OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.

The development of a biosimilar is based on comparative structural, physicochemical, functional and clinical assessments. The sum of these analyses encompasses the \'totality of evidence\', which demonstrates no clinically meaningful differences between the biosimilar and the reference product (RP). Once biosimilarity has been established, provided there is suitable scientific justification, clinical data may be extrapolated to other indications of the RP. AVT02 has been developed as a biosimilar to high-concentration, low-volume Humira (adalimumab), an anti-tumour necrosis factor-alpha monoclonal antibody approved for various chronic inflammatory indications. The totality of evidence for AVT02 is described, supporting its approval as an adalimumab biosimilar for all approved indications globally. Analytical similarity assessments using mass spectrometry methods demonstrated identical amino acid sequences for AVT02 and the RP, with high similarity in terms of primary structure, post-translational modifications and higher-order structural attributes. The mechanism of action was assessed by various cell-based potency assays and binding assays, and the results demonstrated that AVT02 is highly similar to the RP. No clinically meaningful differences in terms of purity, potency and safety were observed, and minor differences in a few physiochemical attributes did not impact the in vitro biologic activity and were not considered clinically relevant. Clinical similarity was demonstrated by comparing the pharmacokinetic, efficacy, safety and immunogenicity profiles of AVT02 with those of the RP. Clinical studies supported similar pharmacokinetic and comparable immunogenicity profiles between AVT02 and the RP in healthy participants and participants with moderate-to-severe chronic plaque psoriasis, with no new safety signals detected. The totality of evidence described demonstrates the biosimilarity of AVT02 to the RP, thereby fulfilling the scientific and regulatory requirements for AVT02 as a high-concentration biosimilar for the treatment of chronic plaque psoriasis and all approved indications of the RP.
Demonstrating the high similarity between the biosimilar AVT02 (adalimumab) and Humira, supporting AVT02 to be used to treat all conditions currently treated with Humira Biosimilars are drugs that have similar quality, effectiveness, and safety profiles to an already approved biological drug, which is referred to as the ‘reference product (RP)’. Although biosimilars have identical amino acids (the building blocks that make up proteins) to the RPs, they are manufactured in living cells which leads to a small amount of natural variability. Therefore, extensive testing is required to confirm that a biosimilar is highly similar to the RP. The ‘totality of evidence’ is a set of tests to demonstrate that there are no meaningful differences between the biosimilar and the RP, in other words, that there is ‘biosimilarity’ between the biosimilar and RP. Once biosimilarity has been proven, the biosimilar may be used to treat all the diseases currently treated with the RP, without the need for separate clinical trials in each disease. AVT02 has been developed as a biosimilar to Humira, an antibody approved for various chronic inflammatory diseases such as chronic plaque psoriasis (PsO). A step-by-step approach was used to show biosimilarity of AVT02 to Humira. This included clinical studies (in healthy individuals and participants with moderate to severe chronic PsO) and non-clinical studies (comparisons of the chemistry of the drugs and how they work in the body). Clinical studies in healthy individuals and participants with PsO showed that AVT02 and Humira were taken up and degraded by the body in a similar way, peoples’ immune response to the two drugs were similar, and both drugs had similar side effects. No clinically meaningful differences in the purity, effectiveness, and safety of AVT02 compared with Humira were seen. The evidence demonstrates the biosimilarity of AVT02 to Humira and supports the use of AVT02 to treat all conditions which are currently treated with Humira.

Psoriasis is a chronic and recurring condition characterized by scaly red plaques. The most common variant, plaque-type psoriasis, presents distinct clinical features. It profoundly impacts psychological and mental well-being, resulting in depression, anxiety, and suicidal thoughts. Psoriasis occurs due to disruptions in the skin\'s innate and adaptive immune response triggered by trauma, infection, or medications. Treatment options include topical therapies such as corticosteroids and vitamin D analogs, phototherapy, conventional systemic agents such as methotrexate (MTX), and biologics that target pro-inflammatory cytokines. There has been growing interest in platelet-rich plasma (PRP) as a potential treatment option for plaque psoriasis, given its lower toxicity compared to existing approaches. However, its use is not yet widespread in clinical practice due to the limited awareness of its effectiveness. This review aims to investigate the efficacy of PRP therapy for plaque psoriasis. To conduct a comprehensive analysis, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, thoroughly searching PubMed, Elton Bryson Stephens Company (EBSCO), and ClinicalTrials.gov between February and July 2023. Our focus was on patients diagnosed with plaque psoriasis, and we found multiple studies that demonstrated promising results of PRP either as monotherapy or in combination with current treatments such as MTX. The clinical evidence strongly supports the effectiveness of PRP in treating plaque psoriasis. PRP significantly improves dermatological symptoms and enhances patient and physician satisfaction. Research suggests that PRP reduces the expression of interleukin (IL) 17, a pro-inflammatory mediator, explaining its mechanism of action in treating plaque psoriasis. However, additional clinical trials with larger sample sizes, including PRP as a separate treatment group and comparisons with positive and control groups, are necessary to reinforce its efficacy in plaque psoriasis patients and elucidate other potential mechanisms underlying its beneficial effects.

This Summary of Research overviews the results of the VOLTAIRE-X study (NCT03210259), which looked at what happened when people with plaque psoriasis continually took the adalimumab reference product (adalimumab RP; known by the brand name Humira®) or switched three times between taking the adalimumab RP and BI 695501 (adalimumab-adbm, known by the brand name Cyltezo®), an adalimumab biosimilar. The VOLTAIRE-X study showed that the pharmacokinetics of adalimumab were similar in people who stayed continuously on adalimumab RP and people who switched between adalimumab RP and adalimumab-adbm. There were no differences in effectiveness, side effects, or antibodies to adalimumab when comparing people who stayed continuously on adalimumab RP with those who switched between adalimumab RP and the adalimumab biosimilar adalimumab-adbm. On the basis of these results, adalimumab-adbm was approved by the US Food and Drug Administration (FDA) as interchangeable with adalimumab RP, meaning that a pharmacist can substitute the biosimilar adalimumab-adbm for adalimumab RP without requiring permission from the original prescriber (unless required to by state law).

UNASSIGNED: Psoriasis is a chronic, immune mediated inflammatory condition of the skin and imbalance in inflammatory mediators could result in insulin resistance, metabolic syndrome and facilitate the occurrence and progression of Non-alcoholic fatty liver disease (NAFLD).
UNASSIGNED: Primary objectives: To study the frequency of NAFLD in cases of chronic plaque psoriasis and controlsTo study the interleukin levels in cases of chronic plaque psoriasis and controls. Secondary objectives: To study the BMI, lipid profile, waist circumference, FBS (fasting blood sugar), PPBS (post prandial blood sugar) and serum insulin in cases and controlsTo study the association of age, duration of psoriasis, PASI (psoriasis area severity index), BSA (body surface area) involved, BMI (body mass index), lipid profile, obesity, waist circumference, FBS (fasting blood sugar), PPBS (post prandial blood sugar) and serum insulin levels with NAFLD in patients of chronic plaque psoriasisTo correlate serum levels of IL1-β, IL6 and TNF-α with NAFLD in patients of chronic plaque psoriasis.
UNASSIGNED: 50 clinically diagnosed cases of chronic plaque psoriasis with age ≥ 18years, diseases duration ≥ 6 months and 30 age and sex matched controls were recruited. PASI, BSA of cases was calculated and BMI, BP, WC of all subjects was measured. Serum lipid profile, FBS, PPBS, insulin level, IL1- β , IL6, TNF- α , high frequency B-mode ultrasound, LFT and fibroscan were done in all subjects.
UNASSIGNED: 28(56.0%) cases and 2(6.6%) controls had NAFLD with statistically significant difference. Significantly elevated WC, serum insulin, deranged lipid profile, fatty liver, transaminitis, fibroscan score, liver fibrosis, NAFLD and interleukins were found in cases vs controls. There was a significant association of NAFLD in psoriatic patients with increasing duration of psoriasis, BMI ≥23 Kg/m2, high WC, increasing BSA involved, deranged lipid profile, raised total cholesterol levels and increasing number of risk factors. Nonsignificant but positive association of NAFLD in cases was found with high levels of IL1 - β, IL - 6, TNF-α, FBS and increasing PASI.
UNASSIGNED: Significantly increased interleukin levels and their weak positive correlation with the severity of psoriasis (PASI, BSA) in patients of chronic plaque psoriasis explains the possible role of inflammation in the causation of psoriasis. Screening may be considered in psoriatic patients with increasing duration of psoriasis, high WC, high BSA involved, high BMI, obesity, dyslipidemia and insulin resistance.
UNASSIGNED: Small sample size.
UNASSIGNED: NONE.

UNASSIGNED: Psoriasis is a chronic inflammatory skin disease affecting approximately 60 million people worldwide. Genome-wide association studies (GWAS) have allowed identification of novel therapeutic targets in psoriasis including tyrosine kinase 2 (TYK2) where an exonic variant within the gene increases the risk of developing psoriasis.
UNASSIGNED: This review discusses the role of TYK2 in psoriasis pathogenesis, how that relates to genetic variants and recently published ground-breaking clinical trials of novel TYK2 inhibitors. Keyword searches of PubMed were made until January 2023, using the terms: \'TYK2 inhibitor,\' \'TYK2 inhibitor AND psoriasis\' and \'TYK2 AND GWAS.\' Articles and references have been thoroughly reviewed by the authors.
UNASSIGNED: The TYK2 inhibitor deucravacitinib shows promise as an effective oral agent for treating psoriasis. Longer term data are needed to know if thrombotic risk/cancer risk is distinct from other Janus kinase (JAK) inhibitors. Psoriasis is a complex genetic disease for which risk is influenced by genes and environmental factors. GWAS studies have identified several regions of DNA associated with increased risk of disease. We believe that pathway analysis by genetic and genomic means will be key to optimizing TYK2 therapy for the right person at the right time.

UNASSIGNED: A sustained inflammatory state of psoriasis causes comorbidities such as psoriatic arthritis, metabolic syndrome (MetS), and cardiovascular disease.
UNASSIGNED: To note the duration and severity of psoriasis, assess prevalence of MetS, and correlate these with indicators of sub-clinical atherosclerosis.
UNASSIGNED: Thirty-two patients of chronic plaque psoriasis were enrolled in the study. Their demographic particulars, clinical details, results of investigations to assess MetS, and indicators of sub-clinical atherosclerosis, namely, carotid intimal media thickness (CIMT) measured using B-mode USG and epicardial fat thickness (EFT) using 2-D ECHO, were recorded.
UNASSIGNED: The study participants were predominantly male (2.5:1); their mean age was 40.45 ± 12.42 years, the median disease duration (DD) was 2 years, and the mean psoriatic area severity index (PASI) score was 8.62 ± 7.49. Mild disease (PASI <5) was present in 12 participants (37.5%), and shorter DD (<5 years) was present in 16 (50%) participants. MetS, detected in 11 (37.5%) study participants, was not significantly associated with CIMT, EFT, DD, and PASI. CIMT and EFT too did not correlate significantly with DD, PASI, or measures of MetS. Neither did there exist any significant correlation between CIMT and EFT.
UNASSIGNED: Sub-clinical atherosclerosis in our study participants was not significantly associated with either measures of MetS or duration/severity of psoriasis.

BACKGROUND: Methotrexate is an antimetabolite anticancer drug frequently used in the treatment of extensive chronic plaque psoriasis. Psoriasis patients on treatment with immunosuppressants have an increased risk of developing malignancies.
OBJECTIVE: To present a rare case of Oral Squamous Cell Carcinoma (OSCC) in a psoriasis patient postacute methotrexate toxicity.
METHODS: A 47-year-old female, a known case of chronic plaque psoriasis for which she was on 15 mg/ week methotrexate therapy and accidentally consumed 15 mg for 7 consecutive days. She was successfully treated for methotrexate toxicity and 45 days later she presented with exophytic growth on the tongue. Histopathology confirmed the diagnosis of squamous cell carcinoma and the patient underwent surgical resection.
CONCLUSIONS: There could be a causal association between psoriasis and OSCC in the setting of acute methotrexate toxicity, as in the present case.

Psoriasis is a chronic multisystem inflammatory disease associated with a plethora of comorbidities including metabolic syndrome, cardiovascular disease, hypertension, diabetes, hyperlipidemia, obesity, anxiety, depression, chronic kidney disease, and malignancy. Advancement in unveiling new key elements in the pathophysiology of psoriasis led to significant progress in the development of biologic agents which target different signaling pathways and cytokines involved in the inflammatory cascade responsible for the clinical manifestations found in psoriasis. Currently available novel therapeutic options for moderate-severe psoriasis include tumor necrosis factor alpha inhibitors, inhibitors of the interleukin 17, and inhibitors of the interleukin 23. Nevertheless, concerns have been raised with respect to the possible risks associated with the use of biologic therapy requiring close collaboration between dermatologists and physicians of different specialties. Our aim was to perform an in-depth literature review and discuss the potential risks associated with biologic therapy in patients with psoriasis and concurrent diseases with a focus on the influence of novel therapeutic agents on liver function in the context of hepatopathies, particularly viral hepatitis. A multidisciplinary teamwork and periodic evaluation of psoriasis patients under biologic therapy is highly encouraged to obtain an accurate management for each case.

This comparative observational study aimed to validate an online Patient-oriented Psoriasis Area and Severity Index (PO-PASI) by comparing it against the Psoriasis Area and Severity Index (PASI), of 97 adult participants with chronic plaque psoriasis. Pearson\'s correlation coefficient of 0.866 (P-value = 0.0001) showed a strong positive linear correlation, and interclass correlation coefficients [ICC scores = 0.864 [95% confidence intervals (CIs) (0.803 < ICC < 0.907)]] suggest an interrater reliability of \'good\' to \'excellent\' when comparing PO-PASI to the PASI score. Additionally, we compared PO-PASI and PASI with DLQI and demonstrated an overall stronger positive correlation between PO-PASI and DLQI when compared to PASI.