Cost evolution of biological drugs in rheumatoid arthritis patients in a tertiary hospital: Influential factors on price

ObjectiveTo assess the evolution of cost per patient/year and the cost per patient/year/drug in patients with rheumatoid arthritis (RA) receiving biological treatments. To analyze and quantify the factors influencing this evolution, such as the optimization of the biological drugs, the use of biosimilars, and official discounts and discounts obtained after negotiated procedures. In addition, to assess specific clinical parameters of disease activity in these patients.MethodsRetrospective, observational study conducted in a Spanish tertiary hospital. Adult patients diagnosed with RA under treatment from 2009 to 2017 were included.Results320, 270 and 389 patients were included in 2009, 2013 and 2017, respectively. The patient/year cost decreased from 10,789€ in 2009, 7491€ in 2013 to 7116€ in 2017. In 2017, due to the established competition, discounts of 14% and 29.5% were achieved on etanercept and its biosimilar; 11.5%, 17.8%, 17.9%, 17.3% on adalimumab, certolizumab, golimumab and tocilizumab IV respectively, and 24.6% and 43.1% on infliximab and its biosimilar. The percentage of patients optimized in 2017 was 35.2%. The annual saving in 2017 was 1,288,535€ (830,000€ due to dose optimization and/or administration regimens, 249,666€ corresponding to 7.5% of the official discount and 208,868€ after negotiated procedures).ConclusionThe annual cost per patient in RA decreased considerably due to different factors, such as discounts on the purchase of drugs due to official discounts and negotiated procedures, together with the optimization of therapies, the latter being the factor that contributed most to this decrease.     

A novel splice-site variant in CDH23 in a patient with Usher syndrome type 1

ABSTRACT

Background: Gene editing has shown huge potential in correcting aberrant splicing and Cas13 has been identified as being particularly suitable for targeting RNA. It has therefore become increasingly important to highlight new splice site mutations that may be correctable, particularly in genes that are too large to be encoded by AAV vectors. About 20% of Usher Type 1 cases are caused by mutations in CDH23.

Purpose: To report a novel splice site mutation of CDH23 associated with Usher Type 1D.

Materials and Methods: Case report.

Results: A 35-year-old Caucasian female who is congenitally deaf with vestibular dysfunction presented with visual acuity of 6/12 in both eyes. Fundus examination revealed findings typical of retinitis pigmentosa with foveal preservation of photoreceptor layer. Next generation sequencing analysis revealed a novel homozygous variant, c.9319 + 1G>T in CDH23 consistent with the diagnosis of Usher Syndrome Type 1D. The c.9319 + 1G>T variant is predicted to affect splicing at the exon 65/intron 65 boundary, which highly likely leads to complete skipping of exon 65.

Conclusions: We describe a case of a typical Usher Syndrome Type 1D caused by a novel splice site variant in CDH23. Currently there are no treatments for CDH23 related retinal degeneration, partly because the cDNA size of 10kb is too large for AAV vector gene augmentation therapy. Alternative strategies include CRISPR-Cas9 adenine base editors and RNA editing with CRISPR-Cas13. Single-nucleotide editing represents a promising approach for targeting this variant in CDH23 to restore the wildtype splice donor site at this position.