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Janus kinases inhibitors (anti-JAKs), including tofacitinib, baricitinib, upadacitinib, and filgotinib, represent a new class of synthetic targeted drugs for the treatment of rheumatoid arthritis (RA). In this review, the risk of active tuberculosis (TB) occurrence in patients receiving anti-JAKs was assessed. The literature on this topic, updated to 29 February 2020 was reviewed. Overall, 40 reports (22 tofacitinib, 10 baricitinib, 5 upadacitinib, 3 filgotinib) were examined. A low frequency, not exceeding 0.25%, of active TB cases in patients were exposed to anti-JAKs. Only 1 of 89 recorded cases in tofactinib and baricitinib exposure occurred in countries at intermediate or high TB risk, and most of the cases probably were due to first mycobacterium tuberculosis (Mtb) exposure. Although no cases were observed in patients receiving upadacitinib and filgotinib, long-term trials and data from real-life are required to more precisely address the TB risk associated with the two drugs.Discussion on the TB risk associated with anti-JAKs, and on the need for accurate evaluation of host-related risk factors in high risk countries.Available data on anti-JAKs suggest a negligible risk of active TB occurrence in low endemic areas.

Monoclonal antibody (mAb) therapy has been previously exploited for viral infections, such as respiratory syncytial virus pneumonia and Ebolavirus disease. In the ongoing COVID-19 pandemic, early signals of efficacy from convalescent plasma therapy have encouraged research and development of anti-SARS-CoV-2 mAbs. While many candidates are in preclinical development, we focus here on anti-SARS-CoV-2 neutralizing mAbs (or mAb cocktails) that represent the late-stage clinical pipeline, i.e., those currently in Phase 2 or Phase 3 clinical trials. We describe the structure, mechanism of action, and ongoing trials for VIR-7831, LY-CoV555, LY-CoV016, BGB-DXP593, REGN-COV2, and CT-P59. We speculate also on the next generation of these mAbs.

Crohn's disease (CD) is an inflammatory bowel disease of unknown etiology. However, increasing evidence suggests Mycobacterium avium subspecies paratuberculosis (MAP) as a putative causative agent: 1) MAP is the etiological agent of Johne's disease, a granulomatous enteritis affecting ruminants, which shares clinical and pathological features with CD; 2) MAP has been detected in tissues and blood samples from CD patients; 3) case reports have documented a favorable therapeutic response to anti-MAP antibiotics. Area covered: This review provides an appraisal of current information on MAP characteristics, diagnostic methodologies and emerging drug treatments. The authors focus on RHB-104, a novel oral formulation containing a fixed-dose combination of clarithromycin, clofazimine and rifabutin, endowed with synergistic inhibitory activity on MAP strains isolated from CD patients. Expert opinion: Based on encouraging in vitro data, RHB-104 has entered recently the clinical phase of its development, and is being investigated in a randomized, placebo-controlled phase III trial aimed at evaluating its efficacy and safety in CD. Provided that the overall clinical development will support the suitability of RHB-104 for inducing disease remission in CD patients with documented MAP infection, this novel antibiotic combination will likely take a relevant position in the therapeutic armamentarium for CD management.

Introduction: Psoriasis is a chronic inflammatory skin disorder pathogenically mediated by multiple cytokines, including interleukin (IL)-23, IL-17, and TNF. An emerging class of therapeutics that selectively blocks IL-23 has been developed. Among these new agents, risankizumab is now being investigated in phase III clinical trials, and the preliminary data are promising in inducing an excellent clinical response. Areas covered: This review aims to describe the pathogenic role of IL-23 in psoriasis and to collect clinical data related to the efficacy and safety of risankizumab, an anti-IL-23p19 agent, in the treatment of psoriasis. Expert opinion: Risankizumab showed high response rates in reaching complete or almost complete clearance of psoriasis. When compared to other similarly effective drugs, it may show some advantages related to its mechanism of action (direct blockade of the main pathogenic pathway), safety (no impact on the immune surveillance against Candida infection), therapeutic regimen (every-12-week injections), and effectiveness in the treatment of immune-mediated psoriasis comorbid conditions, such as psoriatic arthritis and Crohn's disease.

Proton pump inhibitors (PPIs) display a number of limitations and unmet clinical needs that have prompted the development of novel drugs to improve the outcomes of acid-related diseases, including the eradication of H. pylori. In this context, a new synthesized potassium-competitive acid blocker (P-CAB), vonoprazan, showed higher suppression of gastric acid secretion. Areas covered: This review discusses the current knowledge regarding the efficacy of vonoprazan in the treatment of acid-related diseases, with a particular focus on its use in Helicobacter pylori eradication. Expert opinion: Vonoprazan showed some advantages over PPIs in terms of the pharmacokinetic and pharmacodynamic profile: fast onset of action without requiring acid activation and specific administration timing, more potent and prolonged inhibition of acid secretion, including a better nighttime acid control, and a less antisecretory variability. Recent evidence suggests that vonoprazan can be preferred to PPIs as maintenance therapy for reflux esophagitis and eradication of Helicobacter pylori owing to its stronger antisecretory effect. Moreover, vonoprazan displays favorable safety and tolerability profiles, even though long-term studies on the effects of vonoprazan are required.

About 30-40% of GERD patients report an inadequate response to proton pump inhibitors (PPIs) due to their suboptimal pharmacological profiles. Recently, a new synthesized P-CABs, vonoprazan, showed higher suppression of gastric acid secretion as compared to lansoprazole. Areas covered: This review provides an update on the pharmacokinetic properties of vonoprazan and their correlates with pharmacodynamics; preliminary data on the therapeutic efficacy of vonoprazan as compared to lansoprazole in GERD patients Expert opinion: At variance from all available PPIs, vonoprazan acts directly on H+,K+-ATPase irrespectively of its activity, providing a fast onset of action without requiring acid activation and specific administration timing. Clinical and pharmacological investigations have confirmed a more rapid, potent and prolonged inhibition of acid secretion, including a better nighttime acid control, and a less antisecretory variability, as compared with PPIs. Preliminary data in patients with erosive esophagitis (EE) have shown the non-inferiority of vonoprazan to lansoprazole in terms of symptom relief and healing rate. Since these pharmacokinetic advantages, it is expected that it will have a significant favorable impact on GERD management. However, the clinical use of vonoprazan raises also some issues about its efficacy and safety in the long-term that deserve verification and careful investigation.

Transurethral resection (TUR) syndrome, resulting from dilutional hyponatraemia for excessive absorption of irrigating fluid, represents the most relevant complication of transurethral resection of prostate (TURP). Ethanol is used as a tracer in the irrigant solution to monitor fluid absorption with a breathalyser. An unusual case of transient acute liver failure complicating TUR syndrome is reported. A 54-year-old male patient, without risk factors for the development of toxic hepatitis, was subjected to TURP for treatment of benign prostatic hyperplasia. Fluid absorption (2275 ml), estimated by breathalyser, exceeded maximum allowed absorption (2000 ml) only at the end of the surgical intervention. No signs of possible toxicity were evident in the few hours following the intervention. About 10 h after the end of TURP, the patient developed sweating, vomiting and diarrhoea. Laboratory analysis revealed severe hyponatraemia (116 meq/l) with signs of severe liver impairment (total bilirubin 5.8 mg/dl, alanine aminotransferase 56,500 U/l, aspartate aminotransferase 32,700 U/l), kidney failure (serum creatinine 1.93 mg/dl) and serum ethanol levels of 219 mg/dl (0.2%). The patient was treated with acetylcysteine 150 mg/kg i.v. and furosemide 50 mg i.v. Liver and renal functions improved in few days and recovered completely within 30 days. The TUR syndrome observed in this case was probably extravascular in nature, and could have been identified and prevented by measuring ethanol levels 10 min after ending the surgical procedure. The performance of such a test should be strongly recommended to all surgeons. The clinicians attributed the development of liver impairment in this case to ethanol toxicity. However, further studies are warranted to confirm whether hepatic injury can represent a possible complication of TUR syndrome when ethanol solution is used as irrigant fluid.

Inhaled corticosteroids, long-acting beta2-adrenoceptor agonists, and leukotriene receptor antagonists are widely used for treatment of asthma. Inhaled corticosteroids are recommended as first-line therapy, whereas long-acting beta2-adrenoceptor agonists and leukotriene receptor antagonists are indicated as add-on therapy in patients not adequately controlled with corticosteroids alone. A number of studies have investigated the efficacy of combinations of these drugs in asthma, but several issues concerning the safety of these treatments are highly debated. This review provides a critical appraisal of the tolerability profiles of long-acting beta2-agonists and leukotriene receptor antagonists used in combination with inhaled corticosteroids for the treatment of asthma.

The ecto-5'-nucleotidase/CD73 enzyme plays a pivotal role in generating an adenosine-enriched immunosuppressed and pro-angiogenic niche supporting cancer development. The targeting of CD73 leads to reorganization of tumor microenvironment, shaping the phenotype of the infiltrating T cells. The development of CD73 monoclonal antibodies offers a promising new avenue for antineoplastic treatment.