A single-centre, observational, retrospective, real-life study evaluating adalimumab biosimilar ABP 501 in the treatment of plaque-type psoriasis and psoriatic arthritis in originator-naïve patients and in patients undergoing non-medical switch from originator.

BACKGROUND: ABP 501 is a biosimilar to the anti-tumor necrosis factor-alfa monoclonal antibody adalimumab and despite its effectiveness and safety in the treatment of psoriasis was demonstrated in randomized clinical trials, no real-life data are available, in particular in patients undergoing non-medical switch from originator to biosimilar. METHODS: We retrospectively searched our clinical records for all patients receiving ABP 501 between March 10, 2019 and September 7, 2019 at our Department. Therefore, we identified 94 patients, 46 patients underwent non-medical switch from adalimumab reference product to ABP 501. RESULTS: In originator-naïve patients, mean PASI significantly improved from baseline to week 24 (p < .0001) in both Pso and PsA cohorts. In these patients, mean DAS-28 ESR improved with no significant differences from baseline. In patients undergoing non-medical switch from adalimumab reference product to ABP 501, no significant difference in PASI or DAS-28 ESR were observed from week 16 before switch to week 24 after switch. CONCLUSIONS: AB- 501 is an effective treatment for plaque-type psoriasis and psoriatic arthritis regardless if patients are originator-naïve or if they were switched from the reference product.

Adalimumab in children and adolescents with severe plaque psoriasis: a safety evaluation.

Introduction: Psoriasis is a chronic inflammatory systemic disease that affects 2% of the population and is associated with an important physical and physiological burden. About 0.5-2% of psoriatic cases onset during the pediatric age range, and often it's not diagnosed until adulthood. Adalimumab is an antitumor necrosis factor monoclonal antibody approved for use in children in 2008 and now it was used in several diseases in rheumatology, gastroenterology, and in dermatology.Areas covered: The purpose of this article was to summarize what has been described in the literature so far, about safety in the use of adalimumab in pediatric psoriasis. The presented data was extrapolated from a literature review from PubMed searches (using words 'pediatric psoriasis,' 'adalimumab children,' 'adalimumab safety,' 'pediatric psoriasis treatment,' 'adalimumab clinical trial'), treatment guidelines, and reports from European and United States regulatory agencies.Expert opinion: Actually there are some biologic agents for the treatment of pediatric psoriasis, but the lack of safety data from controlled trials is evident. The safety data on the use of adalimumab in pediatric psoriasis was taken from long-term studies in the adult population. These studies confirm the data on the safety of the drug as it is also supported by several works on real-life.

HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct-acting antivirals.

Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV) hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate HBV when HCV is suppressed or cleared by direct-acting antivirals (DAAs). We assessed the prevalence of overt or previous HBV coinfection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV-RNA and HBV-DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow-up. At the start of DAAs, eight patients (7.7%) were HBsAg positive/HBeAg negative with undetectable HBV-DNA and low levels of quantitative HBsAg (four on nucleos(t)ide analogues [NUCs] and four inactive carriers), 37 patients (35.6%) had markers of previous HBV infection (25 anti-HBc positive, 12 anti-HBc/anti-HBs positive) and 59 (56.7%) had no evidence of HBV infection. Sixty-seven patients (64.4%) were HCV-RNA negative at week 4 and 98 (94.2%) achieved sustained virological response. All four HBsAg-positive patients treated with NUCs remained HBV-DNA negative, but three of four untreated patients showed an increase in HBV-DNA of 2-3 log without a biochemical flare and achieved HBV-DNA suppression when given NUCs. During or after DAAs, by conventional assay, HBV-DNA remained not detectable in all 37 anti-HBc-positive patients but in three of them (8.1%) HBV-DNA became detectable with a highly sensitive PCR. HBV reactivation is likely to occur in untreated HBV/HCV-coinfected cirrhotic patients when they undergo HCV treatment with DAAs. Pre-emptive therapy with NUCs should be considered in this setting. Anti-HBc-positive patients rarely reactivate HBV without clinical or virological outcomes.

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

BACKGROUND: 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. OBJECTIVES: 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. METHODS: Single-centre retrospective real-world investigation with an observation period of up to 9 years. RESULTS: 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). CONCLUSION: 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.

Quantification of fibrosis by collagen proportionate area predicts hepatic decompensation in hepatitis C cirrhosis.

BACKGROUND: It is unclear whether the course of cirrhosis and its prognosis are related to the amount of collagen in the liver. AIM: To determine whether fibrosis, assessed by collagen proportionate area (CPA) in patients with compensated cirrhosis, is associated with the presence of oesophageal varices, and predict disease decompensation during the follow-up period. METHODS: We prospectively evaluated 118 consecutive patients with compensated cirrhosis to correlate fibrosis, assessed by CPA in liver biopsies, with the presence of oesophageal varices (OV) and with the rate of liver decompensation (LD) development during a median follow-up of 72 months. RESULTS: At baseline 38 (32.2%) patients had OV and during the follow-up (median 72 months, IQR 47-91), 17 patients (14.4%) developed LD. The mean CPA value was different in patients with and without OV (14.8 ± 5.9% vs. 21.6 ± 9.5%, P < 0.001). The best CPA cut-off for OV by area under the receiver operating characteristic (AUROC) was ≥14% and with multivariate logistic analysis CPA was the only variable associated with OV (OR: 28.32, 95% CI: 6.30-127.28; P < 0.001). By AUROC analysis the best CPA cut-off to predict LD was 18.0%. By Cox regression multivariate analysis CPA ≥18% (HR: 3.99, 95% CI: 1.04-11.45; P = 0.036), albumin (HR: 0.12, 95% CI: 0.04-0.43; P = 0.001) and presence of OV (HR: 8.15, 95% CI: 2.31-28.78; P = 0.001) were independently associated with LD. CONCLUSION: Quantification of fibrosis by collagen proportionate area allows identification of patients with compensated HCV cirrhosis with a higher likelihood of clinically relevant portal hypertension and a higher risk of decompensation.

Pharmacogenetics of psoriasis: HLA-Cw6 but not LCE3B/3C deletion nor TNFAIP3 polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab.

BACKGROUND: Our understanding of the genetic basis of predisposition to psoriasis is increasing exponentially due to the progress of genetic studies. However, so far little is known about genetic predisposition in relation to the response to psoriasis treatments. Recent data identified genetic predictors for the clinical outcome of conventional treatments such as methotrexate, acitretin and vitamin D derivatives, but few studies are available on genetic predictors of response to biologics. We hypothesized that genetic variations associated with increased risk of developing psoriasis may also act as predictors for the outcome of biologic therapy. OBJECTIVES: The aim of our study was to analyse the presence of three different psoriasis susceptibility genetic variations (HLA-Cw6; TNFAIP3 rs610604 polymorphism; LCE3B/3C gene deletions) in a cohort of patients affected by moderate to severe psoriasis under ustekinumab treatment. Our primary endpoint was to evaluate the association between Psoriasis Area and Severity Index (PASI) 75 response at week 12 and HLA-Cw6 status. METHODS: Fifty-one patients were genotyped by standard methods and psoriasis severity (PASI score) was evaluated at day 0 and after 4, 12, 24 and 40 weeks of treatment. RESULTS: We observed increased response to ustekinumab in Cw6-positive (Cw6POS) patients [PASI 75 at week 12: 96·4% in Cw6POS vs. 65·2% in Cw6-negative (Cw6NEG) patients; P = 0·008]. In addition, we show that HLA-Cw6POS patients responded faster to ustekinumab, 89·3% of them reaching PASI 50 at week 4, after a single injection (vs. 60·9% of HLA-Cw6NEG patients). The superior response of HLA-Cw6POS patients was maintained throughout the study period, reaching the highest statistical significance for PASI 75 at week 28 (96·35% Cw6POS vs. 72·7% Cw6NEG; odds ratio 9·8). Analysis of TNFAIP3 rs610604 polymorphism and LCE3B/3C gene deletions did not show any significant association with response to ustekinumab. CONCLUSIONS: Our observations underline the role of HLA-Cw6 not only as a psoriasis susceptibility gene, but also as a pharmacogenetic marker of response to ustekinumab in psoriasis.

Evaluation of clinical and ultrasonographic parameters in psoriatic arthritis patients treated with adalimumab: a retrospective study.

OBJECTIVES: The aim of this study was to evaluate clinical and US-PD parameters in PsA during adalimumab treatment. METHODS: A retrospective study has been conducted in forty patients affected by moderate-to-severe peripheral PsA. Clinical, laboratory, and US-PD evaluations were performed at baseline, after 4, 12, and 24 weeks of treatment. They included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analogue scale (VAS), Health Assessment Questionnaire (HAQ) modified for Spondyloarthritis, Psoriasis Area Severity Index (PASI) score, the 28-joint Disease Activity Score (DAS 28), and US-PD assessment. US-PD findings were scored according to a semiquantitative scale (ranging 0-3) for synovial proliferation (SP), joint effusion (SE), bone erosions (BE), and PD. RESULTS: Data obtained for clinical, laboratory findings and US-PD evaluation showed statistical significant improvement in all the measures performed except for BE. A significant parallel decrease in SE, SP, and PD values were demonstrated. CONCLUSION: This study demonstrated that US-PD is a valid technique in monitoring the response to adalimumab in moderate-to-severe PsA.