]) were comparable to ustekinumab-treated patients (45/90 mg). In biologic-naïve patients, both guselkumab doses showed significantly higher ACR 20 (Q8W: 1.97; 1.37, 2.84; Q4W: 2.04; 1.40, 2.96) and PASI 90 (Q8W: 2.33; 1.52, 3.56; Q4W: 2.57; 1.67, 3.97) versus ustekinumab from week 16 onwards. In biologic-experienced patients, both guselkumab doses showed significantly higher ACR 20 (Q8W: 2.57; 1.11, 5.93; Q4W: 2.63; 1.12, 6.17) versus ustekinumab from week 24 onwards; for PASI 90, both guselkumab doses were superior to ustekinumab at week 16 and 52 (Q8W: 3.96; 1.39, 11.27; Q4W: 13.10; 4.18, 41.04). Guselkumab efficacy was similar and robust across primary, scenario, and sensitivity analyses. IPD analysis demonstrated that both guselkumab doses were superior to ustekinumab for ACR 20 from weeks 16 (biologic-naïve) and 24 (biologic-experienced) onwards, and for PASI 90 at weeks 16 and 52 for both subgroups.