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Introduction and aim. Inflammatory bowel diseases (IBD) include Crohn's disease. The etiology has not been fully elucidated, however, one pathomechanism is an abnormal immune response. It is likely led by a complex relationship between genetic susceptibility, environmental factors and the gut microbiota. Clinical manifestations during disease exacerbations include abdominal pain, chronic diarrhea and weight loss, which can negatively affect patients' quality of life. Treatment of the disease is multidirectional, and one of the therapeutic options is biological therapy, which includes drugs, such as infliximab, adalimumab, natalizumab, certolizumab, etc. The mechanism of action of adalimumab is to block the connection between tumor necrosis factor alpha and its receptor on the cell, which reduces inflammation, while ustekinumab inhibits interleukin-12 and -23, leading to a reduction in the production of cytokines and inflammatory factors. Description of the case. The patient began his medical history in 2009, when he was admitted to the hospital with persistent abdominal pain, fever and weight loss. During his hospitalization, he underwent repeated laboratory and imaging tests. He was subjected to such therapy, which included the administration of monoclonal antibodies: infliximab, vedolizumab, adalimumab, ustekinumab. After each of the above-mentioned drugs, no satisfactory immune response was achieved. The longest remission, which lasted about 2 years, was achieved after administration of adalimumab. Conclusion. After the patient's clinical condition deteriorated, it was decided, with the approval of the bioethics committee, to start treatment with two biologic drugs. Improvement in the patient's condition was observed after three months when adalimumab and ustekinumab were administered simultaneously. Both of these drugs are described in the scientific literature and used in the treatment of moderate to severe forms of CD. [ABSTRACT FROM AUTHOR]

The neuroinflammatory response triggered by cerebral ischemia-reperfusion injury (CIRI) is characterized by the upsurge of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, which promote leukocyte infiltration and subsequent accumulation in the ischemic zone. This accumulation further intensifies inflammation and aggravates ischemic damage. Certolizumab pegol (CZP), a monoclonal antibody targeting TNF-α, is widely used in treating various inflammatory diseases. This study explored the therapeutic potential of CZP in a mouse model of CIRI, induced by middle cerebral artery occlusion (MCAO), focusing on its influence on the microglial inflammatory response. In vitro analyses revealed that CZP markedly inhibits TNF-α-stimulated inflammation in primary microglia with an EC 50 of 1.743 ng/mL. In vivo, MCAO mice treated with CZP (10 μg/mouse, i.p.) for 3 days showed reduced infarct volume, partially improved neurological function, and diminished blood-brain barrierdisruption. Additionally, CZP treatment curtailed microglial activation and the release of pro-inflammatory mediators in the early stages of stroke. It also favorably modulated microglial M1/M2 polarization, rebalanced Th17/Treg cells dynamics, and inhibited Caspase-8-mediated GSDMD cleavage, preventing microglial pyroptosis. Collectively, this study described that the treatment with CZP reversed damaging process caused by CIRI, offering a promising therapeutic strategy for the treatment of ischemic stroke., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Psoriasis is a chronic, inflammatory skin disease that may occur at any age, with a bimodal peak of incidence around the age of 16–20 years of age (early onset) and 57–60 years (late-onset). It is estimated that roughly 70% of patients develop the disease before the age of 40, which coincides with the reproductive years. Moreover, psoriasis is a chronic disease, meaning that, with increased life-duration expectancy, the number of patients affected with psoriasis aged over 65 years is going to increase and represent a big therapeutic challenge. Actually, no specific drug recommendation is available, based only on the age of the patients, while therapeutic prescription should take into account that elderly patients have more comorbidities than younger patients, with polypharmacy and an increased risk of drug interactions. Women with psoriasis are more likely to report a worse influence of the disease on their quality of life, and they are more susceptible to the development of depression. Furthermore, pregnancy and lactation represent a major contraindication to several systemic agents, and only a few studies exist providing the safety of certain drugs during these periods of life of a woman, such as certolizumab pegol. In this paper, we discuss systemic therapeutic strategies, including conventional and biological therapies, in a special subset of patients affected with moderate-to-severe psoriasis focusing on elderly patients and on female patients in fertile age, pregnancy, and lactation. [ABSTRACT FROM AUTHOR]

Background: Biopharmaceuticals revolutionised inflammatory bowel disease (IBD) treatment. However, it is postulated they compromise immunity, collagen production and angiogenesis resulting in infective post-operative complications and altered wound/anastomotic healing. Research has failed to agree on risks associated with perioperative biologics therefore it was anticipated that a systematic review may provide a consensus and contribute recommendations for clinical practice.Methods: A systematic review conducted as per PRISMA guidelines included a methodical search of PubMed, Google Scholar, EMBASE/Ovid and Cochrane Library using MeSH and/or keywords for papers published between 01/01/1998 and 04/02/2019.The population analysed included adult ulcerative colitis, Crohn's disease, Indeterminate Colitis or IBD unclassified patients. The intervention was intra-abdominal surgery in patients treated with biological therapy in the preceding 12 weeks compared to patients who had intra-abdominal surgery without biological therapy within the defined timeframe. The primary outcome was surgical site infection (SSI) with secondary outcomes including wound dehiscence, intra-abdominal sepsis/abscess, systemic infection and anastomotic breakdown within 30 days post-procedure. Papers were evaluated by two independent reviewers and those included were assessed for quality/bias using the Newcastle-Ottowa scale.Results: 2064 UC, Crohn's and IC patients were analysed across 8 included studies. Several studies' multivariate analyses demonstrated corticosteroids to be independent predictors of morbidity. There are no increased complications associated with anti-TNFα exposure while vedolizumab increased SSI and small bowel obstruction.Conclusion: Prospective studies and randomised control trials are required to clarify study outcomes and recommendations published to date. Presently, biologics should continue to be used and considered beneficial in this population. [ABSTRACT FROM AUTHOR]

Aims: The use of swollen (SJC) and tender joint counts (TJC) for rheumatoid arthritis (RA) disease activity and treatment effectiveness is well established. Patient-reported outcomes (PRO) are important. However, it is unknown if patient scoring is as reliable as that of trained professionals., Methods: PRO including SJC and TJC were assessed at baseline, 6 and 12 weeks by patients and clinicians. Data were collected using ePRO (electronic) and pPRO (paper). The Least Squares Method (LSM), Pearson correlation (Rs) and weighted Kappa scores were used to assess inter-rater reliability and agreement of responses between the patient, nurse and physician for changes in TJC and SJC from 0 to 12 weeks of treatment., Results: There was a total of 341 evaluable matched joint assessment in 52 patients with RA: 157 nurse, 106 patient and 78 physician. There were matched joint count pairs for 104 patient-nurse, 72 physician-nurse and 21 patient-physician. Correlation (R) of TJC scores were as follows: patient-nurse 0.83 (P < 0.001), physician-nurse 0.85 (P < 0.001) and physician-patient 0.59 (P = 0.005). The inter-rater reliability (agreement) of the patient-nurse pairs had a weighted Kappa of 0.59 (0.53, 0.68). Correlation (R) of SJC scores were as follows: patient-nurse 0.69 (P < 0.001), physician-nurse 0.66 (P < 0.001) and physician-patient 0.42 (P = 0.058). The inter-rater reliability (agreement) of the patient-nurse pairs had a weighted Kappa of 0.48 (0.41, 0.55)., Conclusions: There is a moderate to high level of agreement between clinicians and patient TJC and SJC assessments that suggest it may be a useful option in assessing joints and response in RA. Further evaluation of RA activity tools such as Disease Activity Score of 28 joints, Crohn Disease Activity Index or Simple Disease Activity Index utilizing patient assessments may be worth exploring., (© 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Introduction: Certolizumab pegol (CZP) is an anti-tumor necrosis factor alpha (TNFα) approved for the treatment of moderate to severe plaque psoriasis (PSO). However, data on its real-world use is currently limited. The objective of this study was to describe the 1-year real-world effectiveness of CZP, its impact on health-related quality of life (HRQoL), and safety outcomes in patients with moderate to severe PSO in multi-country settings. Methods: CIMREAL, a prospective, noninterventional study, was conducted across Europe and Canada from August 2019 to December 2022. Patients were followed for 1-year, receiving CZP 400 mg initial doses at weeks 0, 2, and 4, followed by CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg Q2W maintenance dosing. Effectiveness was assessed using the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI). Safety was also evaluated. Results: Overall, 399 patients with moderate to severe PSO were included. Of these, 93.7% (374/399) and 77.9% (311/399) completed months 3 and 12, respectively. Mean age (± standard deviation) was 42.9 ± 13.5 years and body mass index was 28.5 ± 6.8 kg/m2, with the majority of patients being female (68.2%). At 12 months, CZP showed substantial effectiveness, achieving PASI 75 and PASI 90 response rates (≥ 75% and ≥ 90% improvement from baseline, respectively) of 77% and 56.5%, respectively. Patients with PASI score of ≤ 3 and ≤ 2 experienced improvement from 3 months (49.8% and 41.1%, respectively) to 12 months (82.0% and 75.3%, respectively). HRQoL considerably improved, with mean DLQI scores decreasing from 12.4 to 2.3 after 12 months of treatment, and the proportion of patients with DLQI 0/1 increased from 28.6% at 3 months to 59.4% at 12 months. The 1-year probability of persistence was approximately 85%. Overall, 30.6% of the patients experienced any adverse events and 9.3% had serious adverse events. Conclusion: In routine clinical practice, CZP exhibited consistent effectiveness, positively impacting both skin psoriasis activity and HRQoL. The 1-year persistence of CZP was high, and no new safety signals were identified. Trial Registration Number: ClinicalTrials.gov Identifier: NCT04053881 https://www.clinicaltrials.gov/study/NCT04053881. [ABSTRACT FROM AUTHOR]

The appearance of biologic agents for the treatment of diverse autoimmune diseases in particular rheumatoid arthritis at the end of the 1990s changed the treatment of these patients. With the introduction of new agents in the treatment of rheumatic diseases, we started to notice the presence of new and sometimes unexpected adverse events. It is well recognized that infections are the main concern with these types of treatments; however, the occurrence of autoimmune abnormalities is also seen and its gaining perhaps more attention as the use of these agents is increasing. The first clinical trials of anti-tumor necrosis factor-α (anti-TNFα) inhibitors showed an increase of antinuclear and anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies in patients treated with these agents. In this paper, we review the frequency of these autoantibodies in patients treated with biologic agents, particularly anti-TNF-α inhibitors, and its correlation with autoimmune processes as well as the clinical relevance of such findings. [ABSTRACT FROM AUTHOR]

Background: Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are highly effective in treating rheumatoid arthritis (RA), albeit high drug cost has restricted their use in many countries. As a countermeasure, Norway implemented pharmaceutical tendering as a cost-reducing strategy. The aim of this study was to assess the annual proportion of different b/tsDMARDs registered to treat RA patients under the influence of a Norwegian pharmaceutical tendering between 2010 and 2019. Method: The data is collected from ten Norwegian outpatient centers. The included patients are categorized as naïve, non-naïve, and current b/tsDMARD users. 13 individual b/tsDMARDs are assessed and compared with the tender rankings from each year. Overview of subcutaneous (sc) with per oral vs. intravenous (iv) and biosimilars vs. non-biosimilar are also described. Result: The tender-winning b/tsDMARD was the most or second most used drug in nine out of ten years for naïve users, seven for non-naïve users, and twice for current users. The average sum of the highest and second highest proportion among naïve, non-naïve, and current b/tsDMARD users were 75%, 53%, and 50% during the ten years, respectively. The tender-winning drug was iv in eight out of ten years. However, the average total proportion of sc and per oral b/tsDMARDs was about 70% for naïve b/tsDMARD users, 50% for non-naïve b/tsDMARD users, and 60% for current b/tsDMARD users. The main contributors to sc and per oral b/tsDMARD were etanercept (reference and biosimilar) and certolizumab pegol. The main contributors to iv b/tsDMARD were rituximab reference and infliximab biosimilar. Despite low-ranking offers, rituximab reference (offered as a second-line drug) often achieved a high proportion among non-naïve and current b/tsDMARD users. After the introduction of biosimilars, their average proportion was about 40%, 40%, and 20% for naïve, non-naïve, and current b/tsDMARD users, respectively. Conclusion: Based on observed data, a higher tender rank was associated with a higher proportion among naïve and non-naïve b/tsDMARD users. However, in most cases, sc b/tsDMARDs achieved a higher proportion with lower tender ranks than iv b/tsDMARDs with higher tender ranks. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to retrospectively examine the drug survival of tumor necrosis factor (TNF)-alpha inhibitors and switched subsequent biologic agents after discontinuation of TNF inhibitors. Methods: This real-world setting study was conducted at a single academic center. We included patients who were treated with adalimumab (n = 111), certolizumab pegol (n = 12), and infliximab (n = 74) at Jichi Medical University Hospital from 1 January 2010 to 31 July 2021. Results: No significant differences were noted in drug survival between the three TNF inhibitors. The 10-year drug survival rate for adalimumab and infliximab was 14% and 18%, respectively. Of the patients who discontinued TNF inhibitors for any reason (n = 137), 105 chose biologics as their subsequent treatment. The subsequent biologics included 31 cases of TNF inhibitors (adalimumab in 20, certolizumab pegol in 1, and infliximab in 10), 19 of interleukin-12/23 inhibitor (ustekinumab), 42 of interleukin-17 inhibitors (secukinumab in 19, brodalumab in 9, and ixekizumab in 14) and 13 of interleukin-23 inhibitors (guselkumab in 11, risankizumab in 1, and tildrakizumab in 1). Cox proportional hazards analysis for the subsequent drugs in cases of discontinuation due to inadequate efficacy revealed that female sex was a predictor of drug discontinuation (hazard ratio 2.58, 95% confidence interval 1.17–5.70) and that taking interleukin-17 inhibitors rather than TNF inhibitors was a predictor of drug persistence (hazard ratio 0.37, 95% confidence interval 0.15–0.93). Conclusions: Interleukin-17 inhibitors may be a favorable option for patients who need to switch from TNF inhibitors due to inadequate efficacy. However, this study is limited by the small number of cases and its retrospective design. Plain Language Summary: With many biologic options available for the treatment of psoriasis, choosing the optimal drug can be challenging, especially when switching drugs. Tumor necrosis factor (TNF) inhibitors are the oldest category of biologics used for psoriasis, with adalimumab and infliximab being available since 2010 and certolizumab pegol since 2019 in Japan. In this study, we examined the drug survival of TNF inhibitors in patients treated with adalimumab (n = 111), certolizumab pegol (n = 12), and infliximab (n = 74) at Jichi Medical University Hospital from 1 January 2010 to 31 July 2021. No significant differences were noted in drug survival between the three TNF inhibitors, and the 10-year drug survival rate for adalimumab and infliximab was 14% and 18%, respectively. We examined the drug survival of subsequent biologics used by patients who discontinued TNF inhibitors for any reason (n = 137) and found that among patients who discontinued TNF inhibitors due to inadequate efficacy, female sex was a predictor of drug discontinuation and that taking interleukin-17 inhibitors rather than TNF inhibitors was a predictor of drug continuation. The study results suggest that interleukin-17 inhibitors is a favorable option for patients who discontinue TNF inhibitors due to inadequate efficacy and need to switch to other agents. However, this study has limitations, including the small number of cases and the single-center and retrospective study design. [ABSTRACT FROM AUTHOR]

Objectives Interventions aimed at increasing TNF-α inhibitor serum drug levels (SDLs) may improve treatment response; however, previous studies suggesting SDL cut-offs have not accounted for treatment adherence. The aim of this study was to establish the relationship between adalimumab/certolizumab SDLs and EULAR good vs non-/moderate response and to define SDL cut-offs associated with good response in fully adherent patients. Methods In a prospective observational study, 475 patients with RA were treated with certolizumab (n  = 192) or adalimumab (n  = 283). At baseline and 3, 6 and 12 months, patients had 28-joint DAS, self-reported treatment adherence and SDLs measured. Fully adherent patients were analysed as a subgroup. Follow-up data at 3, 6 and 12 months were analysed separately. Median SDLs were compared in good vs non-/moderate response patients and receiver operating characteristics (ROC) curves were used to establish cut-off SDLs. Results Fully adherent good responders had significantly higher median adalimumab/certolizumab SDLs compared with non-/moderate responders (P  = 0.04 and P  = 0.0005, respectively). ROC analysis reported 3 month non-trough adalimumab SDLs discriminated good vs non-/moderate response with an area under the curve (AUC) of 0.63 (95% CI 0.52, 0.75), with a cut-off of 7.5 mg/l being 39.1% specific and 80.9% sensitive. Similarly, 3 month non-trough certolizumab SDLs discriminated good vs non-/moderate response with an AUC of 0.65 (95% CI 0.51, 0.78), with a cut-off of 26.0 mg/l being 43.9% specific and 77.8% sensitive. Conclusion In fully adherent patients, higher SDLs are detected in good responders, suggesting that interventions to improve SDLs, such as encouraging adherence, could improve treatment response. The 3 month non-trough SDL cut-offs of 7.5 mg/l for adalimumab and 26.0 mg/l for certolizumab may be useful in clinical practice. [ABSTRACT FROM AUTHOR]

Anti-tumour necrosis factor (TNF)-α agents have been increasingly used to treat patients affected by inflammatory bowel disease and dermatological and rheumatologic inflammatory disorders. However, the widening use of biologics is related to a new class of adverse events called paradoxical reactions. Its pathogenesis remains unclear, but it is suggested that cytokine remodulation in predisposed individuals can lead to the inflammatory process. Here, we dissect the clinical aspects and overall outcomes of autoimmune diseases caused by anti-TNF-α therapies. [ABSTRACT FROM AUTHOR]

The author found that anti-tumor necrosis factor (anti-TNF) therapy prior to elective surgery may increase the odds of postoperative infection in Crohn's disease (CD). We also read two meta-analyses about the risk of postoperative complications following preoperative anti-TNF therapy in patients with CD [[2]]. Keywords: Crohn's disease; Anti-TNF agents; Elective surgery; Complications EN Crohn's disease Anti-TNF agents Elective surgery Complications 1421 1422 2 04/06/22 20220401 NES 220401 We read with interest the article by Hanzel et al. [[1]] conducting a systematic review and meta-analysis to investigate the relationship between preoperative biological therapy and postoperative outcomes in inflammatory bowel disease (IBD) focusing on elective surgery. [Extracted from the article]

Background: Treatment of rheumatoid arthritis (RA) includes the use of conventional (cs), biologic (b) disease-modifying anti-rheumatic drugs (DMARDs) and oral, intramuscularly, intravenous, or intraarticular (IA) glucocorticoids (GCs). In this paper, we analysed whether a treat-to-target (T2T) strategy optimizing csDMARD, oral, and IA-GC treatment as an adjunct new therapy to a new certolizumab pegol (CZP) therapy improves the effectivity in RA patients. Methods: 43 patients with active RA (≥6 tender, ≥6 swollen joints, ESR ≥ 20 mm/h or CRP ≥ 7mg/L) despite csDMARD treatment for ≥ 3 months and naïve to bDMARDs were randomized to CZP (200 mg/2 weeks after loading with 400 mg at weeks 0–2–4) plus a treat-to-target strategy (T2T, n = 21), or to CZP added to the established csDMARD therapy (fixed regimen, n = 22). The T2T strategy consisted of changing the baseline csDMARD therapy (1) SC-methotrexate (dose: 15 ≥ 20 ≥ 25 mg/week, depending on the initial dose) ≥ leflunomide (20 mg/d) ≥ sulphasalazine (2 × 1000 mg/d) plus (2) oral GCs (prednisolone 20–15–12.5–10–7.5–5–2.5–0 mg/d tapered every five days) and (3) injections of ≤5 affected joints with triamcinolone. DMARD modification and an addition of oral GCs were initiated, depending on the achievement of low disease activity (DAS 28 < 3.2). The primary objective was defined as the ACR 50 response at week 24. Results: ACR 50 was achieved in 76.2% of the T2T, as compared to 36.4% of the fixed regimen patients (p = 0.020). ACR 20 and 70 responses were achieved in 90.5% and 71.4% of the T2T patients and 59.1% and 27.3% of the fixed regimen patients, respectively (p = 0.045 and p = 0.010, respectively). The adverse event rate was similar for both groups (T2T n = 51; fixed regimen n = 55). Conclusion: Treat-to-target management with the optimization of csDMARDs, oral, and IA-GCs of RA patients in parallel to a newly established CZP treatment was safe and efficacious in comparison to a fixed regimen of csDMARDs background therapy. [ABSTRACT FROM AUTHOR]

Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed. [ABSTRACT FROM AUTHOR]

It is important to emphasize that nails respond much more slowly to therapy compared to skin and assessment of efficacy should be made after a minimum of 3-6 months of treatment, especially in severe nail matrix disease. Managing nail psoriasis adequately is of great importance, considering its strong association with psoriatic arthritis (PsA) and its impact on patients' quality of life (QoL). MTX is more effective for nail matrix involvement.Acitretin (0.2-0.4 mg/kg/day): The use of acitretin (0.2-0.4 mg/kg/d) is controversial, since it is a rather slow-acting compound, with moderate efficacy and could cause nail thinning and paronychia. 4 ACIT, acitretin; ADA, adalimumab; APR, apremilast; BROD, brodalumab; CERTO, certolizumab pegol; CYCLO, cyclosporin; ETA, etanercept; GUS, guselkumab; IFX, infliximab; IXE, ixekizumab; MS, multiple sclerosis; RIS, risankizumab; SECU, secukinumab; TIL, tildrakizumab; UST, ustekinumab. [Extracted from the article]

Tumour necrosis factor inhibitors (TNFis) are commonly used for treating psoriatic diseases; however, the risk of infection while receiving TNFis remains uncertain. The aim of this study was to investigate the infection risk in patients with psoriatic disease receiving TNFis. A prospectively registered systematic literature search was conducted in Medline (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and the ClinicalTrials.gov databases from inception to December 31, 2021. We included double‐blind randomized controlled trials that compared TNFis or other biologics with placebo in adults with psoriasis or psoriatic arthritis. The primary outcomes included overall and serious infection risks, and secondary outcomes included upper respiratory infections and nasopharyngitis risks. The risk ratio of the dichotomous outcome was calculated using the Mantel–Haenszel method with random effects, and heterogeneity was assessed using Cochran's Q statistic and quantified using the I‐squared statistic. A total of 48 studies with 15 464 patients with psoriatic diseases were included. The meta‐analysis demonstrated a slightly increased overall infection risk (risk ratio = 1.09; 95% confidence interval, 1.02–1.15) but not serious infection risk (risk ratio = 0.95; 95% confidence interval, 0.61–1.49) among patients receiving TNFis. There were also no increased risks of upper respiratory infections (risk ratio = 1.10; 95% confidence interval, 0.94–1.28) or nasopharyngitis (risk ratio = 1.14; 95% confidence interval, 1.00–1.30). In subgroup analyses using the fixed effects model, only etanercept and certolizumab pegol were, respectively, associated with an increased risk of overall infection (RR = 1.14, 95% CI, 1.03–1.27) and upper respiratory infections (RR = 1.42, 95% CI, 1.02–1.98). In conclusion, evidence to date suggests an increased overall infection risk that is generally tolerable in patients with psoriatic diseases receiving TNFis. There are no increased risks of serious infections, upper respiratory infections or nasopharyngitis. [ABSTRACT FROM AUTHOR]

We previously identified a chemotherapy-induced paracrine inflammatory loop that paradoxically mitigates the anti-tumor effect of chemotherapy and triggers metastatic propagation in breast and lung cancer models. Therefore, we sought to further validate and translate these findings into patient care by coupling the anti-TNF-α drug certolizumab pegol with standard cisplatin doublet chemotherapy. Here we first validate the anti-metastatic effect of certolizumab in a liver-metastatic Lewis Lung Carcinoma model. We then evaluate the safety, efficacy, and pharmacodynamic effects of certolizumab with cisplatin and pemetrexed in an open label Phase 1 clinical trial (NCT02120807) of eighteen adult patients with stage IV lung adenocarcinomas. The primary outcome is maximum tolerated dose. Secondary outcomes are response rate and progression-free survival (PFS); pharmacodynamic changes in blood and tumor are evaluated as a correlative outcome. There were nine partial responses among 16 patients evaluable (56%, 95% CI 30 to 80%). The median duration of response was 9.0 months (range 5.9 to 42.6 months) and median PFS was 7.1 months (95% CI 6.3 to NR). The standard 400 mg dose of certolizumab, added to cisplatin and pemetrexed, is well-tolerated and, as a correlative endpoint, demonstrates potent pharmacodynamic inhibition of peripheral cytokines associated with the paracrine inflammatory loop. Generation of TNF-α in response to chemotherapy has been associated with chemo-resistance and metastasis propagation. Here the authors show that the combination of an anti-TNF antibody and cisplatin doublet chemotherapy increases anti-tumor efficacy in lung cancer preclinical models and report the results of a phase I clinical trial of the anti-TNF-α antibody certolizumab in combination with chemotherapy in patients with stage IV lung adenocarcinomas. [ABSTRACT FROM AUTHOR]

The prevention of joint deformity is among the most important treatment goals of psoriatic arthritis. Some biologics disease-modifying antirheumatic drugs (bDMARDs) have been demonstrated to be effective for both the skin and joints, as well as for slowing radiographic progression. However, there has been a lack of direct comparisons of bDMARDs. To evaluate the comparative effects of bDMARDs in preventing radiographic progression in psoriatic arthritis, we conducted a systematic review and network meta-analysis. On March 7 2022, a search for relevant randomized trials was conducted on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Our outcomes included radiographic non-progression, a mean change in the total radiographic score, and adverse events leading to discontinuation (DAE) at week 24. We included 11 trials on 10 bDMARDs, involving 4010 participants. Most bDMARDs were more effective than placebos in achieving radiographic non-progression, including adalimumab (odds ratio (OR) 4.7, 95% confidence interval (CI) 2.66–8.29), etanercept (OR 4.19, 95% CI 1.65–10.61), certolizumab pegol (OR 2.83, 95% CI 1.55–5.2), secukinumab 300 mg (OR 2.63, CI 1.62–4.27), infliximab (OR 2.54, CI 1.13–5.69), ixekizumab (OR 2.22, 95% CI 1.06–4.65), golimumab (OR 2.21, 95% CI 1.24–3.93), and abatacept (OR 1.54, 95% CI 1.03–2.28). A significant reduction in the total radiographic score was found in infliximab (standardized mean difference (SMD) −0.59, 95% CI −0.87, −0.3), etanercept (SMD −0.51, 95% CI −0.78, −0.23), adalimumab (SMD −0.45, 95% CI −0.64, −0.26), ixekizumab (SMD −0.37, 95% CI −0.62, −0.12), secukinumab 300 mg (SMD −0.33, 95% CI −0.50, −0.15), golimumab (SMD −0.33, 95% CI −0.58, −0.09), secukinumab 150 mg (SMD −0.25, 95% CI −0.43, −0.07), certolizumab pegol (SMD −0.23, 95% CI −0.44, −0.03), and ustekinumab (SMD −0.19, 95% CI −0.35, −0.33). No significant differences in DAE were detected between bDMARDs. In conclusion, anti-tumor necrosis factor agents (adalimumab, infliximab, and etanercept) may be preferred for treating psoriatic arthritis for their superiority in preventing radiographic progression. [ABSTRACT FROM AUTHOR]

Patients requiring systemic therapies have extensive skin involvement, significant impact on functioning or QOL, and disease in sensitive areas and/or they are refractory to topical therapies. Undertreatment, treatment trends, and treatment dissatisfaction among patients with psoriasis and psoriatic arthritis in the United States: Findings from the National Psoriasis Foundation (NPF) surveys, 2003-2011. Narrowband UVB (NB-UVB) is the preferred phototherapy regimen for most patients with generalized psoriasis, whereas targeted phototherapy with an excimer laser is appropriate for patients with localized disease. ABBREVIATIONS IN THIS FEATURE AAD American Academy of Dermatology ACR American College of Rheumatology BAD British Association of Dermatologists BB-UVA Broadband UVA BSA Body surface area DLQI Dermatology Life Quality Index IBD Inflammatory bowel disease NB-UVB Narrowband UVB NPF National Psoriasis Foundation PASI Psoriasis Area Severity Index PGA Physician Global Assessment PsA Psoriatic arthritis PUVA Psoralen plus UVA QOL Quality of life TCI Topical calcineurin inhibitor TCS Topical corticosteroid TNF Tumor necrosis factor SESSION OVERVIEW PSAP in JACCP features are developed from activities presented as part of the Pharmacotherapy Self-Assessment Program (PSAP). [Extracted from the article]

Axial spondyloarthritis (axSpA) is an immune-mediated inflammatory disease that affects predominantly the sacroiliac joints and spine. The main goal of axSpA therapy is to slow down and prevent structural damages that become a main cause of disability in able-bodied patients. Timely diagnosis and early prescription of biological agents can slow down the progression of the disease. The paper presents the experience in using the tumor necrosis factor-α inhibitor certolizumab pegol (CP) in a young female patient with early axSpA, who receives the drug within the framework of a model for clinical statistical groups (CSG) in the Kaliningrad Region. The high efficiency of CP and the possibility of using the latter within the CSG tariffs allow the drug to be prescribed for early-stage axSpA. The absence of an Fc-fragment in the molecular structure of CP provides additional opportunities for reproductive-aged female patients who can use the drug during the planning stage, pregnancy, and lactation.

We present a case of certolizumab-associated renal sarcoidosis, the first reported case in a patient with psoriatic arthritis (PsA) that was effectively treated with corticosteroids. A 55-year-old Caucasian man with PsA diagnosed at age 47 and plaque psoriasis since his early twenties was on certolizumab pegol (CZP) for 7 months before presenting to the emergency department with seizures and renal failure. A renal biopsy confirmed renal sarcoidosis. His CZP therapy was stopped, and after several months taking prednisolone at a reducing regime, his renal function improved, and his PsA remained under control. When considering further treatment options for his PsA keeping in mind that other drugs, especially tumour necrosis factor-alpha inhibitors, have been reported to be associated with sarcoidosis, tofacitinib was considered to be a future treatment option acceptable to the patient, given current National Institute for Health and Care Excellence guidelines approving its use in PsA and the lack of reports of tofacitinib-associated sarcoidosis in the literature. [ABSTRACT FROM AUTHOR]

Pegylation of biopharmaceuticals is the most common strategy to increase their half-life in the blood and is associated with a reduced immunogenicity. As antigen presentation is a primary event in the activation of CD4 T-cells and initiation of Anti-Drug Antibody (ADA) response, we investigated the role of the PEG molecule on the T-cell reactivity of certolizumab pegol (CZP), a pegylated anti-TNFα Fab. We generated T-cell lines raised against CZP and its non-pegylated form (CZNP) and demonstrated CZP primed few T-cells in comparison to CZNP. CZP-primed lines from 3 donors responded to a total of 5 epitopes, while CZNP-primed lines from 3 donors responded to a total of 7 epitopes, 4 epitopes were recognized by both CZP- and CZNP-primed lines. In line with this difference of T-cell reactivity, CZP is less internalized by the dendritic cells than CZNP. In vitro digestion assay of CZP by Cathepsin B showed a rapid removal of the PEG moiety, suggesting a limited influence of PEG on CZP proteolysis. We therefore demonstrate that pegylation diminishes antigen capture by dendritic cells, peptide presentation to T-cells and T-cell priming. This mechanism might reduce immunogenicity and contribute to the long half-life of CZP and possibly of other pegylated molecules. [ABSTRACT FROM AUTHOR]

Coccidioides fungi are found primarily in the southwestern United States and are the cause of coccidioidomycosis. Tumor necrosis factor α inhibitors (TNFIs) are therapies for autoimmune and inflammatory conditions; their association with coccidioidomycosis is not well characterized. We aimed to determine the prevalence and characteristics of coccidioidomycosis among TNFI recipients with different inflammatory disorders at a tertiary care center. We retrospectively reviewed the electronic health records of patients at our institution from April 4, 2010 to December 17, 2017, who received TNFIs (infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab) and had positive culture, pathologic, and/or serologic results for coccidioidomycosis. Among 1770 patients identified who received TNFIs, 49 (2.8%) had proven or probable coccidioidomycosis. Of these 49, 28 (57%) were men, 47 (96%) were White, and 42 (86%) had pulmonary coccidioidomycosis. The most common TNFIs used were adalimumab, infliximab, and etanercept. Coccidioidomycosis was identified in 25 of 794 patients with rheumatologic disorders (3.1%), 18 of 783 patients with inflammatory bowel disease (IBD) (2.3%), and six of 193 patients with dermatologic disorders (3.1%) (P  = .34). There was no difference in coccidioidal infections among recipients of any particular TNFI agents. A minority of patients (7/49, 14%) had an extrapulmonary infection, and the majority of these (6/7) had IBD. Our study shows a low prevalence of coccidioidomycosis in TNFI recipients, even within the Coccidioides -endemic area. Persons with IBD were disproportionately represented among those with extrapulmonary coccidioidomycosis. Treatment with azoles was effective. Lay Summary Among 1770 patients who received tumor necrosis factor α inhibitors, 49 (2.8%) had newly acquired coccidioidomycosis over a 7-year period. Dissemination occurred in 14.3%, but disproportionately among those with underlying inflammatory bowel disease. All patients recovered with medical management. [ABSTRACT FROM AUTHOR]

Objectives The efficacy and safety of certolizumab pegol (CZP), an Fc-free, PEGylated anti-TNF, in axial spondyloarthritis (axSpA) has been established in clinical trial settings. We report CZP effectiveness and safety in European clinical practice in patients with axSpA, including radiographic (r-) and non-radiographic (nr-) axSpA. Methods CIMAX (NCT02354105), a European non-interventional multicentre prospective study, observed CZP treatment response and safety over 12 months in a real-world axSpA cohort. The primary outcome was change from baseline in BASDAI to week 52, with additional outcomes pertaining to effectiveness and safety. Patients who received ≥1 dose CZP were followed up for adverse events, and those with baseline and ≥1 post-baseline BASDAI assessment were included in effectiveness analyses. Results A total of 672 patients (r-axSpA: 469; nr-axSpA: 201; unconfirmed diagnosis: 2) from 101 sites received ≥1 dose of CZP, of whom 564 (r-axSpA: 384; nr-axSpA: 179; unconfirmed: 1) were included in the effectiveness analyses. The mean baseline BASDAI was 6.1 in the overall axSpA population and r-axSpA and nr-axSpA subpopulations. At week 52, the mean (s. d.) change in BASDAI was −2.9 (2.3; n  = 439); for r-axSpA and nr-axSpA, it was −2.9 (2.2; n  = 301) and −2.8 (2.4; n  = 137), respectively (P  <0.0001 for all). Similar improvements were seen across other axSpA disease measures. In total, 37.9% (255/672) patients experienced adverse events, and 1.8% (12/672) experienced ≥1 serious adverse events. Conclusion Improvements observed in signs and symptoms of axSpA following one year of CZP treatment in real-world clinical practice were similar to those from previous randomized clinical trials, with no new safety concerns. [ABSTRACT FROM AUTHOR]

What is known and objective: Tumour necrosis factor‐α–blocking agents potentially cause vasculitis. However, no study has reported on the association between hypocomplementemic urticarial vasculitis (HUV) and certolizumab pegol (CZP) usage. Case description: We present the first case of HUV development during CZP treatment for rheumatoid arthritis. Hypocomplementemic urticarial vasculitis improved after CZP was discontinued and the dose of oral prednisolone was increased. What is new and conclusion: Clinicians should be aware about the potential development of HUV during CZP treatment, which is presumed to be safe considering its unique structural characteristics that differ from those of other tumour necrosis factor‐α–blocking agents. [ABSTRACT FROM AUTHOR]