anti-IL-6 Research Articles

Treatment of psoriasis with biologic and non-biologic targeted therapies in patients with latent tuberculosis infection or at risk for tuberculosis disease progression: Recommendations from a SPIN-FRT expert consensus.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non-contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune-mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti-TNF therapy. These recommendations have extended to IL-12/23, IL-17, IL-23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real-world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL-17 and IL-23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN-FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non-biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management.

Head-to-head studies on psoriasis and psoriatic arthritis

Given the ever-increasing number of approved therapies for the treatment of psoriasis (PsO) and psoriatic arthritis (PsA), head-to-head (H2H) comparative studies are essential. These are aimed primarily at acomparative analysis of treatment effectiveness. In both PsO and PsA, biological disease-modifying antirheumatic drugs (bDMARD) have been shown to be superior to conventional therapies in H2H studies. In PsO interleukin 17 (IL-17) and IL-23 inhibitors proved superiority compared to tumor necrosis factor (TNF) inhibitors (etanercept and adalimumab) in several studies. Ustekinumab was more effective than etanercept, but less effective than IL-17 and IL-23 inhibitors. Only afew H2H studies have been published on the treatment of PsA. In the Spirit H2H study ixekizumab was superior to adalimumab using acombined endpoint of arthritis and psoriasis response (ACR-50 and PASI-100). When looking at arthritic symptoms only (ACR-20), secukinumab was not significantly superior to adalimumab in the EXCEED study but was superior in terms of the effect on skin involvement (PASI90). Other H2H studies focused on the treatment of enthesitis (ECLIPSA study), the efficacy of Janus kinase (JAK) inhibition (SELECT-PSA-1) or the additional administration of methotrexate to bDMARD treatment (MUST study). The H2H data have been incorporated into the treatment guidelines and have led to IL-17 and IL-23 inhibition being preferred over TNF inhibition in cases of relevant skin involvement in PsA.

Successful treatment of PD1-inhibitor induced psoriasiform dermatitis using IL-17 blockade without compromising immunotherapy efficacy.

Pembrolizumab is a monoclonal PD-1 inhibitor used in the treatment of lung cancer in addition to several other malignancies. Psoriasiform dermatitis is a well-documented adverse effect. We present a 68 year-old-male with a 50-year smoking history and a 30-year remote history of plaque psoriasis, limited to the knees and elbows, who presented with metastatic non-small cell lung cancer. He was started on a chemotherapy regimen of carboplatin, paclitaxel, and pembrolizumab. One month later, he presented to dermatology with diffuse erythematous scaly papules coalescing into plaques on 80% of body surface area (BSA). Pembrolizumab treatment was paused. The patient was prescribed triamcinolone 0.1% twice daily, but still had significant BSA at one-month and was started on an Il-17 inhibitor, ixekizumab, clearing the psoriasiform dermatitis. He was rechallenged with pembrolizumab every 3 weeks and repeat PET/CT demonstrated excellent tumor response. This case prompted a literature review to further characterize the use of IL-17 inhibitors for psoriasiform dermatitis in the setting of ICI therapy. All six cases demonstrated improvement of psoriasiform dermatitis, with two cases showing partial response and four cases showing complete resolution. In three of the six cases, the patients exhibited clinical response to the primary malignancy after rechallenging with ICI, while remaining on an IL-17 inhibitor. Our case, in conjunction with the other reported cases, seems to suggest that IL-17 blockade can maintain a fine balance in this challenging clinical scenario by treating psoriasiform dermatitis without compromising the efficacy of immunotherapy.

Real-World Drug Survival of Biologics and Targeted Synthetic Disease-Modifying Anti-rheumatic Drugs Among Patients with Psoriatic Arthritis.

While the variety of biologics (b) and targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs) available for patients with psoriatic arthritis (PsA) has proved to be efficacious in randomized clinical trials, there is a growing importance to understand the benefits and potential drawbacks of these different therapies in real-world settings, which includes bio-experienced and older patients as well. To evaluate the real-world adherence, drug survival, and discontinuation risk of bDMARDs and tsDMARDs among patients with PsA, comprising both younger and older patients. A retrospective studyusing a computerized database. Treatment-naïve and treatment-experiencedpatients with PsA, younger and older than 60 years, who initiated treatment with bDMARDs [TNF-α inhibitors (TNF-αis), IL-17 inhibitors (IL-17is), IL-12/23 inhibitors (IL-12/23i)] or tsDMARDs (the PDE-4 inhibitor apremilast) during 2015-2018 were included. Adherence was assessed using the proportion of days covered (PDC) method. Time to discontinuation was analyzed using Kaplan-Meier estimates. Risk of discontinuation was estimated by Cox proportional hazard model. We identified 427 eligible patients (22.2 % were older than 60 years), utilizing 673 treatment lines. The proportion of adherent patients (PDC ≥0.8) was similar (62.1-66.5%) across all lines of therapy and across different biologics (70.0-72.0%), while apremilast showed the lowest, in both treatment-naïve and experienced settings (43.6% and 25.5%, respectively). The Kaplan-Meier analysis showed that in the treatment-naïve TNF-αis had higher drug survival compared with apremilast (P = 0.032). Apremilast also had the lowest drug survival in the treatment-experienced group (P < 0.0001). Kaplan-Meier analysis by age groups showed similar drug survival rates in older (≥ 60 years) and younger (age < 60 years) patients, regardless of treatment-experience status. The multivariable model showed that apremilast had increased risk for discontinuation compared with TNF-αis. Adherence, drug survival and risk for discontinuation were similar for all included bDMARDs, regardless of treatment experience status, while apremilast showed lower rates and increased risk. Adherence and discontinuation rate were similar in older and younger patients. With the variety of drug modes of action available for patients with PsA, these findings may assist caregivers in selecting the appropriate treatment.

The utility of IL-23 intraclass switching in the treatment of plaque psoriasis: a retrospective review of 43 cases.

IL-23 inhibitors are a class of injectable biologics consisting of risankizumab, tildrakizumab, and guselkumab utilized for treatment of moderate-to-severe psoriasis. This retrospective review sought to determine the value of IL-23 inhibitor intraclass switching among psoriasis patients after experiencing loss of efficacy to any IL-23 inhibitor. We conducted a retrospective chart review, including 43 patients who underwent any of six potential iterations of IL-23 intraclass switch between 11/2017-11/2023. Most commonly, patients switched from guselkumab or tildrakizumab to risankizumab (83.7%). Patients failed 2.3 ± 1.3 biologic treatments prior to switch. Post-switching, 81.4% of patients achieved BSA <1% after 248.8 ± 126.5 days. BSA immediately prior to intraclass switch was 13.1 ± 8.9 [95% CI: 10.4, 15.8] and at most recent follow-up was 2.9 ± 5.2 [2.3, 5.5]. This research adds to a growing body of literature demonstrating the potential of IL-23 intraclass switching in treatment of moderate-to-severe plaque psoriasis.

Effect of genetically engineered drugs in aseptic necrosis of the femoral head in rats

Bone tissue is a dynamic structure with a metabolic function. The maintenance of bone homeostasis is carried out due to the continuous process of its renewal, remodeling. At the same time, a number of pathological processes, such as ischemic catastrophe, can lead to a violation of the balance of maintaining the constancy of the bone structure. One of these diseases is aseptic necrosis of the femoral head. The presented study analyzes the dynamics of expression of genes involved in maintaining bone tissue homeostasis, changes in the histological picture during the development of aseptic necrosis of the femoral head in laboratory rats that did not receive genetically engineered drugs and against the background of the use of inhibitors of biological action IL-6, TNF-α. After induction of aseptic necrosis in the proximal epiphysis of the femur, the histological picture in animals of different groups was not the same. More preserved bone architectonics and a larger volume of bone plates were recorded in rats receiving genetically engineered drugs compared to animals without the introduction of biological agents. The latter also had the most vivid picture of osteodestruction with increased expression of proinflammatory cytokine genes. In animals, against the background of the use of drugs of inhibitors of the biological action of IL-6, TNF-α, from the second week after induction of aseptic necrosis of the mRNA, the profile of the spongiose bone of the proximal epiphysis of the femur tended to increase the expression of osteoreparation genes. At the same time, the greatest inhibition of osteoclastogenesis gene expression was obtained in rats after injection of a monoclonal antibody to the IL-6 receptor.

Risk of developing inflammatory arthritis in patients with psoriasis initiating treatment with biologics: A population-based analysis

BackgroundThe relationship between biologic treatments for psoriasis (PsO) and development of inflammatory arthritis in patients is not fully understood. ObjectiveAnalyze the effects of biologic treatment on development of inflammatory arthritis in PsO patients. MethodsThis retrospective study assessed PsO patients identified in the Optum Clinformatics® Data Mart database from Jan 2007 to Mar 2023 with no baseline diagnosis of inflammatory arthritis. Patients were stratified based on the class of initial biologic treatment (IL-23, IL-12/23, IL-17, or TNF inhibitor) and followed for up to 3 years or development of inflammatory arthritis. Risk of developing inflammatory arthritis was assessed using a multivariate Cox proportional hazard models using IL-23 inhibitors as reference. ResultsIncidence rates of developing inflammatory arthritis expressed as events/100 person-years were 4.99, 7.29, 6.06, and 9.39 for IL-23, IL-17, IL-12/23, and TNF inhibitors respectively. Adjusted hazard ratios were significantly higher for patients receiving IL-17 (1.44; p=.0294) and TNF (1.90; p<.0001) inhibitors when compared to patients receiving IL-23 inhibitors. LimitationsLimitations include those associated with medical coding errors and the potential for protopathic bias. ConclusionPatients receiving IL-23 inhibitors are at lower risk for developing inflammatory arthritis or PsA compared to those receiving IL-17 and TNF inhibitors.

IL-6 and TIMP-1 Correlated to Airway Pathogen Colonization and Predict Disease Severity in Patients with Non-Cystic Fibrosis Bronchiectasis.

Non-cystic fibrosis bronchiectasis is associated with airway pathogen colonization. We planned to investigate the inflammatory markers in patients with different airway pathogens and their correlation with disease severity. We enrolled patients aged between 20 and 75 from October 2021 to August 2022. All patients had sputum evaluation for bacterial and fungal cultures before enrollment, and were classified into four groups according to the culture results. Forty-four patients with non-CF bronchiectasis and six controls were enrolled and categorized as follows: Group 1, no pathogens identified in sputum cultures (n = 14); Group 2, positive fungal culture results (n = 18); Group 3, positive P. aeruginosa culture results (n = 7); and Group 4, positive culture results for both fungi and P. aeruginosa (n = 5). Group 4 had significantly higher serum defensin α1, IL-6 and tissue inhibitors of MMP (TIMP)-1 levels than group 1 patients. The serum levels of IL-6 and TIMP-1 were positively correlated with the FACED score and negatively correlated with distance-saturation product. Significantly higher levels of serum IL-6 and TIMP-1 were found in the patients who had concomitant fungal and P. aeruginosa colonization, and were closely related to clinical severity and may have important roles in disease monitoring.

Anti-inflammatory potential of low-molecular-weight and high-sulfation-degree sulfated polysaccharides extracted from Antrodia cinnamomea

Two novel sulfated polysaccharides (SPs), N10 and K5 were isolated from ammonium sulfate or potassium sulfate at concentrations of 10 mM and 5 mM in liquid cultures of Antrodia cinnamomea, respectively. N10 and K5 were galactoglucans with a galactose:glucose molar ratio of approximately 1:3. In lipopolysaccharide (LPS)-stimulated RAW264.7 cells, N10 and K5 exhibited strong anti-inflammatory potential, of 56 % and 23 % maximal inhibition of IL-6 and TNF-α production, respectively. Mechanical analysis revealed differences between N10 and K5, with N10 inhibiting the LPS-stimulated phosphorylation of ERK and p38 in RAW264.7 cells. K5 inhibited the LPS-stimulated phosphorylation of AKT and TGFβR-II. N10 and K5 were fragmented into F1, F2, and F3, the molecular weights of which were 455, 24, 0.9, and 327, 36, 1.9 kDa, respectively. K5 F2 and K5 F3 exhibited high degrees of sulfation of 1:3 and 1:8, resulting in strong anti-inflammation, of 83 % and 37 % highest inhibition of IL-6 and TNF-α production, respectively. Therefore, low-molecular-weight and high-sulfation-degree SPs exhibited strong anti-inflammatory activity. Specifically, K5 F2 inhibited the phosphorylation of p38, and K5 F3 suppressed the signaling pathway of p38/JNK. Overall, the sulfation degree of SPs is concluded to affect the anti-inflammatory responses.

Prophylactic IL-23 blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy

BackgroundImmune-related adverse events (irAEs), characterized by targeted inflammation, occur in up to 60% of patients with melanoma treated with immune checkpoint inhibitors (ICIs). Evidence proved that the baseline peripheral blood...

Effect of rhamnogalacturonan-I-rich polysaccharides isolated from crabapple hydrolysates on IL-1β-induced inflammation in intestinal epithelial cells

This study aimed to investigate the structural characteristics and intracellular mechanisms of polysaccharides (MP-PE-I) purified from a crabapple (Malus prunifolia) enzymatic hydrolysate (MP-PE). Activity-guided fractionation revealed that MP-PE-I was the active moiety and significantly reduced the production and gene expression of pro-inflammatory factors in interleukin (IL)-1β-treated intestinal epithelial cells (Caco-2). Moreover, MP-PE-I downregulated the phosphorylation and nuclear localization of proteins involved in the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways, as evidenced by immunoblotting and immunofluorescence analysis. In antagonistic studies with specific inhibitors of the MAPK and NF-κB pathways, IL-6 inhibition was significantly regulated by p38; IL-8 by IκBα, JNK, and p38; and monocyte chemoattractant protein-1 (MCP-1) by JNK, p38, and ERK. Additionally, MP-PE-I significantly decreased the mRNA and protein expression of IL-1 receptor type 1. Chemical and structural characteristic analyses showed that MP-PE-I is a polysaccharide rich in rhamnogalacturonan (RG)-I and plays a crucial role in intestinal immunomodulation. To our knowledge, this is the first study to demonstrate the intestinal immunomodulatory activity, intracellular mechanisms, and structural characteristics of RG-I-rich polysaccharides isolated from crabapples.

Research trends and hotspots in biologics for plaque psoriasis: A bibliometric study from 2004 to 2023

Biologics have revolutionized the management of plaque psoriasis and are flourishing. We aimed to construct a knowledge structure in this field through bibliometrics, analyze research trends and cutting-edge hotspots to inspire future research directions, and provide valuable references for clinical decisions. Publications on biologics for plaque psoriasis in the Web of Science database core collection from 2004 to 2023 were searched. Bibliometric analysis and scientific knowledge mapping were performed with R, CiteSpace, and VOSviewer software. 2,672 articles written by 9,474 authors from 67 countries were included in the study. The number of annual publications has steadily increased over the last 20 years. The most prolific countries, institutions, and authors were the United States, Novartis, and Prof. Reick K., respectively. Reference analysis categorized the research base of the field into 10 main clusters. "Efficacy" and "safety" were the most frequent keywords, and cluster analysis categorized the research in this area into four groups. Burst detection captured current hot keywords including interleukin (IL)-17 inhibitors, IL-23 inhibitors, "drug survival," "discontinuation," "Covid-19," "real-world," and "clinical features." Global publications on biologics research in plaque psoriasis have grown steadily and rapidly over the past two decades. Efficacy and safety are the highest topics of concern for researchers, and IL-17 inhibitors, IL-23 inhibitors, real-world studies, efficacy prediction, and retreatment after biologics failure or discontinuation are current research hotspots.

Anti-IL-17 monoclonal antibodies and bullous pemphigoid: treatment or causal agents? A case series and review of the literature.

Bullous pemphigoid (BP) is an autoimmune bullous disease, typically affecting the elderly, characterized by the production of autoantibodies directed against structural components of the dermal-epidermal junction. An association between BP and psoriasis has been described several times, but the mechanisms underlying this association have yet to be clearly defined. The pathophysiological mechanism underlying psoriasis may be implicated in the pathogenesis of BP, as psoriasis precedes BP in most cases; in particular, a promoting role has been hypothesized by biologic therapies, which may induce a switch from a T helper 1 (TH1)/TH17-dominant cytokine milieu, typical of patients with psoriasis, to a TH2-dominant one, typical of patients with BP. IL-17 inhibitors, in particular, have also been successfully used to treat BP in patients with psoriasis. The use of these drugs in these patients has been based on in vitro studies. However, cases of new-onset BP or relapses of BP already diagnosed in patients with psoriasis treated with biologic drugs have also been reported, and they occurred mainly in patients on anti-TNF drugs, yet very few cases with anti-IL-17A drugs have been described. We hereby describe two cases of new-onset BP in two patients treated with anti-IL-17 drugs for psoriasis.

Use of bimekizumab to treat palmoplantar psoriasis in a patient receiving treatment for disseminated tuberculosis: A Case Report.

Due to their inherent role in immunomodulation, concerns have long existed about the use of biologic therapies in patients with active tuberculosis. Most guidelines currently list active tuberculosis as an absolute contraindication to the use of immunomodulatory therapies. Contrary to this, we present a case of a patient with active, disseminated tuberculosis, safely treated with the IL-17 inhibitor bimekizumab.

Molecular mechanisms promoting long-term cytopenia after BCMA CAR-T therapy in multiple myeloma

AbstractHematologic toxicity is a common side effect of chimeric antigen receptor T-cell (CAR-T) therapies, being particularly severe among patients with relapsed or refractory multiple myeloma (MM). In this study, we characterized 48 patients treated with B-cell maturation antigen (BCMA) CAR-T cells to understand kinetics of cytopenia, identify predictive factors, and determine potential mechanisms underlying these toxicities. We observed that overall incidence of cytopenia was 95.7%, and grade >3 thrombocytopenia and neutropenia, 1 month after infusion, was observed in 57% and 53% of the patients, respectively, being still present after 1 year in 4 and 3 patients, respectively. Baseline cytopenia and high peak inflammatory markers were highly correlated with cytopenia that persisted up to 3 months. To determine potential mechanisms underlying cytopenias, we evaluated the paracrine effect of BCMA CAR-T cells on hematopoietic stem and progenitor cell (HSPC) differentiation using an ex vivo myeloid differentiation model. Phenotypic analysis showed that supernatants from activated CAR-T cells (spCAR) halted HSPC differentiation, promoting more immature phenotypes, which could be prevented with a combination of interferon γ, tumor necrosis factor α/β, transforming growth factor β, interleukin-6 (IL-6) and IL-17 inhibitors. Single-cell RNA sequencing demonstrated upregulation of transcription factors associated with early stages of hematopoietic differentiation in the presence of spCAR (GATA2, RUNX1, CEBPA) and a decrease in the activity of key regulons involved in neutrophil and monocytic maturation (ID2 and MAFB). These results suggest that CAR-T activation induces HSPC maturation arrest through paracrine effects and provides potential treatments to mitigate the severity of this toxicity.

Interleukin 23 versus interleukin 12/23 inhibitors on preventing incidental psoriatic arthritis in patients with psoriasis? A real-world comparison from the TriNetX Global Collaborative Network

BackgroundManaging psoriasis and its comorbidities, particularly psoriatic arthritis, often involves using IL-23 and IL-12/23 inhibitors. However, the comparative risk of these treatments still needs to be explored. ObjectiveThis study evaluates the risk of developing psoriatic arthritis in patients treated with IL23 inhibitors compared to IL-12/23 inhibitors. MethodsThis retrospective cohort study utilized data from the TriNetX, including adult patients diagnosed with psoriasis. Patients with IL-23 or IL-12/23 inhibitors treatment were included and propensity score matched. The primary outcome was the incidence of arthropathic psoriasis, analyzed using a Cox regression hazard model and Kaplan-Meier estimates. ResultsThe study included matched cohorts of patients treated with IL-23 inhibitors (n=2,273) and IL-12/23 inhibitors (n=2,995). Cox regression analysis revealed no significant difference in the cumulative incidence of arthropathic psoriasis between the IL-23i and IL-12/23i cohorts (p = 0.812). Kaplan-Meier estimates confirmed similar cumulative incidences of arthropathic psoriasis in both cohorts over the study period. LimitationLong-term follow-up studies are required to understand more of the effects of these interleukin inhibitors. ConclusionNo significant difference but a numerically lower risk of PsA in PsO patients treated with IL-23 inhibitors than with IL-12/23 inhibitors, underscoring their comparable efficacy in PsO management and follow-up.

Current treatment in macrophage activation syndrome worldwide: a systematic literature review to inform the METAPHOR project.

To assess current treatment in macrophage activation syndrome (MAS) worldwide and to highlight any areas of major heterogeneity of practice. A systematic literature search was performed in both Embase and PubMed databases. Paper screening was done by two independent teams based on agreed criteria. Data extraction was standardized following the PICO framework. A panel of experts assessed paper validity, using the Joanna Briggs Institute appraisal tools and category of evidence (CoE) according to EULAR procedure. Fifty-seven papers were finally included (80% retrospective case-series), describing 1148 patients with MAS: 889 systemic juvenile idiopathic arthritis (sJIA), 137 systemic lupus erythematosus (SLE), 69 Kawasaki disease (KD) and 53 other rheumatologic conditions. Fourteen and 11 studies specified data on MAS associated to SLE and KD, respectively. All papers mentioned glucocorticoids (GCs), mostly methylprednisolone and prednisolone (90%); dexamethasone was used in 7% of patients. Ciclosporin was reported in a wide range of patients according to different cohorts. Anakinra was used in 179 MAS patients, with a favourable outcome in 83% of sJIA-MAS. Etoposide was described by 11 studies, mainly as part of HLH-94/04 protocol. Emapalumab was the only medication tested in a clinical trial in 14 sJIA-MAS, with 93% of MAS remission. Ruxolitinib was the most reported JAK-inhibitor in MAS. High-dose GCs together with IL-1 and IFNγ inhibitors have shown efficacy in MAS, especially in sJIA-associated MAS. However, global level of evidence on MAS treatment, especially in other conditions, is still poor and requires standardized studies to be confirmed.

Emerging Role of Biologic Drugs Targeting IL-17 and IL-23: Pityriasis Rubra Pilaris.

Pityriasis rubra pilaris (PRP) is a rare, papulosquamous, inflammatory skin disease. PRP represents a therapeutic challenge. The rarity of this disease and its possible spontaneous remission makes the conduction and interpretation of therapeutic studies particularly difficult. Moreover, PRP not infrequently proves resistant to common topical and conventional systemic therapies. In this context, numerous biologic agents have been reported in PRP treatment. The aim of our manuscript was to review the current literature to evaluate the possible role of biologics targeting the IL17/23 axis in PRP management. Recent cases in the literature have highlighted the use of several promising drugs: IL-17 inhibitors, IL-23 inhibitors, and the IL-12/23p40 inhibitor ustekinumab. However, it should be noted that all these drugs are approved for moderate-to-severe plaque psoriasis and their use in PRP is off label. The treatment of PRP is based on clinical experience, case reports or case series reported in the literature, as randomized controlled trials are difficult to conduct due to the rarity of the condition. Despite data on the efficacy of drugs targeting IL-17 and IL-23 being promising, they are still limited. Certainly, further studies are desirable to better characterize PRP and establish shared guidelines.

Improvement of Vestibular Neuritis in a Patient with Psoriatic Arthritis following Ixekizumab Administration

Psoriatic arthritis (PsA) is a chronic inflammatory condition commonly affecting peripheral joints and the skin. Recent studies have shown an association between PsA and vestibulocochlear dysfunction. Here, we present the case of a 43 year-old male with a history of controlled psoriasis (Pso) and PsA who presented with sudden-onset severe vertigo, nausea, and vomiting. Diagnostic evaluation ruled out a central etiology, leading to a diagnosis of vestibular neuritis of unknown origin. Despite minimal improvement with conventional medications, the patient experienced significant relief from vertigo symptoms following treatment with ixekizumab, an IL-17 inhibitor used to manage his PsA and Pso. This case highlights a potential therapeutic effect of biological agents on vestibular dysfunction associated with PsA. Future research in this area may provide insights into novel treatment strategies for vestibular symptoms in patients with PsA.

Clinical outcomes of immunomodulation therapy in immunocompromised patients with severe Covid-19 and high oxygen requirement

Covid-19 disease is implicated in increased mortality among immunocompromised patients. The JAK inhibitor, baricitinib (bar), or the IL-6 inhibitor, tocilizumab (toc), demonstrated a survival benefit in patients with severe disease.However, evidence supporting their use in immunocompromised patients with severe Covid-19 is scarce.We aimed to assess clinical outcomes of bar/toc treatment in immunocompromised patients. A multi-center registry of consecutive immunocompromised patients hospitalized due to severe Covid-19 during the Omicron variant dominance period. After excluding patients who did not require high oxygen supply, patients treated with bar/toc were compared to patients treated by standard of care (SOC). Primary outcome was in hospital mortality. Secondary outcomes were 30 and 60 day mortality, super-infection and thromboembolic events. Among an overall 228 immunocompromised patients hospitalized in six Israeli hospitals with severe Covid-19, 112 patients required high oxygen support, of whom 48 (43%) were treated with bar/toc. In-hospital mortality rates were exceptionally high and did not significantly differ between bar/toc and SOC treated patients (62.5% vs. 64.1%, p = 1.0). A logistic regression analysis revealed that advanced age and incomplete vaccination were predictors of in-hospital mortality. Patients treated with bar/toc had no excess of suspected super-infection (62.8% vs. 60.7%, p = 0.84) or thromboembolic events (8.3% vs 3.1%, p = 0.39). In immunocompromised patients with severe Covid-19 and a high oxygen demand, bar/toc therapy was not associated with reduced mortality or with a higher rate of associated complications, compared to SOC. Larger prospective studies should better address efficacy and safety.