Adalimumab For Psoriasis Research Articles

NLRP3 (rs10754558) gene polymorphism and tumor necrosis factor alpha as predictors for disease activity and response to methotrexate and adalimumab in psoriasis

BackgroundPsoriasis has a global prevalence of 1–3%, with variations observed across different ethnic groups and geographical areas. Disease susceptibility and response to anti-tumor necrosis factor-α (TNFα) drugs suggest different genetic regulatory mechanisms which may include NLR family pyrin domain containing 3 (NLRP3) polymorphism. Evaluation of the NLRP3 gene polymorphism, the serum level of CRP and TNFα in psoriasis patients and assessment of the NLRP3 (rs10754558) gene polymorphism, CRP and TNFα with disease severity and their role as biomarkers for response to Methotrexate and Adalimumab in psoriasis. The study had a total of 75 patients diagnosed with psoriasis vulgaris, who were compared to a control group of 75 healthy individuals.ResultsThere was a highly significant difference in NLRP3 genotypes and alleles distribution between psoriasis patients and controls (P = 0.002,0.004). The heterozygote genotype GC (OR = 3.67,95%CI:1.75–7.68, P = 0.0006), was linked with increased risk of psoriasis. Additionally, The GC genotype was significantly associated with nonresponse to psoriasis therapy (OR = 11.7,95%CI:3.24–42.28, P = 0.0002). Regarding serum CRP and TNFα levels, there was a highly statistically significant difference between psoriasis patients and controls (P < 0.0001), and there was also a highly statistically significant difference between responders and non-responders in psoriasis patients regarding PASI 50 (P < 0.0001).ConclusionsThe NLRP3 (rs10754558) genotypes GC was associated with the severe form of psoriasis and with nonresponse to psoriasis medication. Therefore, NLRP3 (rs10754558) gene polymorphism is an important prognostic biomarker in psoriasis patients. The serum TNFα can be used as a predictor for response to therapy in psoriasis patients. More research for evaluation of role of the NLRP3 gene polymorphism in the genetic risks and treatment outcomes associated with psoriasis is still required.

Lupus-Like Syndrome in a Patient Treated With Adalimumab for Psoriasis.

Lupus-Like Syndrome in a Patient Treated With Adalimumab for Psoriasis.

Rituximab as possible therapy in TNF inhibitor-induced IgA vasculitis with severe renal involvement

BackgroundWe observe the increasing use of tumor necrosis factor (TNF) inhibitors in patients affected by chronic inflammatory diseases. These drugs provide good control of symptoms, contributing to significant improvement in the quality of life in individuals with high disease burden. On the other hand, along with their wider use and longer follow-up periods the number of reports regarding their adverse effects is also increasing. The reported complications include drug-induced vasculitis with possible kidney involvement. In the literature we can distinguish more frequently described ANCA-associated vasculitis and more rarely occurring immunoglobulin A vasculitis. Although uncommon, such complications may present with potentially life-threatening vital organ dysfunction; therefore, adequate monitoring and effective therapy are necessary.Case presentationWe report two cases of TNF inhibitor-induced vasculitis with severe acute worsening of renal function and significant proteinuria. The first patient was receiving golimumab therapy for ankylosing spondylitis and the second patient was treated with adalimumab for psoriasis and psoriatic arthritis. In the second case dialysis treatment was necessary and the patient presented recurrence of vasculitis after rechallenge with adalimumab. Both patients underwent renal biopsy which showed findings compatible with drug-induced IgA vasculitis and both were treated successfully with corticosteroids and rituximab.ConclusionsTo the best of our knowledge this is the first report of rituximab use in drug-induced IgA vasculitis with renal involvement. Combination of corticosteroids and rituximab can be an effective therapy in case of vasculitis with kidney failure and a preferable option for selected patients with drug-induced IgA vasculitis compared to cyclophosphamide. More studies are necessary to establish suitable short- and long-term treatment. Given the rarity of this disorder, case reports and case series can provide practical guidance until additional studies become available.

Comparison of Survival and Retention Rates between Infliximab and Adalimumab for Psoriasis: 10-Year Experience at a Single Tertiary Center

Background: Ten-year survival and retention rate data on biologics are extremely limited, and there is a need to evaluate these metrics based on real-world data as well as on the results of clinical studies. Objective: The objective of this study was to assess the long-term survival rates of adalimumab and infliximab in real-life practice. Methods: This study is based on data from the Turkish Psoriasis Registry and the digital records of the Medical School of Bezmialem Vakif University. Baseline data including demographic characteristics, duration of treatment, use of combination treatments, modified regimens, and reasons for treatment termination were extracted. Results: In total, 404 patients (228 on adalimumab and 176 on infliximab) treated between July 1, 2005, and December 31, 2020, were identified. The retention rate was 7.4% for infliximab and 3.5% for adalimumab after 10 years (p = 0.85). Conclusions: The efficacy of infliximab and adalimumab diminishes over time. There were no significant differences in the retention rate between the two drugs, but the survival time was longer for infliximab according to Kaplan-Meier analysis.

Koebner’s phenomena observed in patient receiving adalimumab in psoriasis

Koebner’s phenomena, first described in 1877 as the appearance of psoriatic lesions in the uninvolved skin of psoriatic patients as a consequence of trauma. Koebner phenomena has been associated with the use of biological response modifiers. The development of the anti-TNF therapies is a milestone in the therapy of rheumatic diseases. As in all new treatment opportunities it is of concern whether all potential undesired side effects have been evaluated. We report a case involving a 31-year-old young male patient diagnosed with psoriasis and psoriatic arthritis (PsA) since a year, who received Adalimumab as part of his treatment and developed Koebner’s phenomena.

Effectiveness and safety of Adalimumab in psoriasis and its influence on gut microbiome

Psoriasis is an inflammatory immune-mediated skin disease that significantly impacts physical and psychological well-being. Adalimumab (ADA), a tumor necrosis factor (TNF)-α antagonist, is used to treat psoriasis. This study was performed to assess the efficacy and safety of ADA, identify the fecal microbial composition of psoriasis patients, and explore the effect of ADA on the gut bacteria in psoriasis. Clinical characteristics of the 13 psoriasis patients before (BT) and after ADA treatment (AT) were collected. And total 39 fecal samples from 13 psoriasis patients (BT and AT) and 13 healthy controls were sequenced by 16S rRNA and analyzed by informatics methods. After three months’ ADA treatment, physician global assessment (PGA), psoriasis area and severity index (PASI), dermatology life quality index (DLQI), state-trait anxiety inventory (STAI), and itch numeric rating scale (NRS) scores all decreased, and there were no severe adverse effects. Besides, the microbiota of the psoriasis group differed from that of the healthy group, but no microbial diversity and composition alteration were observed between psoriasis patients BT and AT. We suggested that the gut microbiome may change more slowly than skin lesions. Long-term follow-up of patients treated with ADA and further study of psoriasis based on microbiota may provide more evidence for the treatment of psoriasis.

045 NF-κB phosphorylation in type-2 dendritic cells at baseline is a blood predictive biomarker of clinical response to adalimumab in psoriasis

Biological therapies have transformed the management of psoriasis, but clinical response is variable and there is an unmet clinical need to identify predictive biomarkers. Whilst newer biologics have been licensed, the anti-TNF drug adalimumab remains a first-line intervention in psoriasis, given its effectiveness, well-established safety profile and, with the advent of biosimilars, significantly reduced costs. Nevertheless, the cellular and molecular mechanisms underpinning its clinical efficacy are ill understood and no companion diagnostic exists to guide prescription.

Enhanced NF-\u03baB signaling in type-2 dendritic cells at baseline predicts non-response to adalimumab in psoriasis

Biologic therapies have transformed the management of psoriasis, but clinical outcome is variable leaving an unmet clinical need for predictive biomarkers of response. Here we perform in-depth immunomonitoring of blood immune cells of 67 patients with psoriasis, before and during therapy with the anti-TNF drug adalimumab, to identify immune mediators of clinical response and evaluate their predictive value. Enhanced NF-κBp65 phosphorylation, induced by TNF and LPS in type-2 dendritic cells (DC) before therapy, significantly correlates with lack of clinical response after 12 weeks of treatment. The heightened NF-κB activation is linked to increased DC maturation in vitro and frequency of IL-17+ T cells in the blood of non-responders before therapy. Moreover, lesional skin of non-responders contains higher numbers of dermal DC expressing the maturation marker CD83 and producing IL-23, and increased numbers of IL-17+ T cells. Finally, we identify and clinically validate LPS-induced NF-κBp65 phosphorylation before therapy as a predictive biomarker of non-response to adalimumab, with 100% sensitivity and 90.1% specificity in an independent cohort. Our study uncovers important molecular and cellular mediators underpinning adalimumab mechanisms of action in psoriasis and we propose a blood biomarker for predicting clinical outcome.

An Update Review of Biosimilars of Adalimumab in Psoriasis – Bioequivalence and Interchangeability

Biologic drugs have revolutionized the treatment of psoriasis and other rheumatological diseases. In recent years, many biosimilar agents that are highly similar in structure and function to their originator products have been developed, including the tumor necrosis factor-alpha antagonist adalimumab. The considerably lower cost of these products has greatly cut the economic burden of the patients and increased the accessibility of biologic therapies worldwide. The US Food and Drug Administration and/or the European Medicines Agency have approved eight biosimilars of adalimumab (ABP 501/BI 695501/SB5/GP2017/FKB327/MSB11022/PF-06410293/CT-P17) for the treatment of psoriasis, and others are under review. Given that these agents showed pharmacokinetic, efficacy, safety, and immunogenicity profiles comparable to those of the originator, adalimumab biosimilars were licensed for all indications approved for reference adalimumab based on extrapolation; however, some of the equivalence studies were only conducted in one or two disease populations. This review discusses the bioequivalence of adalimumab biosimilars as demonstrated by various clinical trials, the extrapolation of indications, guidance and policies of the EU and US on interchangeability (nonmedical switching/automatic substitution) between biosimilars and originators, and the real-life practices of switching from reference adalimumab to the respective biosimilars. Further data from real-world studies and post-marketing analyses are needed better to address the efficacy and safety of the transition strategy.

P69: Implementing therapeutic drug monitoring of adalimumab in psoriasis: from theory to practice

P69: Implementing therapeutic drug monitoring of adalimumab in psoriasis: from theory to practice

Erythematous plaques with zosteriform distribution in a patient treated with TNF-α inhibitor adalimumab for psoriasis.

Erythematous plaques with zosteriform distribution in a patient treated with TNF-α inhibitor adalimumab for psoriasis.

Long-term safety and efficacy of adalimumab in psoriasis: a multicentric study focused on infections (connecting study).

IntroductionThis Italian multicenter retrospective study evaluated safety and efficacy of the anti-TNF drug, adalimumab, in a cohort of patients affected by tuberculosis (TB), hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV). Psoriasis is an autoimmune disease affecting around 3% of the Italian population and associated with several comorbidities, including arthritis, cardio-metabolic diseases and depression. In its moderate-to-severe form, psoriasis profoundly impairs quality of life of patients.AimTherefore, these patients deserve systemic treatments including conventional DMARDS (disease modifying anti-rheumatic drugs) and biologics. Management of moderate and severe psoriasis patients affected by relevant infections such as TB, HBV, HCV and HIV may be difficult because of the toxicity of the conventional systemic treatment.Material and methodsThe CONNECTING study analysed 28 moderate to severe psoriasis patients infected by TB, HBV, HCV and HIV who were treated with adalimumab for up to 96 weeks together with respective prophylactic treatment.ResultsWe observed a rapid decrease in PASI (psoriasis area severity index) reaching a 75% improvement in 91% of patients. Some of these patients (n = 9) were also affected by arthritic comorbidity. The patients experienced a rapid decrease in pain, measured by pain VAS (visual analogic scale) that reached 0 in all of them. Monitoring of the respective infection did not show any worsening or reactivation of infection or any severe adverse events during the entire observation period.ConclusionsAdalimumab is effective and safe in patients affected by these important infections.

399 Distinct gene expression signatures differentiate clinical response to ustekinumab compared to adalimumab in psoriasis

399 Distinct gene expression signatures differentiate clinical response to ustekinumab compared to adalimumab in psoriasis

Dose Tapering Study of Adalimumab in Psoriasis

Dose Tapering Study of Adalimumab in Psoriasis

Adalimumab in Psoriasis: How Much Is Enough?

Biologic therapies targeting tumor necrosis factor have revolutionized treatment of immune-mediated inflammatory diseases such as psoriasis, but optimal dosing and appropriate use of therapeutic drug monitoring are not yet fully understood. Wilkinson etal. explore these questions in a real-world psoriasis cohort on adalimumab monotherapy, defining a therapeutic range and finding value in early measurement for predicting clinical response.

Real-life 9-year experience with adalimumab in psoriasis and psoriatic arthritis: results of a single-centre, retrospective study.

Observational studies in daily practice are an essential complement to pivotal randomised controlled trials because their findings refer to larger and more diverse patient populations with common comorbidities, complex medical history, concomitant medications and longer follow-up periods. To evaluate long-term clinical outcomes of the anti-TNF-α monoclonal antibody, adalimumab, in patients with psoriasis (PsO) or psoriatic arthritis (PsA) referring to an Italian dermatological centre. Single-centre retrospective real-world investigation with an observation period of up to 9 years. We reviewed the records of 316 patients (117 with PsO and 199 with PsA) treated with adalimumab and followed for up to 9 years. Safety and efficacy of adalimumab were consistent with those described in randomised controlled trials (RCTs) and other observational studies. A rapid and sustained improvement of skin lesions (evaluated as Psoriasis Area and Severity Index (PASI) 75, PASI 90 and PASI 100 response rates) was observed in the majority of patients, including those with body mass index (BMI) >30 and with prior experience of biologic therapies (including other anti-TNFs). The safety profile of adalimumab was confirmed also in elderly patients (>65 years). Our real-life experience shows that the long-term treatment with adalimumab is effective and well tolerated in psoriatic patients, including overweight/obese, elderly and anti-TNF-experienced subjects.

Methotrexate vs. Adalimumab for Psoriasis: Which Is More Effective?

Treatment options for moderate to severe psoriasis usually require systemic medications. Although a number of reports evaluate the safety, efficacy,

Myocardial infarction associated with a transiently positive lupus-anticoagulant antibody in patient taking adalimumab for psoriasis

Myocardial infarction associated with a transiently positive lupus-anticoagulant antibody in patient taking adalimumab for psoriasis

Extent and Consequences of Antibody Formation Against Adalimumab in Patients With Psoriasis

In a previously reported cohort of 29 patients with plaque-type psoriasis followed up for 24 weeks, clinically relevant antidrug antibody (ADA) to adalimumab was frequently found. Long-term data were lacking. We now present the extension of this study: 80 patients followed up for 1 year. To assess the extent of ADA and its clinical consequences after 24 weeks of adalimumab treatment for psoriasis in a cohort of 80 patients. A multicenter cohort study, performed in the outpatient dermatology clinic of 2 academic hospitals, included 80 sequential patients receiving adalimumab therapy for plaque-type psoriasis and had a follow-up of 1 year. Outcome assessors were not aware of the presence of antibodies to adalimumab or the adalimumab serum concentration when assessing patients' Psoriasis Area and Severity Index (PASI), and personnel analyzing serum samples were blinded to patients' PASI. For 80 patients treated with adalimumab for psoriasis, disease severity (PASI) was assessed, blood samples were collected, and adalimumab and ADA concentrations was determined at baseline and at weeks 12, 24, and 52. Patient PASI and adalimumab and ADA concentrations. Antidrug antibody formed in 49% of patients, before week 24 in 90% of them. Adalimumab and ADA concentrations, clinical response and ADA concentration, and adalimumab concentration and clinical response had correlations of -0.872, -0.606, and 0.519, respectively. The adalimumab dose interval was shortened because of lack of efficacy in 15 patients, 7 with and 8 without ADA; improvement in responder status occurred in 1 of 7 and 4 of 8, respectively. Patients with no ADA formation in the first 24 weeks of treatment have little chance of it in the following 24 weeks. The presence of ADA is strongly correlated with adalimumab concentration and greatly influences clinical response. If ADA is present, dose interval shortening is less useful.

Indirect comparison favors adalimumab for psoriasis

Indirect comparison favors adalimumab for psoriasis