Non-infectious uveitis (NIU) encompasses a range of conditions marked by inflammation within various layers of the eye. NIU is a significant contributor to irreversible vision loss among the working-age population in developed countries. The aim of treating uveitis is to manage inflammation, prevent its recurrences and to restore or salvage vision. Presently, the standard treatment protocol for NIU involves initiating corticosteroids as the primary therapeutic agents, although more aggressive approaches and steroid sparing agent may be necessary in certain cases. These advanced treatments option include synthetic immunosuppressants like antimetabolites, calcineurin inhibitors and alkylating agents. For patients who exhibit an intolerance or resistance to corticosteroids and conventional immunosuppressive therapies, biologic agents have emerged as a promising alternative. Notably, among the biologic treatments evaluated, TNF-α inhibitors, anti-CD20 therapy and alkylating agents have shown considerable efficacy. In this review, we delve into the latest evidence surrounding the effectiveness of biologic therapy and introduce novel therapeutic strategies targeting immune components as potential avenues for advancing treatment of NIU.

Ankylosing spondylitis (AS) is a challenging disease, characterized by chronic inflammation and structural damage primarily affecting the axial skeleton, while extra-articular manifestations may also appear. This results in the deterioration of patients\' quality of life. Over the past few decades, tumor necrosis factor-α (TNF-α) inhibitors have revolutionized the management of AS, offering substantial relief from symptoms and improving patient outcomes. The aim of this review is to assess the efficacy of TNF-α inhibitors in patients with active AS. A search was performed in the PubMed database using the following keywords: (\"TNF alpha inhibitors\" OR \"anti TNF-a\" OR \"TNF-a inhibitors\" OR \"anti TNF-alpha\" OR \"Etanercept \" OR \"Golimumab\" OR \"Infliximab\" OR \"Certolizumab pegol\" OR \"Adalimumab\") AND \"ankylosing spondylitis\". The search was completed in February 2024, and 35 studies were included in this review following PRISMA guidelines. The findings reveal evidence supporting the efficacy of TNF-α inhibitors in reducing inflammation, preventing structural damage, and enhancing overall well-being in AS patients. Overall, TNF-α inhibitors have emerged as a cornerstone in the therapeutic algorithm against AS with a very satisfactory safety profile.

BACKGROUND: Due to the increasing prevalence of immune-mediated diseases such as psoriasis, lichen planus, rheumatoid arthritis and inflammatory bowel disease, dermatologists have turned to new biologic drugs known as DMARDs (disease-modifying anti-rheumatic drugs) in recent years.
METHODS: In this study, we evaluate the immune-mediated dermatological side effects of DMARDS by reviewing and analyzing previous peer-reviewed research on the effects of TNF-α inhibitors in the treatment of skin diseases, as well as adverse effects of these drugs and some of the main causes of these effects.
CONCLUSIONS: DMARDs are very effective in improving control of the above diseases. TNF-α inhibitors are an important group of DMARDs that are widely used. The paradoxical adverse events (PAEs) associated with the use of TNF-α inhibitors are divided into three categories: true paradoxical, borderline paradoxical, and non-paradoxical. True PAEs include conditions for which TNF-α inhibitors are approved for treatment. Borderline PAEs are considered to occur with this class of drugs for which there is no definite approval but for which there is sufficient evidence. Although these events are rare, early recognition of the accused drug and appropriate decision-making may prevent progression of complications and irreversible side effects.

Erythromelalgia is a rare syndrome with a generally unknown etiology. Whether primary or secondary, this condition is characterized by paroxysmal episodes of erythema, pain, and heat in the extremities. We report two cases of erythromelalgia occurring after the initiation of treatment with infliximab. The first case involves a 38-year-old patient who had been followed since August 2022 for ileocolonic Crohn\'s disease classified as A2L3B3 according to the Montreal classification, which was resistant to treatment and required infliximab therapy. Two months after the first infusion of infliximab, the patient developed symptoms of erythromelalgia. After ruling out other potential causes through an etiological assessment and conducting a pharmacological investigation, infliximab was considered the most likely cause. Infliximab was discontinued, and symptomatic treatment was initiated, including vascular laser sessions. The patient showed significant clinical improvement. In the second case, a 16-year-old patient with ileocolonic Crohn\'s disease classified as A1L3B3 according to the Montreal classification was treated with ileocecal resection and received an infusion of infliximab. Sixteen days after the second infusion, she developed clinical symptoms of erythromelalgia. The etiological assessment was inconclusive. Due to a strong suspicion of erythromelalgia secondary to tumor necrosis factor (TNF) alpha inhibitor therapy, infliximab was replaced with ustekinumab. The patient also received symptomatic treatment, and her clinical condition improved, marked by the disappearance of pain.

Hidradenitis suppurativa (HS) is a disease with a poor prognosis, often misinterpreted as an infection, with the highest impact on the patient\'s quality of life among all the assessed dermatological diseases. The main aim of this study was to compare various therapeutic interventions that are currently available for the treatment of HS. The pathogenesis of HS is not well understood, but it is mostly multifactorial involving a number of factors like genetic factors, androgens, local immunity, microflora, smoking, and obesity. Despite limited evidence on their effectiveness, topical antibiotics and antiseptics are commonly employed. Due to the colonization of bacteria and the presence of biofilms in the sinus tracts formed by HS lesions, systemic antibiotics are commonly employed as the primary form of therapy. In females with HS who experience menstrual flares or display symptoms of polycystic ovary syndrome, hormonal agents are often considered to be a viable and effective therapeutic option. At present, the sole treatment approved by both the Food and Drug Administration and the European Medicines Agency for addressing moderate to severe HS is adalimumab, an antibody that targets tumor necrosis factor alpha. Many surgical procedures in the management of HS aim to address inflammation by eliminating the affected folliculo-pilosebaceous unit, sinus tracts, and associated debris to impede further progression and scarring. HS continues to pose a considerable treatment challenge, necessitating a comprehensive approach for patients. However, the available evidence for most of these treatments is limited, indicating the need for more extensive research to identify the most effective interventions for managing HS.

There are few cases in the literature demonstrating vasculitis induced by tumor necrosis factor-α. There exist even fewer cases of systemic inflammation involving the skin, nerves, and kidneys. Here, we present a novel case of a 27-year-old man with Crohn disease refractory to multiple medications, most recently treated with infliximab. He presented with a 3-week history of non-blanching palpable petechial rash involving his bilateral extremities and right upper extremity as well as lesions with black eschar around his ankles. He was found to have refractory cutaneous small vessel vasculitis, nephrotic range proteinuria, and small fiber neuropathy. This case describes the evaluation and treatment of systemic small vessel vasculitis in the setting of infliximab therapy.

Multiple sclerosis (MS) is the most common disabling disease of the central nervous system (CNS) with a progressive neurodegenerative pattern. It is characterized by demyelination of white matter in CNS and apoptosis of oligodendrocytes. Tumor necrosis factor (TNF) alpha is a major cytokine in the pathogenesis of MS. However, the failure of TNF alpha inhibitors in preclinical and clinical trials disapproved of their use in MS patients. Nevertheless, failures and misses sometimes open avenues for new hits. In the later years, it was discovered that TNF signaling is mediated via two different receptors, TNFR1 and TNFR2, both of which have paradoxical effects. TNFR1 mediates demyelination and apoptosis, while TNFR2 promotes remyelination and neuroprotection. This explained the cause of the failure of non-selective TNF alpha-blockers in MS. It also enlightened researchers that repurposing the previously formulated non-selective TNF alpha-blockers using a receptor-selective approach could lead to discovering novel biologic agents with a broader spectrum of indications and better safety profiles. This review focuses on a novel premier TNFR1 blocker, atrosab, which has been tested in animal models of MS, experimental autoimmune encephalomyelitis (EAE), where it demonstrated a reduction in symptom severity. The early promise shown by atrosab in preclinical studies has given us hope to find another revolutionary drug for MS in the future. Clinical trials, which will finally decide whether this drug can be used as a better therapeutic agent for MS or not, are still going on, but currently, there is no approved evidence regarding efficacy of these agents in treating MS.

The aim of this cohort study was to evaluate the long-term effects of TNF inhibitors (TNFis) on BMD and the incidence of vertebral fractures (VFxs) in patients with ankylosing spondylitis (AS). Consecutive patients with active AS with TNFi treatment duration up to 4 years with available DXA scans and spine X-rays were included. BMD (classified according to the WHO criteria for osteoporosis) of the hip and lumbar spine, the VFx (classified as a Genant score >1/>20% height loss), and radiological progression (modified stoke ankylosing spondylitis spinal score [mSASSS]) scores were obtained at baseline and at 4 years of TNFi treatment. Overall, 135 AS patients were included. At baseline, 40.1% of patients had low BMD of the hip and 40.2% of the lumbar spine. This decreased to 38.1% (p = 0.03) with low hip BMD and 25.3% (p < 0.001) of the lumbar spine BMD after 4 years of TNFi treatment. VFxs were present at baseline in 11.1% of the 131 patients, which increased to 19.6% after 4 years of TNFi treatment. A Genant score ≥2, was found at baseline in 3 out of 14 VFx (21.4%) patients, which increased to 7 out of 27 VFx (25.9%) patients after 4 years. All disease activity parameters-the ankylosing spondylitis disease activity scale, the C-reactive protein, the erythrocyte sedimentation rate, and the bath ankylosing spondylitis disease activity index-decreased significantly (p < 0.001). The mean radiological progression (n = 80) increased significantly from a median mSASSS of 4.0 (1.5 to 16.0) at baseline to 6.5 (2.1 to 22.9) after 4 years of TNFi treatment (p < 0.001). Despite the improvement in BMD and the decrease in disease activity, we still found new VFxs, an increase in severity in the number and grade of VFxs, and radiographic progression during 4 years of treatment with TNFis in AS patients with long disease duration. © 2019 American Society for Bone and Mineral Research.

Autoimmune hepatitis (AIH) is a cause of chronic, immune-mediated liver injury which without treatment may progress to end-stage liver disease. The disease state, characterized by elevations in liver enzymes, autoantibodies, and interface hepatitis on histology, has been noted to be induced by a wide range of insults. Medications, most commonly minocycline and nitrofurantoin, have long been established as potential inducers of AIH. Recently, biologics, powerful immune-modulators, have also been reported to induce AIH. We conclude that there is an association between administration of biologics in the development of AIH, and whether the relationship is causal will require appropriate studies in the future.

BACKGROUND: Ankylosing spondylitis is a chronic immune-mediated disease affecting the sacroiliac joints and the spine manifesting with new bone formation and osteopenia. Over the past decade, tumour necrosis factor alpha (TNF-α) inhibitors (TNFi) have become the cornerstone for therapy in improving functional outcomes, and decreasing disease activity in patients with a marginal benefit from non-steroidal anti-inflammatory (NSAID) therapy. At this time, it remains to be determined whether these agents decrease new bone formation, although some studies have recently suggested that. Areas covered: In this review we discuss the factors that favour a good response to these agents both initially and during maintenance, and some of the more recent studies outlining strategies for dose reduction. Expert commentary: Finally, we discuss the importance of using more objective tools for disease activity, such as magnetic resonance imaging, as a complementary tool for clinical assessments in both predicting responses to treatment but also in selecting patients most suited for targeted therapy.