Persistence and Use of Ixekizumab in Patients with Psoriatic Arthritis in Real-World Practice in Spain. The PRO-STIP Study.

INTRODUCTION: Ixekizumab (IXE) is an IgG4-type monoclonal antibody targeting IL-17A indicated alone or in combination with methotrexate, for the treatment of active psoriatic arthritis (PsA) in adult patients with insufficient response or with intolerance to one or more disease-modifying anti-rheumatic drug (DMARD) therapy. The PRO-STIP study aimed to describe persistence, patient characteristics, treatment patterns, and effectiveness in patients with PsA receiving IXE in a real-world clinical setting in Spain. METHODS: This was an observational, multicentric, retrospective, longitudinal study in adult PsA patients who started IXE between January 2019 and December 2020, with at least 24 weeks of follow-up. A descriptive analysis of patient characteristics and treatment patterns was performed. The primary objective, treatment persistence, was estimated by Kaplan-Meier survival curve. Effectiveness was evaluated by Disease Activity in Psoriatic Arthritis (DAPSA) scores at baseline and at 12 and 24 weeks. RESULTS: Eighty-nine patients met the selection criteria (55.1% women and mean age 51.5 years). The median time from PsA diagnosis to starting IXE was 7.7 years (IQR 3.4-14.6). Prior to IXE, 95.5% patients had been treated with at least one biologic or targeted synthetic DMARD (b/tsDMARD). The observed persistence rates were 95.5%, 84.3% and 68.5% at 24, 48, and 104 weeks, respectively. The median persistence was not reached in the study period (mean persistence, 86.9 [95% CI 80.6-93.2] weeks). Twenty-eight (31.5%) patients discontinued IXE, 19 patients (21.3%) due to loss of effectiveness and two patients (2.2%) due to adverse events. In patients receiving treatment and with available effectiveness assessment (n = 24), DAPSA decreased significantly from baseline 23.7 (95% CI 19.5-27.9) to 14.8 (95% CI 10.5-19.2) at 12 weeks (p = 0.005) and 14.3 (95% CI 11.1-17.4) at 24 weeks (p = 0.004). CONCLUSIONS: PsA patients treated with IXE in a real-world setting show high treatment persistence through 104 weeks and improvements in disease activity after treatment initiation. This suggests that IXE could be an effective treatment for patients with PsA. RETROSPECTIVELY REGISTERED: Date of registration: 25th May 2021.

Risk factors for the development of chronic back pain after percutaneous vertebroplasty versus conservative treatment.

In a recent randomized controlled trial comparing vertebroplasty (VP) versus conservative treatment (CT) in patients with symptomatic vertebral fractures (VF), we observed the development of chronic back pain (CBP) in nearly one-quarter of patients. The aim of this study was to identify the risk factors related to the development of severe CBP in these subjects. We evaluated risk factors including visual analog scale (VAS) at baseline and during the 1-year follow-up, age, gender, symptom onset time, number, type and severity of VF at baseline, number of vertebral bodies treated, incident VF, and antiosteoporotic treatment, among others. CBP was considered in patients with VAS ≥ 7 at 12 months. 91/125 patients completed the 12-months follow-up. CBP was observed in 23% of VP-treated patients versus 23% receiving CT. Patients developing CBP after VP showed a longer symptom onset time (82% ≥ 4 months in VP vs. 40% in CT, P = 0.03). On univariate analysis, female gender (OR 1.52; 95% CI 1.47-1.57, P < 0.0001), multiple acute VF (OR 1.79; 95% CI 1.71-1.87, P < 0.0001), VAS ≥ 7 two months after treatment (OR 11.04; 95% CI 6.71-18.17, P < 0.0001), and type of antiosteoporotic drug (teriparatide) (OR 0.12; 95% CI 0.03-0.60, P = 0.0236) were risk factors of CBP development in both groups. In the multivariate analysis, the main risk factors were baseline and post-treatment VAS ≥ 7, longer symptom onset time, and type of antiosteoporotic treatment. In conclusion, 23% of patients with symptomatic osteoporotic VF developed severe CBP independently of the type of treatment. Symptom onset time before VP and persistence of severe CBP after treatment were the main factors related to CBP with teriparatide treatment decreasing the risk of this complication.

[Effectiveness of vertebroplasty in painful chronic osteoporotic vertebral fractures. A report of 5 patients]. / Eficacia de la vertebroplastia en fracturas vertebrales crónicas sintomáticas debidas a osteoporosis. Estudio de 5 pacientes.

BACKGROUND AND OBJECTIVE: Percutaneous vertebroplasty (PVP) has been successfully used in the treatment of pain related to osteoporotic vertebral fractures refractory to medical therapy, especially in the treatment of acute factures. However, the effectiveness of this therapeutic approach in the treatment of painful chronic vertebral fractures is less clear. PATIENTS AND METHODS: In this report we evaluate the short and long-term effectiveness in pain relief of PVP in a group of 5 patients with pain related to chronic osteoporotic vertebral fractures without bone marrow edema (BME) on magnetic resonance imaging (MRI). All patients were followed during one year, assessing analgesic use, pain evolution (on a 10-point visual analog scale [VAS]), new vertebral fractures and other clinical complications. Seven procedures were performed in the 5 patients. RESULTS: All patients reported substantial improvement in back pain 2 weeks after the procedure, with a mean decrease of 53% in the VAS. However, one year after PVP most patients (4 out 5) worsened, achieving similar VAS scores to those obtained at baseline. No additional vertebral fractures or other clinical complications were observed. CONCLUSION: The present cases suggest that the long-term effectiveness of PVP in the treatment of painful chronic vertebral fractures without BME on MRI is scarce.

Effects of bilirubin and sera from jaundiced patients on osteoblasts: contribution to the development of osteoporosis in liver diseases.

UNLABELLED: Low bone formation is considered to be the main feature in osteoporosis associated with cholestatic and end-stage liver diseases, although the consequences of retained substances in chronic cholestasis on bone cells have scarcely been studied. Therefore, we analyzed the effects of bilirubin and serum from jaundiced patients on viability, differentiation, mineralization, and gene expression in the cells involved in bone formation. The experiments were performed in human primary osteoblasts and SAOS-2 human osteosarcoma cells. Unconjugated bilirubin or serum from jaundiced patients resulted in a dose-dependent decrease in osteoblast viability. Concentrations of bilirubin or jaundiced serum without effects on cell survival significantly diminished osteoblast differentiation. Mineralization was significantly reduced by exposure to 50 µM bilirubin at all time points (from -32% to -55%) and jaundiced sera resulted in a significant decrease on cell mineralization as well. Furthermore, bilirubin down-regulated RUNX2 (runt-related transcription factor 2) gene expression, a basic osteogenic factor involved in osteoblast differentiation, and serum from jaundiced patients significantly up-regulated the RANKL/OPG (receptor activator of nuclear factor-κB ligand/osteoprotegerin) gene expression ratio, a system closely involved in osteoblast-induced osteoclastogenesis. CONCLUSION: Besides decreased cell viability, unconjugated bilirubin and serum from jaundiced patients led to defective consequences on osteoblasts. Moreover, jaundiced serum up-regulates the system involved in osteoblast-induced osteoclastogenesis. These results support the deleterious consequences of increased bilirubin in advanced chronic cholestasis and in end-stage liver diseases, resulting in disturbed bone formation related to osteoblast dysfunction.

[Whipple's disease. Analysis of 6 cases]. / Enfermedad de Whipple. Estudio de 6 casos.

BACKGROUND AND OBJECTIVE: Whipple's disease (WD) is an infrequent multisystemic process, with a bacterial etiology and with a marked variability in relation to its clinical manifestations. The diagnosis is established by histopathologic study or by polymerase chain reaction (PCR) test. Our objective was to analyze the clinical characteristics and evolution of these patients. PATIENTS AND METHOD: We have reviewed the patients diagnosed with WD in our hospital during the last 20 years (1987-2007). RESULTS: We describe 6 patients with WD (5 men and one woman), with a mean age of 47 years. Most patients presented articular symptoms (n = 5), in 3 cases with intermittent rheumatism. The mean period of time previous to diagnosis was 59 months. All patients developed a chronic diarrheic syndrome, constitutional syndrome and polyadenopathies at the time of diagnosis. Laboratory studies showed increased erythrocyte sedimentation rate and C-reactive protein values, ferropenic microcytic anemia and low serum levels of cholesterol. The clinical diagnosis was confirmed by pathologic study in 5 patients, and by means of PCR study of spleen tissue in one patient. All patients were treated with cotrimoxazole for 2 years, with resolution of the symptoms. After a mean follow-up of 98 months, no recurrence of the symptoms has been observed in any case. CONCLUSIONS: Articular symptoms in the form of intermittent rheumatism are the most common form of presentation of WD. Diarrheic and constitutional syndrome, which are observed later in all patients, as well as the presence of adenopathies, oblige us to discard this process.