IncobotulinumtoxinA for Post-stroke Upper Limb Spasticity in Neutralizing Antibody-positive Patients after Botulinum Toxin Therapy: A Report of Two Cases.

Background: Botulinum toxin type A is an effective treatment widely used to address post-stroke spasticity. Long-term repeated treatment with botulinum toxin type A may result in reduced efficacy due to the induction of neutralizing antibodies. Based on data from a phase 3 study of incobotulinumtoxinA for post-stroke upper limb spasticity, we describe the therapeutic response to botulinum toxin type A treatment in two neutralizing antibody-positive patients previously treated with other preparations of botulinum toxin type A. Case: Two patients (a 65-year-old woman and a 36-year-old woman) with post-stroke upper limb spasticity were previously treated with onabotulinumtoxinA, and neutralizing antibodies were detected in their sera at baseline using the mouse hemidiaphragm assay. After onabotulinumtoxinA had been discontinued for at least 16 weeks, incobotulinumtoxinA (400 U) was administered in three or four injection cycles. Good therapeutic responses, manifested by a reduction of 1-2 points on the modified Ashworth scale, were noted after each injection. The patients' sera remained positive for neutralizing antibodies throughout the incobotulinumtoxinA treatment period. Discussion: These patients, who were previously treated with onabotulinumtoxinA and were neutralizing antibody positive throughout the clinical study period, showed stable therapeutic responses following incobotulinumtoxinA treatment. IncobotulinumtoxinA could be initiated for patients with neutralizing antibodies induced by onabotulinumtoxinA.

Preoperative and long-term efficacy and safety of lanreotide autogel in patients with thyrotropin-secreting pituitary adenoma: a multicenter, single-arm, phase 3 study in Japan.

Somatostatin analogs are recommended for pharmacotherapy of TSH-secreting pituitary adenoma (TSHoma). A multicenter clinical trial was conducted to evaluate the efficacy and safety of lanreotide autogel treatment for TSHoma. A total of 13 Japanese patients with TSHoma were enrolled from February to December 2018 and treated with lanreotide autogel 90 mg every 4 weeks, with dose adjustments to 60 mg or 120 mg. Analysis was performed on data from patients receiving preoperative treatment (n = 6) up to 24 weeks and from those receiving primary or postoperative treatment (n = 7) up to 52 weeks. The primary efficacy endpoints were serum concentrations of TSH, free triiodothyronine (FT3), and free thyroxine (FT4). The secondary efficacy endpoints were pituitary tumor size and clinical symptoms. The serum concentrations of TSH, FT3, and FT4 decreased with treatment, and euthyroid status was maintained until final assessment. FT4 at final assessment was within reference ranges in 10/13 patients. The median (interquartile range) percent change in pituitary tumor size from baseline at final assessment was -23.8% (-38.1, -19.8). The clinical symptoms were also improved. The patients receiving preoperative treatment did not develop perioperative thyroid storm. Regarding safety, adverse events were observed in 12/13 patients, but none discontinued treatment. The common adverse events were gastrointestinal disorders (12/13 patients) and administration site reactions (5/13 patients). Lanreotide autogel may be effective for controlling thyroid function and reducing the pituitary tumor size, and is tolerable in patients with TSHoma (Japic Clinical Trials Information; JapicCTI-173772).