Treatment of pemphigus vulgaris and foliaceus with efgartigimod, a neonatal Fc receptor inhibitor: a phase II multicentre, open-label feasibility trial.

BACKGROUND: Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoimmune disorders triggered by IgG autoantibodies against mucosal and epidermal desmogleins. There is an unmet need for fast-acting drugs that enable patients to achieve early sustained remission with reduced corticosteroid reliance. OBJECTIVES: To investigate efgartigimod, an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor, thereby reducing serum IgG levels, for treating pemphigus. METHODS: Thirty-four patients with mild-to-moderate pemphigus vulgaris or foliaceus were enrolled in an open-label phase II adaptive trial. In sequential cohorts, efgartigimod was dosed at 10 or 25 mg kg-1 intravenously with various dosing frequencies, as monotherapy or as add-on therapy to low-dose oral prednisone. Safety endpoints comprised the primary outcome. The study is registered at ClinicalTrials.gov (identifier NCT03334058). RESULTS: Adverse events were mostly mild and were reported by 16 of 19 (84%) patients receiving efgartigimod 10 mg kg-1 and 13 of 15 (87%) patients receiving 25 mg kg-1 , with similar adverse event profiles between dose groups. A major decrease in serum total IgG and anti-desmoglein autoantibodies was observed and correlated with improved Pemphigus Disease Area Index scores. Efgartigimod, as monotherapy or combined with prednisone, demonstrated early disease control in 28 of 31 (90%) patients after a median of 17 days. Optimized, prolonged treatment with efgartigimod in combination with a median dose of prednisone 0·26 mg kg-1 per day (range 0·06-0·48) led to complete clinical remission in 14 of 22 (64%) patients within 2-41 weeks. CONCLUSIONS: Efgartigimod was well tolerated and exhibited an early effect on disease activity and outcome parameters, providing support for further evaluation as a therapy for pemphigus.

Beneficial properties of single-domain antibody fragments for application in immunoaffinity purification and immuno-perfusion chromatography.

We explored the possibility to apply single-domain antibodies from Camelidae for immunoaffinity purification of the ice structuring protein (ISP) from Lolium perenne, which modifies ice crystal growth and therefore has potential application in medicine, biotechnology, agriculture and (frozen) foods. Using phage display together with an appropriate selection method, a group of candidate fragments was isolated from a llama-derived immune library. Affinity chromatography using a purposely selected antibody coupled to a matrix yielded a completely pure and functional ISP. Due to the extreme refolding capabilities and physical stability of single-domain antibodies, the affinity matrix could be regenerated more than 2000 times without loss of capacity, while the fragment's monomeric nature permitted an efficient elution of antigen. The results of this study show that highly pure proteins can be recovered from biological material in a single-step process.

Patients with ankylosing spondylitis and healthy relatives do not show increased small intestinal permeability with the lactulose-mannitol test.

Small intestinal permeability was measured in 71 subjects: 26 (24 B27+) patients with ankylosing spondylitis (AS); 20 healthy first degree relatives (13 B27+); 6 patients with active Crohn's disease and 19 healthy controls. We determined the urinary excretion ratio of two ingested sugar probes, lactulose (10 g) and mannitol (0.5 g) by gas-liquid chromatography. The median lactulose/mannitol excretion ratio in AS patients (0.0099) and relatives (0.0090) was not significantly different from the median ratio in healthy controls (0.0095). HLA status or use of NSAIDs did not significantly influence the results. In patients with Crohn's disease, on the other hand, the median lactulose/mannitol ratio (0.021) was significantly increased in comparison to healthy controls (0.0095). Our results confirm that the lactulose-mannitol test can be used to demonstrate increased intestinal permeability in Crohn's disease. For patients with AS and their relatives the lactulose-mannitol test may not be sufficiently sensitive. Alternatively, significantly increased permeability may not occur in most patients with AS.

Determination of low levels of bupivacaine (Marcaine) in plasma during epidural analgesia.

A rapid method is described for the determination of plasma levels of bupivacaine used for epidural analgesia during childbirth. Data obtained in a clinical study are also given.

A gas chromatographic method for the estimation of phenprocoumon, 3-(1-phenyl-propyl)-4-hydroxycoumarin (Marcoumar, Liquamar), in human serum or plasma.

A rapid and reliable gas-chromatographic method is described for the estimation of phenprocoumon from human serum or plasma. No interference was found from other usual oral anticoagulant drugs. The method can be used for therapeutic and toxic levels. The appearance of two volatile derivatives of phenprocoumon (in constant ratio) is discussed.

Quantitative determination of sodium-o-[(2,6-dichlorophenyl)-amino]phenylacetate (diclofenac) in human blood plasma or serum.

A rapid method for the estimation of sodium-(o-[(2,6-dichlorophenyl)-amino]-phenyl)-acetate (diclofenac-Na, Voltaren) used in the treatment of rheumatic diseases, in human blood plasma is described. The substance is extracted from acidified plasma with dichloromethane and acetylated after evaporation of the organic solvent, whereupon quantitation is performed by gas-liquid chromatography on a 10% OV-17 column, F.I. detection.