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Abstract Background The role of cytomegalovirus infection as an opportunistic pathogen in exacerbating ulcerative colitis and its response to treatment remain a topic of ongoing debate. Clinicians encounter numerous challenges, including the criteria for differentiating between an acute ulcerative colitis flare and true cytomegalovirus colitis, the diagnostic tests for identifying cytomegalovirus colitis, and determining the appropriate timing for initiating antiviral therapy. Case presentation A 28-year-old Syrian female with a seven-year history of pancolitis presented with worsening bloody diarrhea, abdominal pain, and tenesmus despite ongoing treatment with azathioprine, mesalazine, and prednisolone. She experienced a new flare of acute severe ulcerative colitis despite recently completing two induction doses of infliximab (5 mg/kg) initiated four weeks prior for moderate-to-severe ulcerative colitis. She had no prior surgical history. Her symptoms included watery, bloody diarrhea occurring nine to ten times per day, abdominal pain, and tenesmus. Initial laboratory tests indicated anemia, leukocytosis, elevated C-reactive protein (CRP) and fecal calprotectin levels, and positive CMV IgG. Stool cultures, Clostridium difficile toxin, testing for Escherichia coli and Cryptosporidium, and microscopy for ova and parasites were all negative. Sigmoidoscopy revealed numerous prominent erythematous area with spontaneous bleeding. Biopsies demonstrated CMV inclusions confirmed by immunohistochemistry, although prior biopsies were negative. We tapered prednisolone and azathioprine and initiated ganciclovir at 5 mg/kg for ten days, followed by valganciclovir at 450 mg twice daily for three weeks. After one month, she showed marked improvement, with CRP and fecal calprotectin levels returning to normal. She scored one point on the partial Mayo score. The third induction dose of infliximab was administered on schedule, and azathioprine was resumed. Conclusion Concurrent cytomegalovirus infection in patients with inflammatory bowel disease presents a significant clinical challenge due to its associated morbidity and mortality. Diagnosing and managing this condition is particularly difficult, especially regarding the initiation or continuation of immunosuppressive therapies.

Background: The role of cytomegalovirus infection as an opportunistic pathogen in exacerbating ulcerative colitis and its response to treatment remain a topic of ongoing debate. Clinicians encounter numerous challenges, including the criteria for differentiating between an acute ulcerative colitis flare and true cytomegalovirus colitis, the diagnostic tests for identifying cytomegalovirus colitis, and determining the appropriate timing for initiating antiviral therapy. Case presentation: A 28-year-old Syrian female with a seven-year history of pancolitis presented with worsening bloody diarrhea, abdominal pain, and tenesmus despite ongoing treatment with azathioprine, mesalazine, and prednisolone. She experienced a new flare of acute severe ulcerative colitis despite recently completing two induction doses of infliximab (5 mg/kg) initiated four weeks prior for moderate-to-severe ulcerative colitis. She had no prior surgical history. Her symptoms included watery, bloody diarrhea occurring nine to ten times per day, abdominal pain, and tenesmus. Initial laboratory tests indicated anemia, leukocytosis, elevated C-reactive protein (CRP) and fecal calprotectin levels, and positive CMV IgG. Stool cultures, Clostridium difficile toxin, testing for Escherichia coli and Cryptosporidium, and microscopy for ova and parasites were all negative. Sigmoidoscopy revealed numerous prominent erythematous area with spontaneous bleeding. Biopsies demonstrated CMV inclusions confirmed by immunohistochemistry, although prior biopsies were negative. We tapered prednisolone and azathioprine and initiated ganciclovir at 5 mg/kg for ten days, followed by valganciclovir at 450 mg twice daily for three weeks. After one month, she showed marked improvement, with CRP and fecal calprotectin levels returning to normal. She scored one point on the partial Mayo score. The third induction dose of infliximab was administered on schedule, and azathioprine was resumed. Conclusion: Concurrent cytomegalovirus infection in patients with inflammatory bowel disease presents a significant clinical challenge due to its associated morbidity and mortality. Diagnosing and managing this condition is particularly difficult, especially regarding the initiation or continuation of immunosuppressive therapies. [ABSTRACT FROM AUTHOR]

The introduction of anti-tumor necrosis factor α (TNFα) biologics significantly innovated inflammatory bowel disease (IBD) treatment and increased medical costs. The recent expiration of patents of some anti-TNFα biologics (such as infliximab and adalimumab) facilitated the development of biosimilars. Comparable pharmacokinetic, efficacy, safety, and immunogenicity profiles between anti-TNFα originators and biosimilars were demonstrated in different studies. Anti-TNFα biosimilars hold promise for reducing the high cost of biologics and increasing patient access to biologics. In this review, we outline the current data on the use of anti-TNFα originators and biosimilars in patients with IBD, with a focus on the efficacy, safety, and immunogenicity profiles of infliximab and adalimumab biosimilars. The potential benefits, challenges, and future directions of anti-TNFα biosimilars are also discussed in the review. [ABSTRACT FROM AUTHOR]

Background: The risk of developing non-melanoma skin cancers (NMSCs) in patients with psoriasis is highly debated, and, to date, there is no unambiguous consensus opinion. Psoriasis is known to be related to an increased likelihood of other comorbidities such as psoriatic arthritis, obesity, metabolic syndrome, depression, and cardiovascular disease. Regarding cancer risk, previous studies have reported a greater tendency for the development of cutaneous T-lymphomas and colon, breast, kidney, and lung cancers. Furthermore, data from network meta-analyses have shown that patients with psoriasis have a higher risk of developing squamous cell carcinomas (SCCs) and/or basal cell carcinomas (BCCs). Multiple factors may contribute to the development of NMSCs in psoriatic patients, ranging from immunosuppression induced by biologic agents to previous phototherapy. However, the extent to which each factor may impact this risk has not been entirely assessed. The aim of this study was to evaluate the risk of developing NMSCs in patients with psoriasis observed for at least 5 years, by directly comparing patients only treated with phototherapy and patients treated with anti-tumor necrosis factor α (TNFα) agents, naive to other systemic treatments or phototherapy. Methods: We conducted a single-center retrospective study at Siena University Hospital, Italy, on 200 adult patients with psoriasis divided into two groups: (i) group 1, including 100 patients treated with narrow-band UVB phototherapy (nb-UVB), and (ii) group 2, including 100 patients treated with anti-TNFα. The patients included in group 2 had to be naive to cDMARDs and biologics and treated with anti-TNFα continuously for 5 years without loss of efficacy. All patients were observed for 5 years and underwent annual dermatologic examinations to assess for the occurrence of BCC or SCC. Results: A total of 34 out of 100 patients treated with phototherapy had one BCC or one SCC and 10 out of 34 developed two skin cancers. In particular, five had both types (one BCC and one SCC), and five had two BCCs. Conclusions: The results of our study highlight how the risk of developing NMSCs is greater in patients undergoing phototherapy compared to those treated with anti-TNFα. It also draws attention to the consideration that patients with scalp psoriasis might need closer follow-up as they could be more at risk of developing NMSCs. [ABSTRACT FROM AUTHOR]

In patients with ulcerative colitis (UC), the development of an antidrug antibody (ADA) to anti-tumor necrosis factor (TNF)α agent is a crucial problem which aggravates the clinical course of the disease, being cited as one of the most common causes for discontinuing anti-TNFα treatment. This is due to ADA eventually causing secondary LOR, leading to discontinuation of anti-TNFα treatment. Recently, research on the microbiome and relationship between worsening UC and dysbiosis has been conducted. Further, investigations on the association between the microbiome and secondary LOR are increasing. Here, we present the therapeutic effect of fecal microbiota transplantation (FMT) on a 42-year-old man with secondary LOR and high ADA levels. FMT has recently been used for the treatment of, and for overcoming, drug resistance through microbiome modification. Stool samples were collected from the patient before and 4 weeks after FMT. Symptoms, including hematochezia and Mayo endoscopy sub-scores, improved after FMT, while ADA levels decreased by one-third to less than half the value (29 ng/mL) compared to before FMT (79 ng/mL). Additionally, the trough level of infliximab became measurable, which reflects the improvement in the area under the concentration (AUC). Butyricicoccus, Faecalibacterium, Bifidobacterium, Ligilactobacillus, Alistipes, and Odoribacter, which regulate immune responses and alleviate inflammation, also increased after FMT. We report a case in which microbiome modification by FMT increased the AUC of anti-TNFα in a patient who developed secondary LOR during anti-TNFα treatment, thereby improving symptoms and mucosal inflammation. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Yet, the description of a polymorphic cell infiltration in LN biopsy, the absence of clinical lymphadenopathy at presentation, the history of psoriatic arthritis as well as the preceded treatment with anti-tumor necrosis factor (TNF)- and cyclosporine raised diagnostic concerns. Although the patient could not finally avoid R-CHOP immunochemotherapy, this case highlights that a trial of NBA withdrawal under very close monitoring could be a rational therapeutic choice even in patients with aggressive ID-LPDs. Keywords: diffuse large B-cell lymphoma; psoriasis; infliximab; apremilast; novel biologic agent; anti-TNF EN diffuse large B-cell lymphoma psoriasis infliximab apremilast novel biologic agent anti-TNF 1695 1700 6 10/12/23 20231001 NES 231001 The association of psoriasis with cancer has been a matter of debate, especially in the era of the novel biologic agents (NBA). Lastly, taking into consideration our case with the re-appearance of the lymphoma despite the change of NBA as well as all the other cases described in Table 1, the appearance of LPDs in psoriatic patients is a more complex process influenced by clinical disease duration and extension, the time length of immunosuppression and the nature of the various treatments administered. [Extracted from the article]

Abstract Objective To evaluate the impact of anti-tumor necrosis factor-alpha (TNFα: etanercept [Etanercept ®]) therapy on adrenal activity in juvenile idiopathic arthritis (JIA) . Method Eleven JIA patients aged 12 ± 6.2 years with a disease duration of 6.3 ± 5.2 years were enrolled. They were treated once weekly with etanercept (0.8 mg/kg) for 3 ± 2.8 years. Urine samples for gas chromatography-mass spectrometry steroid hormone analysis were collected before, and 1 and 3 days after etanercept injection and compared to age- and sex-matched healthy controls. Results The levels of 21 of the 31 metabolites were low before etanercept treatment. Those 21 metabolites included 4 C19 steroids (androgens), 5 C C21 steroid hormone intermediates, 10 cortisol metabolites, and 2 corticosterone metabolites. One day after treatment, only 5 of the 21 metabolite levels remained low. They included 2 C19 metabolites, 2 C21 steroid metabolites and 1 cortisol metabolite β –Cortol (β-Cl). Three days after treatment, the only metabolites levels that continued to be low were 2 C19 metabolite, 2 C21 steroid hormone intermediates and 1 cortisol metabolite α-Cortol (a-Cl), while the remaining 15 metabolites had already normalized after 1 day. Dehydroepiandrosterone-sulfate and 17-hydroxypregnenolone metabolite levels were the last ones to recover. Urinary metabolite ratios reflecting cytochrome P450 CYP21A2 (21-hydroxylase) and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzymatic activitieswere lower in JIA patients than in controls, although significant was not reached. Conclusion Almost all of the pre-etanercept treatment cortisol urinary metabolite levels were significantly lower than normal, and almost all rose to normal values by 1 day after treatment. The therapeutic effect of anti-TNFα treatment in JIA may be related to its effect on the restoration of adrenal function and cortisol levels.

Drug-induced lupus erythematosus is an autoimmune disease with unexpected onset after treatment with certain drugs. Clinically, this disease is very similar to idiopathic lupus erythematosus, although its manifestations are typically milder. In addition, the laboratory and histological changes of the induced forms are also not significantly different from the idiopathic condition, sometimes making the diagnosis of the drug-induced form a challenge for clinicians. This entity has been gaining relevance in the clinical setting and the number of drugs associated with it has been increasing, mainly due to the emergence of new biological therapies with a strong causal link with drug-induced lupus, such as tumor necrosis factor-alpha inhibitors. However, there are still no universally accepted diagnostic criteria to identify this disease, and information about its pathophysiology is still somewhat scarce, making it difficult to predict the most likely culprit drugs before there are enough reports to establish a strong link. In addition, although some risk factors have shown susceptibility for certain individuals, they are not yet fully understood. Given the possibility of disease reversal by the withdrawal of the offending drug, it is extremely important to be aware of the possible implication of a drug in the pathogenesis of this disease, and for clinicians who approach patients with lupus manifestations, particularly cutaneous manifestations, it is mandatory to look for the onset of new drugs used by the patient. This review will systematize the current knowledge about this drug-induced lupus, in terms of pathophysiology, clinical, histopathological, and laboratory manifestations, diagnosis, and treatment, as well as the most commonly implicated drugs. [ABSTRACT FROM AUTHOR]

Vaccines are pivotal for control of the coronavirus disease (COVID-19) pandemic. Patients with inflammatory bowel diseases (IBDs) treated with antitumor necrosis factor (TNF)-α have lower serologic response after two COVID-19 vaccine doses. Data regarding a third vaccine dose are scarce. An Israeli multicenter prospective observational study recruited 319 subjects: 220 with IBD (79 treated with anti-TNFα) and 99 healthy control (HC) participants. All patients received two mRNA-BNT162b2 vaccines (Pfizer/BioNTech), 80% of whom received a third vaccine dose. Evaluation included disease activity, anti-spike (S) and nucleocapsid (N) antibody levels, anti-TNFα drug levels, and adverse events (AEs). All participants showed significant serologic response one month after receiving a third dose. However, three months later, the anti-S levels decreased significantly in patients treated with anti-TNFα compared with the non-anti-TNFα and HC groups. A correlation between serologic response to the third vaccine dose and anti-TNF drug levels was not found. No significant AE or IBD exacerbation was observed. Importantly, lower serologic response after the third vaccine dose predicted infection. A third dose of BNT162b2 is effective and safe in patients with IBD. Lower serologic response predicted infection, even in seropositive subjects. Lower serologic responses and their rapid decline suggest a fourth vaccine dose in this patient population. [ABSTRACT FROM AUTHOR]

In patients with ulcerative colitis (UC), the development of an antidrug antibody (ADA) to anti-tumor necrosis factor (TNF)α agent is a crucial problem which aggravates the clinical course of the disease, being cited as one of the most common causes for discontinuing anti-TNFα treatment. This is due to ADA eventually causing secondary LOR, leading to discontinuation of anti-TNFα treatment. Recently, research on the microbiome and relationship between worsening UC and dysbiosis has been conducted. Further, investigations on the association between the microbiome and secondary LOR are increasing. Here, we present the therapeutic effect of fecal microbiota transplantation (FMT) on a 42-year-old man with secondary LOR and high ADA levels. FMT has recently been used for the treatment of, and for overcoming, drug resistance through microbiome modification. Stool samples were collected from the patient before and 4 weeks after FMT. Symptoms, including hematochezia and Mayo endoscopy sub-scores, improved after FMT, while ADA levels decreased by one-third to less than half the value (29 ng/mL) compared to before FMT (79 ng/mL). Additionally, the trough level of infliximab became measurable, which reflects the improvement in the area under the concentration (AUC). Butyricicoccus, Faecalibacterium, Bifidobacterium, Ligilactobacillus, Alistipes, and Odoribacter, which regulate immune responses and alleviate inflammation, also increased after FMT. We report a case in which microbiome modification by FMT increased the AUC of anti-TNFα in a patient who developed secondary LOR during anti-TNFα treatment, thereby improving symptoms and mucosal inflammation.

Copyright of Pediatric Rheumatology is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study aimed to evaluate the efficacy of secukinumab (SEC) in axial spondyloarthropathy (axSpA) in anti-TNFα naïve and anti-TNFα experienced patients. It also focused on the duration of SEC treatment and its side effects. The patients with axSpA treated with SEC and followed up in our outpatient clinic from May 2018 through October 2021 were included in this study. All patients in the study also fulfilled the ASAS classification criteria for axSpA. Patients were separated into two groups according to whether they received prior anti-TNFα therapy. While anti-TNFα naïve patients comprised group 1, anti-TNFα experienced patients were included in group 2. Pre- and post-treatment BASDAI scores were reported and compared. Eighty-four axSpA patients (42 men; duration of the disease: 86.86 ± 65.35 months in group 1 and 160.65 ± 97.4 months in group 2) were treated with SEC. 45.5% of anti-TNFα naïve patients and 56.5% of anti-TNFα experienced patients were still on SEC therapy in October 2021. Duration of SEC treatment was 12.5 ± 7.9 months in group 1 and 17.19 ± 12 months in group 2 (p = 0.098). The differences between pre-and post-treatment BASDAI scores were statistically significant in both groups (p < 0.001). While patients in group 1 did not develop any adverse effects, three patients in group 2 experienced alopecia, uveitis, and recurrent pneumonia after SEC treatment. Our study's efficacy and safety data on the use of SEC were reassuring in both anti-TNFα naïve and anti-TNFα experienced patients. However, further studies are still needed to determine the appropriate timing to begin SEC treatment. [ABSTRACT FROM AUTHOR]

La neurosarcoïdose est une manifestation rare mais potentiellement grave de la sarcoïdose, associée à une morbidité et mortalité significatives. Dans les différentes études, la mortalité était d'environ 10 % à 10 ans avec plus de 30 % des patients qui avaient un handicap significatif à la fin du suivi. Les atteintes les plus fréquentes sont les atteintes encéphaliques (50–60 %) avec en particulier une atteinte des paires crâniennes (nerfs VII le plus fréquemment puis nerfs optiques, oculomoteurs et vestibulaire), médullaires (20–30 %) et plus rarement du système nerveux périphérique (10–15 % environ). Tout l'enjeu du diagnostic est d'éliminer les diagnostics différentiels. Les présentations atypiques peuvent faire discuter la nécessité de biopsie cérébrale afin de mettre en évidence la présence de lésions granulomateuses tout en éliminant les diagnostics alternatifs notamment infectieux et tumoraux. La prise en charge thérapeutique repose sur la corticothérapie et les immunomodulateurs. Il n'y a pas d'étude prospective comparative permettant de statuer clairement sur le choix de l'immunosuppresseur en première intention et dans les formes réfractaires. Les immunosuppresseurs conventionnels tels que le méthotrexate, le mycophénolate mofétil et le cyclophosphamide sont couramment employés. Les données sont de plus en plus nombreuses sur l'utilisation des anti-TNFα (notamment l'infliximab) dans les formes réfractaires et/ou sévères. Des données supplémentaires sont nécessaires pour évaluer leur intérêt en première ligne chez les patients ayant une atteinte sévère et associée à un risque non négligeable de rechute. Neurosarcoidosis (NS) is a rare but severe form of sarcoidosis. NS is associated with significant morbidity and mortality. Mortality is about 10% at 10 years with more than 30% of patients who have a significant disability. The most frequent features are cranial neuropathy (the facial and optic nerve most commonly affected), cranial parenchymal lesions, meningitis, spinal corn abnormalities (20–30%) and more rarely peripheral neuropathy (approximately 10–15%). The challenge of diagnosis is to eliminate other diagnoses. Atypical presentations should make to discuss the need for cerebral biopsy in order to highlight the presence of granulomatous lesions while eliminating alternative diagnosis. Therapeutic management is based on corticosteroid therapy and immunomodulators. There are no comparative prospective study to allow us to define the first-line immunosuppressive treatment and the therapeutic strategy in refractory patients. Conventional immunosuppressants such as methotrexate, mycophenolate mofetil and cyclophosphamide are commonly used. Data on the efficacy of anti-TNFα (including infliximab) in refractory and/or severe forms are increasing during the last ten years. Additional data is necessary to assess their interest in first line in patients with severe involvement and a significant risk of relapse. [ABSTRACT FROM AUTHOR]

Simple Summary: The management and treatment of patients with inflammatory bowel diseases after a diagnosis of malignancy represents a challenge for physicians, since their most common therapy, such as biologics and immunosuppressants, should be discontinued for 2–5 years after the end of cancer treatment. Special situations could be managed using new gut-selective drugs; however, limited data are available for these new therapies. We aim to summarize the current evidence about the reintroduction of different therapies after the primary diagnosis of cancer and to describe the course of inflammatory bowel disease without any immunosuppressive treatment after the diagnosis of cancer. Patients with chronic inflammatory bowel diseases (IBD) have increased risk of developing intestinal and extraintestinal cancers. However, once a diagnosis of malignancy is made, the therapeutic management of Crohn's disease (CD) and ulcerative colitis (UC) can be challenging as major guidelines suggest discontinuing the ongoing immunosuppressant and biological therapies for at least 2–5 years after the end of cancer treatment. Recently, new molecules such as vedolizumab and ustekinumab have been approved for IBD and limited data exist on the real risk of new or recurrent cancer in IBD patients with prior cancer, exposed to immunosuppressants and biologic agents. Thus, a multidisciplinary approach and case-by-case management is the preferred choice. The primary aim of our review was to summarize the current evidence about the safety of reintroducing an immunosuppressant or biologic agent in patients with a history of malignancy and to compare the different available therapies, including gut-selective agents. The secondary aim was to evaluate the clinical course of the IBD patients under cancer treatment who do not receive any specific immunosuppressant treatment after the diagnosis of cancer. [ABSTRACT FROM AUTHOR]

Background Budesonide remains the backbone therapy for microscopic colitis [MC]; however, relapses are frequent, and some patients are intolerant or dependent. Anti-TNF therapy is increasingly used to treat these patients, but available evidence is still limited. The aim of this study was to evaluate the effectiveness and safety of anti-TNF therapy in MC patients failing budesonide. Methods In a multicentre retrospective cohort study, budesonide-refractory, -dependent, or -intolerant MC patients treated with anti-TNF agents were included. Clinical remission was defined as fewer than three bowel movements per day, and clinical response was defined as an improvement in stool frequency of at least 50%. Results Fourteen patients were included. Median age was 58.5 years, median disease duration was 25 months, and median follow-up was 29.5 months. Seven patients were treated with infliximab [IFX], and seven with adalimumab. Clinical remission without steroids at 12 weeks was reached in 5/14 [35.7%] patients; all of these received IFX. Clinical response at 12 and 52 weeks, was obtained in 9/14 [64.3%] and 7/14 [50%] patients, respectively. Five patients switched to another anti-TNF agent. When considering both first- and second-line anti-TNF therapies, 7 [50%] patients were in clinical remission at Week 52. Mild to moderate adverse events were reported in six ptients. Two patients were treated with vedolizumab, of whom one had clinical response; one patient treated with ustekinumab had no response. Conclusions This is the first multicentre cohort study showing that half of patients treated with anti-TNF therapy for MC achieved clinical remission in case of budesonide failure. [ABSTRACT FROM AUTHOR]

Abstract Background ABP501 is a biosimilar to Reference Adalimumab (HUMIRA®) produced by AMGEN. Adalimumab (ADA) has a marketing authorization for Crohn's disease, ulcerative colitis and other inflammatory or autoimmune diseases. The aim of this study was to evaluate the LISA-TRACKER assays developed by Theradiag (France), for the monitoring of ABP501 and anti-ABP501 antibodies in human serum. Results 68 ABP501 clinical samples were measured with the LISA TRACKER Duo Adalimumab assay. LISA TRACKER has been validated as suitable for quantification of ABP501 in human serum samples. Accuracy of the LISA-TRACKER was measured using 3 human serum matrices spiked with known levels of biosimilar, 3 levels spanning the dynamic range. Percentages of recovery were ranged from 90 to 120% for biosimilar batch1, and between 93 and 105% for biosimilar batch2. The acceptance criteria (CV 50% for specificity. Specificity was tested with Biosimilar spiked samples, Biosimilar with Humira® spiked samples, and clinical samples from patients treated with adalimumab biosimilar. All of these samples were spiked with polyclonal antibodies directed against Humira®. Specificity inhibition and specificity detection steps were also part of the validation parameters. Reagents made with ABP501 gave similar results than reagents made with Humira® meeting acceptance criteria. Conclusions LISA-TRACKER ADA and anti-ADA assays are reliable for the monitoring of patients treated with ABP501.

Cytokine patterns and immune activation in patients with Coronavirus 2019 (COVID-19) seem to resemble the case of rheumatoid arthritis (RA), psoriasis and inflammatory bowel disease (IBD). Biological drugs, such as anti-tumor necrosis factor α (TNFα) and interleukin (IL) inhibitors, appear to be protective against adverse outcomes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). However, these treatments are associated with an increased risk of secondary infections. The aim of the study was to examine the association between the use of immunomodulatory drugs and the risk of SARS-CoV-2-associated positivity, hospitalization and death compared to other commonly prescribed treatment regimens among patients with immune-mediated inflammatory diseases. Methods: All patients with RA, Psoriasis and IBD were included in this observational analysis and treated with anti-TNFα, IL-inhibitors, Methotrexate (MTX) and Sulfasalazine drugs during the year 2020–2021. The population consisted of 932 patients and demographic, clinical and pharmacological data were analyzed. Results: Although no significant differences were observed between patients treated with biological and synthetic drugs in terms of hospitalization and death, the multivariate logistic model showed that the type of drug influences the possibility of COVID-19 positivity. Conclusions: The results of this analysis support the use of biological drugs and justify further research investigating the association of these biological therapies with COVID-19 outcomes. [ABSTRACT FROM AUTHOR]

Background: Patients living with HIV (PLWHIV) can develop autoimmune diseases (AD) needing immunosuppressive treatments (IST). This study aims to describe the impact of IST in PLWHIV. Methods: This was a multicentric retrospective observational study in six HIV referral centers on PLWHIV under IST for AD. Demographic factors, viral co-infections, immunovirological status before and under IST, infectious events, and their descriptions were collected and described focusing on infectious events, immunovirological variations, and IST effectiveness. Results: 9480 PLWHIV were screened for inclusion. Among them, 138 (1.5%) had a history of auto-immune disease, among which 32 (23%) received IST. There was mainly spondyloarthropathy (28%) and the most commonly used IST was methotrexate. The median follow-up under IST was 3.8 years (2.7; 5.9). There were 15 infectious events (0.5 events/individuals) concerning nine patients. At the last medical follow-up, 81% of these were in remission of their AD. Under IST, there was an increase in CD4 during follow-up (629 vs. 827 CD4/mm3, p = 0.04). No HIV virological failure was noted. Conclusions: This study supports a growing evidence base that IST can be used safely and effectively in PLWHIV with careful monitoring. [ABSTRACT FROM AUTHOR]

The efficacy of the COVID-19 mRNA vaccine, including the third vaccination in pediatric inflammatory bowel disease (PIBD) patients is not fully understood. This study aimed to evaluate the humoral immunogenicity of the BNT162b2 vaccine and the changes in durability until 20–28 weeks after the initial vaccine series in PIBD patients on immunosuppressive drugs. The safety of the initial vaccine series and the booster effect of the third vaccination were also evaluated. A single-center, prospective cohort study was conducted, and 63 participants (anti-TNFα: 11; non-anti-TNFα: 31; 5-ASA: 21), with a mean age of 15.2 (range 9.6–17.9) years, were enrolled. All PIBD patients were seroconverted, with no serious short-term AEs. PIBD patients on anti-TNFα had significantly lower antibody titers than those on other medications at all measurement points. Furthermore, antibody titers waned over time with anti-TNFα and were significantly lower at 20–28 weeks than at 3–9 weeks after a two-vaccine series. In all 10 patients (anti-TNFα: 5; non-anti-TNFα including 5-ASA: 5), the third vaccination led to antibody concentrations significantly higher than those at the same time point after the second vaccination. PIBD patients on anti-TNFα need to remain vigilant about COVID-19 even after two vaccinations, and a third vaccination may be considered. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic systemic inflammatory disease associated with a higher incidence of cardiovascular disease, especially in patients with moderate to severe psoriasis. It has been estimated that severe psoriasis confers a 25% increase in relative risk of cardiovascular disease, regardless of traditional risk factors. Although the underlying pathogenic mechanisms relating psoriasis to increased cardiovascular risk are not clear, atherosclerosis is emerging as a possible link between skin and vascular affection. The hypothesis that the inflammatory cascade activated in psoriasis contributes to the atherosclerotic process provides the underlying basis to suggest that an anti-inflammatory therapy that improved atherosclerosis would also reduce the risk of MACEs. In this sense, the introduction of biological drugs which specifically target cytokines implicated in the inflammatory cascade have increased the expectations of control over the cardiovascular comorbidity present in psoriasis patients, however, their role in vascular damage processes remains controversial. The aim of this paper is to review the mechanistic link between psoriasis and cardiovascular disease development, as well as analyzing which of the biological treatments could also reduce the cardiovascular risk in these patients, fueling a growing debate on the modification of the general algorithm of treatment. [ABSTRACT FROM AUTHOR]

Marta Ko&lstrok;t-Kami&nacute;ska, Magdalena &Zdot;ychowska, Adam Reich Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszów University, Rzeszów, PolandCorrespondence: Magdalena &Zdot;ychowskaDepartment of Dermatology, Institute of Medical Sciences, Medical College of Rzeszów University, Reszów, PolandTel +48 66-942-2237Fax +48 17 86 66 294Email magda.zychowska@gmail.comAbstract: Generalized pustular psoriasis (GPP) is a severe, life-threatening disease that represents a major therapeutic challenge. There is a lack of randomized controlled trials assessing the efficacy of various treatment options for GPP. TNFα inhibitors have proven to be effective and are increasingly used in this indication. In the current paper, we present two patients with GPP treated with infliximab (Ifx) and a literature review appraising currently available data on the use of Ifx in GPP. Case 1 was a 73-year-old woman with GPP who exhibited lack of treatment response or primary intolerance to standard therapeutic options (high-dose acitretin, methotrexate, cyclosporine A, and methylprednisolone). However, Ifx therapy combined with low-dose acitretin resulted in rapid and sustained resolution of skin lesions. Case 2 was a 60-year-old man with GPP and numerous comorbidities who was initially treated with Ifx in combination with methotrexate, with good treatment response for 9 months. Following an infection-induced flare of GPP at week 38, methotrexate was discontinued in favor of low-dose acitretin and Ifx continued. This regimen again resulted in rapid resolution of pustules. We present these cases to highlight the advantage of long-term Ifx therapy with low-dose acitretin in GPP.Keywords: infliximab, anti-TNFα, generalized pustular psoriasis, acitretin

Vaccines are pivotal for control of the coronavirus disease (COVID-19) pandemic. Patients with inflammatory bowel diseases (IBDs) treated with antitumor necrosis factor (TNF)-α have lower serologic response after two COVID-19 vaccine doses. Data regarding a third vaccine dose are scarce. An Israeli multicenter prospective observational study recruited 319 subjects: 220 with IBD (79 treated with anti-TNFα) and 99 healthy control (HC) participants. All patients received two mRNA-BNT162b2 vaccines (Pfizer/BioNTech), 80% of whom received a third vaccine dose. Evaluation included disease activity, anti-spike (S) and nucleocapsid (N) antibody levels, anti-TNFα drug levels, and adverse events (AEs). All participants showed significant serologic response one month after receiving a third dose. However, three months later, the anti-S levels decreased significantly in patients treated with anti-TNFα compared with the non-anti-TNFα and HC groups. A correlation between serologic response to the third vaccine dose and anti-TNF drug levels was not found. No significant AE or IBD exacerbation was observed. Importantly, lower serologic response after the third vaccine dose predicted infection. A third dose of BNT162b2 is effective and safe in patients with IBD. Lower serologic response predicted infection, even in seropositive subjects. Lower serologic responses and their rapid decline suggest a fourth vaccine dose in this patient population.

La artritis psoriásica se acompaña de una serie de comorbilidades cardiovasculares y metabólicas. La obesidad transcribe un estado de inflamación sistémica de bajo grado. Además, es un predictor negativo de la respuesta al tratamiento. Nuestro objetivo es evaluar si existen interacciones entre el estado metabólico, los parámetros inflamatorios y la actividad de la enfermedad. También queremos comprobar si las enfermedades metabólicas o cardiovasculares tienen alguna asociación con la reducción de la carga inflamatoria mediante el tratamiento de la enfermedad. Hemos realizado un estudio descriptivo transversal de 160 pacientes con artritis psoriásica. Se recogieron variables sociodemográficas, clínicas y analíticas. También se registró la presencia de dactilitis y entesitis, el HAQ, DAPSA y si se cumplen o no los criterios MDA. La prueba de chi-cuadrado y la H de Kruskall Wallis se utilizaron para realizar comparaciones, considerando p < 0,05 como estadísticamente significativo. Para establecer correlaciones, se utilizó el coeficiente de correlación de Pearson. El IMC y el perímetro abdominal se correlacionan con la PCR y la VSG (significación < 0,05) aunque la fuerza de correlación es baja (Pearson < 0,4), pero no con DAPSA o con cumplir los criterios de MDA. El uso de terapias biológicas se asocia con una menor prevalencia de eventos cardiovasculares (p = 0,047; OR: 0,12; IC 95%: 0,01-0,9) y de entesitis (p = 0,008; OR: 0,3; IC 95%: 0,16-0,56). También se asocia a unos niveles normales de PCR (p = 0,029; OR: 0,25; IC 95%: 0,07-0,87) y VSG (p = 0,024; OR: 0,36; IC 95%: 0,16-0,82) cuando se compara con las terapias convencionales. El tratamiento anti-TNFα podría reducir el riesgo cardiovascular en pacientes con artritis psoriásica. Puede haber niveles más altos de PCR y VSG en personas obesas sin que esto implique necesariamente una mayor actividad de la enfermedad. Psoriatic arthritis is accompained by several cardiometabolic comorbidities. Obesity causes a low-grade systemic inflammation and is a negative predictor of treatment response. We wanted to evaluate if there are interactions between metabolic status, inflammatory parameters and disease activity; and whether metabolic or cardiovascular diseases have any association with the reduction of the inflammatory burden by treating the psoriatic arthritis. We have carried out a cross-sectional descriptive study of 160 patients with psoriatic arthritis. Sociodemographic, clinical and analytical variables were collected, as well as the presence of dactylitis and enthesitis; and HAQ, DAPSA and Minimal Disease Activity criteria. Chi-square test and the H of Kruskall Wallis were used to carry out comparisons, considering P <.05 as statistically significant. To establish correlations, Pearson correlation coefficient was used. BMI and waist circumference correlate with CRP and ESR (significance: <.05) although the correlation strenght is low (Pearson <.4), but there is no such relationship with DAPSA or meeting MDA criteria. Using biologic therapies is associated with a lower prevalence of cardiovascular events (P = 0.047; OR: 0.12, 95% CI: 0.01-0.9) and enthesitis (P =.008; OR: 0.3, CI 95%: 0.16-0.56); and normal levels of CRP (P =.029; OR: 0.25, 95% CI: 0.07-0.87) and ESR (P = 0.024; OR: 0.36, 95% CI: 0.16-0.82) when comparing to conventional therapies. Anti-TNFα treatment could reduce cardiovascular risk in patients with psoriatic arthritis. There may be higher levels of CRP and ESR in obese individuals without this necessarily implying higher disease activity. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is an idiopathic and chronic disorder that includes ulcerative colitis (UC) and Crohn's disease (CD). Both diseases show an uncontrolled intestinal immune response that generates tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells that play a key role in tolerance maintenance in the gastrointestinal mucosa. Although it has been reported that DC recruitment by the intestinal mucosa is more prominent in IBD patients, the specific mechanisms governing this migration are currently unknown. In this study, the expression of several homing markers and the migratory profile of circulating DC subsets towards intestinal chemo-attractants were evaluated and the effect of biological drugs with different mechanisms of action, such as anti-TNFα or anti-integrin α4β7 (vedolizumab), on this mechanism in healthy controls (HCs) and IBD patients was also assessed. Our results revealed that type 2 conventional DCs (cDC2) express differential homing marker profiles in UC and CD patients compared to HCs. Indeed, integrin β7 was differentially modulated by vedolizumab in CD and UC. Additionally, although CCL2 displayed a chemo-attractant effect over cDC2, while biological therapies did not modulate the expression of the homing markers, we paradoxically found that anti-TNF-treated cDC2 increased their migratory capacity towards CCL2 in HCs and IBD. Our results therefore suggest a key role for cDC2 migration towards the intestinal mucosa in IBD, something that could be explored in order to develop novel diagnostic biomarkers or to unravel new immunomodulatory targets in IBD. [ABSTRACT FROM AUTHOR]

Background: People with inflammatory bowel disease (IBD) including ulcerative colitis are at risk for colorectal cancer. Despite available effective drugs used to treat IBD, many patients fail or lose response over time with some displaying drug-induced adverse events. Saffron (Crocus sativus) has been reported to have anti-inflammatory properties. Its protective role in IBD has not been explored extensively. Aim: To establish whether saffron treatment alleviates inflammation in experimental colitis. Methods: Colitis was induced in C57BL/6 mice with 3% DSS and treated with either saffron doses (7.5, 15, 20, 25 mg/kg body weight) or vehicle through daily gavage. On day 11, mice were euthanized and analyzed for gross and microscopic inflammation. Distal colon segments were collected for mRNA and protein expression of HO-1 protein and GPX2, (the downstream targets of NRF-2). Nrf-2 translocation from cytosol to nucleus was confirmed by immunofluorescence, and further Nrf-2 protein expression in nuclear and cytosolic fraction of colon was analyzed by immunoblot. Immune cells were isolated from the lamina propria of mouse colon for flow cytometry-based immunophenotyping. Colitis was also induced in C57BL/6 Ahr knockout and wild type mice to explore the involvement of Ahr-dependent pathways in saffron's protective effect(s). The therapeutic effect of saffron was further validated in another TNBS model of colitis. Results: Saffron 20 mg/kg body weight showed improved colon gross and histology features and led to better body weight, colon length, histology score, and reduced disease activity index (DAI). Saffron significantly decreased pro-inflammatory macrophages (M1), while increasing anti-inflammatory macrophages (M2) and IL10 + dendritic cells. Saffron treatment also enhanced CD3 + T and CD3 + CD8 + T cells followed by increase in different CD3 + CD4 + T cells subsets like CD25 + T cells, FoxP3 + CD25 + regulatory T cells, and CD4 + FOXP3 + CD25-regulatory T cells. Immunoblot analysis showed a significant increase in HO-1/GPX2 protein expression. With saffron treatment, Nrf-2 translocation into nucleus from cytosol also supports the involvement of Nrf-2 and its downstream targets in the protective effect of saffron. Further, we demonstrated that saffron in part exert anti-inflammatory effect through activation of aryl hydrocarbon receptor (AhR)-nuclear factor erythroid 2–related factor 2 (Nrf2)-dependent pathways. Conclusion: These data demonstrate saffron's therapeutic potential and its protective role in part via Ahr/Nrf-2 pathways and regulatory innate and adaptive immune cells. [ABSTRACT FROM AUTHOR]

Background and Aim: Anti‐tumor necrosis factor (TNF)α antibody (ATA) and biologics/molecular targeted agents with other mechanisms (non‐ATA) are currently available for refractory ulcerative colitis (UC). However, the knowledge about optimal drug selection after the initial treatment with ATA failure is lacking. This study assessed whether the response to the initial ATA could be a basis for selecting subsequent agents in UC patients. Methods: Ulcerative colitis patients treated with ATA or non‐ATA as the subsequent biologic after the failure of initial ATA were retrospectively analyzed. The efficacy at 14 weeks was examined according to the response to initial ATA. Results: Of 163 patients treated with the first ATA, the efficacy of subsequent ATA and non‐ATA was evaluated in 63 and 36, respectively. Remission and response to subsequent‐line therapy, regardless of ATA or non‐ATA, were lower in patients with primary nonresponse (PNR) to initial ATA than in patients with efficacy to initial ATA (33.3% vs 69.2%, P < 0.01). In patients with PNR to initial ATA, the remission rate with subsequent ATA was significantly lower than with subsequent non‐ATA (4.3% vs 26.3%, P = 0.04). In patients who showed efficacy to initial ATA, the remission rate with subsequent ATA was also lower than that with subsequent non‐ATA (30.6% vs 56.3%, P = 0.08). PNR with initial ATA was the predictor of PNR to subsequent ATA (odds ratio: 5.62, 95% confidence interval: 1.50–21.7). Conclusion: Non‐ATA may be suitable in UC patients as the subsequent biologics regardless of the outcome of the first ATA. [ABSTRACT FROM AUTHOR]

Background and aimAnti-TNFα is measurable in infants exposed in utero up to 12 months of age. Data about the exposure effect on the infant’s adaptive immunity are limited. We aimed to prospectively evaluate the distribution and function of T and B cells, in infants of females with inflammatory bowel disease, in utero exposed to anti-TNFα or azathioprine.MethodsA prospective multi-center study conducted 2014–2017. Anti-TNFα levels were measured in cord blood, and at 3 and 12 months. T-cell repertoire and function were analyzed at 3 and 12 months by flow-cytometry, expression of diverse T cell receptors (TCR) and T-cell receptor excision circles (TREC) quantification assay. Serum immunoglobulins and antibodies for inactivated vaccines were measured at 12 months. Baseline clinical data were retrieved, and 2-monthly telephonic interviews were performed regarding child infections and growth.Results24 pregnant females, age 30.6 (IQR 26.5–34.5) years were recruited, 20 with anti-TNFα (infliximab 8, adalimumab 12), and 4 with azathioprine treatment. Cord blood anti-TNFα was higher than maternal blood levels [4.3 (IQR 2.3–9.2) vs. 2.5 (IQR 1.3–9.7) mcg/ml], declining at 3 and 12 months. All infants had normal number of B-cells (n = 17), adequate levels of immunoglobulins (n = 14), and protecting antibody levels to Tetanus, Diphtheria, Hemophilus influenza-B and hepatitis B (n = 17). All had normal CD4+, CD8+ T-cells, and TREC numbers. TCR repertoire was polyclonal in 18/20 and slightly skewed in 2/20 infants. No serious infections requiring hospitalization were recorded.ConclusionWe found that T-cell and B-cell immunity is fully mature and immune function is normal in infants exposed in utero to anti-TNFα, as in those exposed to azathioprine. Untreated controls and large-scale studies are needed to confirm these results.

While anti-TNFα has been established as an effective therapeutic approach for several autoimmune diseases, results from clinical trials have uncovered heterogeneous patients' response to therapy. Here, we conducted a meta-analysis on the publicly available gene expression cDNA microarray datasets that examine the differential expression observed in response to anti-TNFα therapy with psoriasis (PsO), inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Five disease-specific meta-analyses and a single combined random-effects meta-analysis were performed through the restricted maximum likelihood method. Gene Ontology and Reactome Pathways enrichment analyses were conducted, while interactions between differentially expressed genes (DEGs) were determined with the STRING database. Four IBD, three PsO and two RA datasets were identified and included in our analyses through our search criteria. Disease-specific meta-analyses detected distinct pro-inflammatory down-regulated DEGs for each disease, while pathway analyses identified common inflammatory patterns involved in the pathogenesis of each disease. Combined meta-analyses further revealed DEGs that participate in anti-inflammatory pathways, namely IL-10 signaling. Our analyses provide the framework for a transcriptomic approach in response to anti-TNFα therapy in the above diseases. Elucidation of the complex interactions involved in such multifactorial phenotypes could identify key molecular targets implicated in the pathogenesis of IBD, PsO and RA. [ABSTRACT FROM AUTHOR]

La sarcoïdose est une maladie systémique granulomateuse, caractérisée par une atteinte médiastinopulmonaire, chez la majorité des patients et, plus rarement, par des atteintes extrapulmonaires, comme des atteintes oculaires, cutanées, des glandes exocrines, ganglionnaires et articulaires. Les atteintes neurologiques et cardiaques sont plus rares, mais font toute la gravité de la maladie. Les atteintes cardiaques concernent 5 à 20 % des patients, selon les séries, et touchent même plus de 25 % des patients dans les séries autopsiques. Cette revue vise à faire le point sur l'intérêt diagnostique des différentes techniques d'imagerie dans la sarcoïdose cardiaque et également détailler la prise en charge « interniste » et cardiologique de ces patients qui requièrent une prise en charge pluridisciplinaire. Sarcoidosis is a systemic granulomatous disease characterized by pulmonary involvement in most patients and more rarely by extrapulmonary involvement such as ocular, skin, salivary, lymph nodes and joints damages. Neurological and cardiac involvements are uncommon but are associated with increased morbidity and mortality. Cardiac sarcoidosis affects 5 to 20% of patients depending on the studies and autopsy studies even report cardiac involvement in 25% of sarcoidosis patients. This review aims to summarise main data on the diagnostic value of the different imaging techniques in cardiac sarcoidosis and to also detail the management of these patients who require a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate effectiveness and safety of infliximab dose escalation in Takayasu arteritis (TAK) patients. To identify factors associated with refractoriness to standard-dose infliximab. Methods: Medical records of infliximab-treated TAK patients from a large single-centre observational cohort were reviewed. Infliximab therapy duration, concomitant therapies, and reasons for dose escalation and therapy suspension were evaluated. Occurrence of adverse events was recorded. A comparison between patients who maintained infliximab standard-dose and those who needed dose-escalation was performed. Factors associated with refractoriness to standard dose were analysed. Results: Forty-one patients were included. Starting infliximab dose was 5mg/kg 6-weekly and 28 patients (68%) needed dose escalation. Persistence/recurrence of clinical symptoms was the most frequent reason for escalation. Median therapy duration was 39 (IQR, 26-61) months in the standard-dose group and 68 (38-87) months in the intensified-dose group. In the intensified-dose-group, infliximab was suspended in eight patients (29%) after a median of 38 (31-71) months, due to loss of response (n = 7) or patient's request (n = 1). Patients in the intensified-dose group had a higher number of relapses (3.4 vs 0.8 events/patient) and received a higher cumulative steroid dose (1.7 [1.6-2.3] vs 1.3 [1-1.6] g/month of prednisone). Three patients from the intensified-dose group had serious infections; one patient from the standard-dose group developed paradoxical psoriasis. At univariate analysis, age at diagnosis and age at infliximab start were associated with infliximab escalation. Conclusion: In TAK, dose escalation is safe and allows to optimise infliximab durability in refractory patients. Younger patients seem to be more refractory to standard dosages. [ABSTRACT FROM AUTHOR]

Introduction Anti-tumor necrosis factor alpha (TNFα) therapies have revolutionized the management of Crohn's disease (CD). However, they increase the risk of viral reactivation, particularly hepatitis B virus (HBV). This study aims to define the HBV serological profiles of patients with CD who are candidates for biological therapy, identifying profiles at potential risk for reactivation or exacerbation following immunosuppressive treatment. Materials and methods This descriptive retrospective study included patients with CD, aged over 16 years, who were candidates for anti-TNFα treatment at Ibn Sina University Hospital Center (UHC) in Rabat, Morocco, from January 2015 to March 2023. The serological profiles of patients, including hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies, and total hepatitis B core antibodies (HBcAb), were determined using microparticle chemiluminescence immunoassay with the ARCHITECT i2000sr or Alinity (Abbott Diagnostics, Chicago, Illinois, United States) automated systems at the Central Virology Laboratory (CVL) of Ibn Sina UHC Rabat. HBV DNA quantification was performed using the m2000 Abbott Diagnostic or GeneXpert system. Results Out of 249 patients with CD who were candidates for biological therapy, 131 (52.6%) received anti-TNFα treatment, including 39 (29.8%) with adalimumab and 92 (70.2%) with infliximab. The median age was 41 years, and the male-to-female ratio was 0.52. The overall HBV screening rate before starting biological therapy was 68.7%. HBV screening was conducted for 90 patients at the CVL, where serological marker analysis categorized five distinct profiles. A majority of patients (65, 72.2%) had negative serological profiles for HBV, while 10 (11.1%) were immunized via vaccination. Profiles at risk of viral reactivation or worsening following immunosuppressive therapy included 12 (13.3%) patients immunized by contact, two (2.3%) with isolated HBcAb, and one (1.1%) with active viral hepatitis (positive HBsAg and HBcAb), who was initiated on tenofovir 300 mg before starting combination therapy. No cases of primary infection or viral B reactivation were observed during the study. Conclusions In our study, 15 patients (16.7%) exhibited a potential risk of viral reactivation or worsening of HBV following the initiation of immunosuppressive therapy. The authors recommend precise patient selection, thorough pretreatment evaluation, and regular follow-up during therapy to minimize adverse events associated with anti-TNFα treatment. Additionally, a prophylactic or preemptive strategy should be considered. The risk of late reactivation after discontinuation of biological therapy should also be carefully monitored., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Louhab et al.)

• In GPA, relapses remain frequent and refractory manifestations may occur. • Off-label use of TNF-α blockers shows efficacy in less than 50% of refractory and/or relapsing GPA. • Off-label use of abatacept shows efficacy in less than 50% of refractory and/or relapsing GPA. To describe the efficacy and safety of off-label use of biologics for refractory and/or relapsing granulomatosis with polyangiitis (GPA). We conducted a French retrospective study including GPA patients who received off-label biologics for refractory and/or relapsing disease after failure of conventional immunosuppressive regimens. Among 26 patients included, 18 received infliximab (IFX), 2 adalimumab (ADA) and 6 abatacept (ABA). Biologics were initiated in median as 4th-line therapy (IQR 3–6) for relapsing and/or refractory disease in 23 (88%) and/or significant glucocorticoid-dependency in 8 cases (31%). At biologics initiation, median (IQR) BVAS and prednisone dose in anti- TNF-α and ABA recipients were 7 (3–8) and 2 (1–6), and 20 (13–30) mg/day and 20 (15–25) mg/day, respectively. Clinical manifestations requiring biologics were mainly pulmonary and ENT manifestations in 58% each. Anti-TNF-α and ABA were continued for a median duration of 8 months (IQR 6–13) and 11 months (IQR 6–18) respectively. Anti-TNF-α recipients showed remission, partial response and treatment failure in 10%, 30% and 60% at 6 months, and 25%, 20% and 55% at 12 months, respectively. ABA recipients showed remission, partial response and treatment failure in 17%, 33% and 50% at 6 months and 17%, 33% and 50% at 12 months. One patient treated with IFX experienced life-threatening reaction while one patient treated with ABA experienced a severe infection. This real-life study suggests that off-label use of anti-TNF-α and abatacept shows efficacy in less than 50% of refractory and/or relapsing GPA. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel diseases (IBD) are often treated with anti-tumor necrosis factor alpha (anti-TNFα) medications. Concomitant treatment of IBD with anti-TNFα agents and immunomodulators appears to be associated with an increased risk for lymphoma. Methods: Patients who developed lymphoma while on monotherapy with an anti-TNFα agent were identified at three centers. Institutional Review Board approval was obtained. Results: Five adolescents and young adult patients with pediatric-onset IBD who were treated with infliximab (IFX) without exposure to thiopurines were subsequently diagnosed with lymphoma. Three of the five patients had bone involvement at presentation. Epstein–Barr virus was positive in 2 cases. Median time from diagnosis of IBD and exposure to IFX prior to diagnosis of lymphoma was 5 and 4.3 years, respectively. Conclusions: This case series reports long-term follow-up for young patients with IBD who were treated with IFX monotherapy and developed lymphoma. Three of the five patients had bone involvement. In general, the risk of lymphoma following exposure to anti-TNFα medications alone remains low, but the incidence of primary bone lymphomas in IBD has not been reported. Studies examining longer exposure times may be needed to determine the true lymphoma risk in patients treated with IFX monotherapy. [ABSTRACT FROM AUTHOR]

Anti-TNFα represent one of the main treatment approaches for the management of inflammatory bowel diseases (IBD). Therefore,the evaluation of their treatment patterns over time provides valuable insights about the clinical value of therapies and associated costs. To assess the treatment patterns with the first anti-TNFα in IBD. Retrospective, observational study. 310 IBD patients were analyzed along a 5-year follow-up period. 56.2% of Crohn's disease (CD) patients started with adalimumab (ADA), while 43.8% started with infliximab (IFX). 12.9% of ulcerative colitis (UC) patients initiated with ADA, while 87.1% initiated with IFX. Treatment intensification was required in 28.9% of CD and 37.1% of UC patients. Median time to treatment intensification was shorter in UC than in CD (5.3 vs. 14.3 months; p = 0.028). Treatment discontinuation due to reasons other than remission were observed in 40.7% of CD and 40.5% of UC patients, although, in UC patients there was a trend to lower discontinuation rates with IFX (36.6%) than with ADA (66.7%). Loss of response accounted for approximately one-third of discontinuations, in both CD and UC. Around one-third of IBD biologic-naive patients treated with an anti-TNFα required treatment intensification (earlier in UC) and around 40% discontinued the anti-TNFα due to inappropriate disease control. [ABSTRACT FROM AUTHOR]

Background: ABP501 is a biosimilar to Reference Adalimumab (HUMIRA®) produced by AMGEN. Adalimumab (ADA) has a marketing authorization for Crohn's disease, ulcerative colitis and other inflammatory or autoimmune diseases. The aim of this study was to evaluate the LISA-TRACKER assays developed by Theradiag (France), for the monitoring of ABP501 and anti-ABP501 antibodies in human serum. Results: 68 ABP501 clinical samples were measured with the LISA TRACKER Duo Adalimumab assay. LISA TRACKER has been validated as suitable for quantification of ABP501 in human serum samples. Accuracy of the LISA-TRACKER was measured using 3 human serum matrices spiked with known levels of biosimilar, 3 levels spanning the dynamic range. Percentages of recovery were ranged from 90 to 120% for biosimilar batch1, and between 93 and 105% for biosimilar batch2. The acceptance criteria (CV < 20%) were met for intra-run (from 3.8 to 16.5%) and inter-run imprecision (from 4.4 to 13.9%) including the two batches. All results were comprised within ± 20% from results, obtained with the kit and sample unexposed in order to evaluate stability of the sample, stability of the kit and consistency of the results. In any case, but two, all percentages of inhibition were > 50% for specificity. Specificity was tested with Biosimilar spiked samples, Biosimilar with Humira® spiked samples, and clinical samples from patients treated with adalimumab biosimilar. All of these samples were spiked with polyclonal antibodies directed against Humira®. Specificity inhibition and specificity detection steps were also part of the validation parameters. Reagents made with ABP501 gave similar results than reagents made with Humira® meeting acceptance criteria. Conclusions: LISA-TRACKER ADA and anti-ADA assays are reliable for the monitoring of patients treated with ABP501. [ABSTRACT FROM AUTHOR]

Abstract Background Anti-Tumor Necrosis Factor-alpha therapy has become clinically important for treating inflammatory bowel disease. However, the use of conventional immunotherapy requires a systemic exposure of patients and collateral side effects. Lactic acid bacteria have been shown to be effective as mucosal delivering system for cytokine and single domain antibodies, and it is amenable to clinical purposes. Therefore, lactic acid bacteria may function as vehicles for delivery of therapeutic antibodies molecules to the gastrointestinal tract restricting the pharmacological effect towards the gut. Here, we use the mucosal delivery of Lactococcus lactis carrying an anti-TNFα scFv expression plasmid on a DSS-induced colitis model in mice. Results Experimental colitis was induced with DSS administered in drinking water. L. lactis carrying the scFv expression vector was introduced by gavage. After four days of treatment, animals showed a significant improvement in histological score and disease activity index compared to those of untreated animals. Moreover, treated mice display IL-6, IL17A, IL1β, IL10 and FOXP3 mRNA levels similar to health control mice. Therefore, morphological and molecular markers suggest amelioration of the experimentally induced colitis. Conclusion These results provide evidence for the use of this alternative system for delivering therapeutic biopharmaceuticals in loco for treating inflammatory bowel disease, paving the way for a novel low-cost and site-specific biotechnological route for the treatment of inflammatory disorders.

Background: Patients living with HIV (PLWHIV) can develop autoimmune diseases (AD) needing immunosuppressive treatments (IST). This study aims to describe the impact of IST in PLWHIV. Methods: This was a multicentric retrospective observational study in six HIV referral centers on PLWHIV under IST for AD. Demographic factors, viral co-infections, immunovirological status before and under IST, infectious events, and their descriptions were collected and described focusing on infectious events, immunovirological variations, and IST effectiveness. Results: 9480 PLWHIV were screened for inclusion. Among them, 138 (1.5%) had a history of auto-immune disease, among which 32 (23%) received IST. There was mainly spondyloarthropathy (28%) and the most commonly used IST was methotrexate. The median follow-up under IST was 3.8 years (2.7; 5.9). There were 15 infectious events (0.5 events/individuals) concerning nine patients. At the last medical follow-up, 81% of these were in remission of their AD. Under IST, there was an increase in CD4 during follow-up (629 vs. 827 CD4/mm3, p = 0.04). No HIV virological failure was noted. Conclusions: This study supports a growing evidence base that IST can be used safely and effectively in PLWHIV with careful monitoring.

The efficacy of the COVID-19 mRNA vaccine, including the third vaccination in pediatric inflammatory bowel disease (PIBD) patients is not fully understood. This study aimed to evaluate the humoral immunogenicity of the BNT162b2 vaccine and the changes in durability until 20–28 weeks after the initial vaccine series in PIBD patients on immunosuppressive drugs. The safety of the initial vaccine series and the booster effect of the third vaccination were also evaluated. A single-center, prospective cohort study was conducted, and 63 participants (anti-TNFα: 11; non-anti-TNFα: 31; 5-ASA: 21), with a mean age of 15.2 (range 9.6–17.9) years, were enrolled. All PIBD patients were seroconverted, with no serious short-term AEs. PIBD patients on anti-TNFα had significantly lower antibody titers than those on other medications at all measurement points. Furthermore, antibody titers waned over time with anti-TNFα and were significantly lower at 20–28 weeks than at 3–9 weeks after a two-vaccine series. In all 10 patients (anti-TNFα: 5; non-anti-TNFα including 5-ASA: 5), the third vaccination led to antibody concentrations significantly higher than those at the same time point after the second vaccination. PIBD patients on anti-TNFα need to remain vigilant about COVID-19 even after two vaccinations, and a third vaccination may be considered.

Inflammatory bowel disease (IBD) is an idiopathic and chronic disorder that includes ulcerative colitis (UC) and Crohn’s disease (CD). Both diseases show an uncontrolled intestinal immune response that generates tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells that play a key role in tolerance maintenance in the gastrointestinal mucosa. Although it has been reported that DC recruitment by the intestinal mucosa is more prominent in IBD patients, the specific mechanisms governing this migration are currently unknown. In this study, the expression of several homing markers and the migratory profile of circulating DC subsets towards intestinal chemo-attractants were evaluated and the effect of biological drugs with different mechanisms of action, such as anti-TNFα or anti-integrin α4β7 (vedolizumab), on this mechanism in healthy controls (HCs) and IBD patients was also assessed. Our results revealed that type 2 conventional DCs (cDC2) express differential homing marker profiles in UC and CD patients compared to HCs. Indeed, integrin β7 was differentially modulated by vedolizumab in CD and UC. Additionally, although CCL2 displayed a chemo-attractant effect over cDC2, while biological therapies did not modulate the expression of the homing markers, we paradoxically found that anti-TNF-treated cDC2 increased their migratory capacity towards CCL2 in HCs and IBD. Our results therefore suggest a key role for cDC2 migration towards the intestinal mucosa in IBD, something that could be explored in order to develop novel diagnostic biomarkers or to unravel new immunomodulatory targets in IBD.

Background and Aims: Angiotensin-converting enzyme II (ACE2) is the key molecule for understanding the pathophysiology of COVID-19. The risk of COVID-19 and impact of immunosuppressive treatment on disease course in patients with inflammatory bowel disease (IBD) remain controversial. We aimed to determine the change of intestinal ACE2 expression before and after biologics treatment including anti-tumor necrosis factor α (anti-TNFα), anti-integrin, and anti-interleukin (IL)12/23 in IBD patients.Methods: We analyzed the ACE2 expression through the public database of paired intestinal biopsies from IBD patients before and after biologic therapy. Change of ACE2 RNA and protein expression were validated in two independent cohorts (Birmingham cohort and Guangzhou cohort). The correlation between ACE2 expression and disease activity was also analyzed.Results: Mining information from the GEO database showed that compared with healthy control, intestinal ACE2 expression was downregulated in ileum of CD patients, while upregulated in colon of both CD and UC patients. Colonic ACE2 RNA expression was decreased significantly in patients responding to anti-TNFα but not anti-integrin and anti-IL12/23, which was validated in the Birmingham cohort. Using the Guangzhou cohort including 53 patients matched by pre- and post-anti-TNFα therapy, colonic ACE2 protein expression was significantly downregulated after anti-TNFα treatment in responders (P < 0.001) rather than non-responders. Colonic ACE2 expression was significantly higher in patients with severe histologically active disease compared with those with moderate (P < 0.0001) and mild (P = 0.0002) histologically active disease.Conclusion: Intestinal inflammation influences the expression of intestinal ACE2 in IBD patients, with different alterations in the ileum and colon. Colonic ACE2 expression was downregulated after anti-TNFα therapy in IBD patients responding to treatment. This might provide new clues regarding the risk of SARS-CoV-2 infection and the potential benefit of sustaining anti-TNFα treatment in patients with IBD.

Literature regarding the effect of biologics on the course of mycosis fungoides (MF) is scarce. This multicentre study analysed retrospective data on 19 patients with MF, who were treated with biologics; 12 for inflammatory conditions coexisting with MF, and 7 for MF misdiagnosed as an inflammatory skin disease. Eight patients were treated with anti-tumour necrosis factor-α-monotherapy; 6 had early-stage MF, in 3 patients MF preceded and in 3 MF was diagnosed after initiation of biologics, with no stage-progression or with stable disease, respectively (median treatment time concurrent with MF 57 months). Two patients had advanced stage MF: IIB, treated for 15 months with no stage-progression, and IVA1, treated for 8 months, died of disease 10 months later. The other 11/19 patients received anti-interleukin-17A and/or anti-interleukin-12/23 or anti-interleukin-23 (with/without anti-tumour necrosis factor-α/anti-interleukin-4/13), with stage-progression in 8 patients after a median of 8 months’ treatment. Although, in general, biologics should be avoided in patients with MF, these results indicate that anti-tumour necrosis factor-α-monotherapy might not aggravate the disease course in early-stage patients. Interleukin-17A, interleukin-12/23 and interleukin-23 pathway-blockers may prompt progression of MF.

Artemis Matsou,1 Konstantinos T Tsaousis2 1Second Department of Ophthalmology, Papageorgiou General Hospital, Aristotle University of Thessaloniki, Greece; 2Ophthalmology Department, Leicester Royal Infirmary, University Hospitals of Leicester, Leicester, UK Background: Sarcoidosis constitutes one of the leading causes of ocular inflammation. Chronic ocular sarcoidosis can affect any segment of the eye and its adnexa, producing a wide range of clinical manifestations and severity. If left untreated, permanent visual impairment or even blindness may ensue. Treatment approaches vary from topical therapy to systemic agents that induce immunosuppression to different levels according to disease severity. Objective: To review the published literature on the management options for chronic ocular sarcoidosis and provide a comprehensive list of available treatment strategies, including the newer biologics. Summary: Ocular disease remains a challenging aspect of sarcoidosis and may even be the presenting sign of the disease. Prompt and effective therapy may reverse visual damage and prevent permanent loss of vision. Because of the complexity of the disease, a multidisciplinary approach is often required, with a view to addressing both the ocular and other systemic manifestations of sarcoidosis. Recent data suggest that achieving overall optimal systemic control is of paramount importance in controlling eye inflammation as well. Cytotoxic immunosuppressive agents for refractory chronic ocular disease, as well as biologic anti-TNFα therapies, have advanced the management of chronic disease and should be considered corticosteroid-sparing strategies before the onset of significant steroid-induced morbidity. Keywords: ocular sarcoidosis, uveitis, immunosuppression, biologic agents, anti-TNFα

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Objective To summarize evidence regarding efficacy of anti-TNFα in childhood chronic uveitis, refractory to common DMARDs. Methods An updated systematic search was conducted between November 2012 and January 2020. Studies investigating the efficacy of anti-TNFα therapy, in children of ages <16 years, as the first biologic treatment for childhood chronic uveitis, refractory to topical and/or systemic steroid and at least one DMARD were eligible for inclusion. The primary outcome measure was the improvement of intraocular inflammation according to Standardization of Uveitis Nomenclature Working Group criteria. A combined estimate of the proportion of children responding to etanercept (ETA), infliximab (INF), and adalimumab (ADA) was determined. Results We identified 1677 articles of which 37 articles were eligible. Three were randomized controlled trials, one on ETA and two on ADA, and were excluded from pooled analysis. From the observational studies, a total of 487 children were identified: 226 received ADA, 213 INF and 48 ETA. The proportion of responding children was 86% (95% CI: 76%, 95%) for ADA, 68% (95% CI: 50%, 85%) for INF and 36% (95% CI: 9%, 67%) for ETA. Pooled analysis showed clear differences (χ2 = 32.2, P  < 0.0001): ADA and INF were both significantly superior to ETA (χ2 = 26.8, P  < 0.0001, and χ2 = 7.41, P  < 0.006, respectively), ADA significantly superior to INF (χ2 = 13.4, P  < 0.0002). Conclusion This meta-analysis, consistent with recent randomized controlled trial data, suggests the efficacy of ADA and INF in childhood chronic uveitis treatment. However, ADA results were superior to those of INF in this clinical setting. [ABSTRACT FROM AUTHOR]

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Antagonists of tumour necrosis factor α (TNFα) are a common therapeutic choice for autoimmune diseases. Although they are effective and relatively safe, an increasing number of immune-mediated adverse events have been reported. Among these, neurological adverse effectsm such as consisting of demyelinating events in the central and peripheral nervous system were described. Demyelination of the central nervous system is a rare complication after treatment with TNFα antagonists. Here, we report a case of multiple sclerosis under treatment with TNFα antagonists and discuss its etiopathogenesis. This 45-year-old female patient developed signs and symptoms suggestive of primary progressive multiple sclerosis during treatment with adalinumab for nodular cystic acne, and magnetic resonance imaging of the patient showed typical lesions of demyelinating disease. [ABSTRACT FROM AUTHOR]