Cost-consequence analysis of tocilizumab versus adalimumab and etanercept among rheumatoid arthritis patients in Saudi Arabia: a single-center study.

BACKGROUND: The study aimed to examine the direct medical cost and impact of tocilizumab (TOZ) versus adalimumab (ADM) and etanercept (ETC) on reducing the levels of two inflammatory markers (e.g., C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) among patients with rheumatoid arthritis (RA) using real-world data from Saudi Arabia. METHOD: This was a single-center retrospective cohort study in which data for biologic-naïve RA patients aged ≥ 18 years and treated with TOZ, ADM, ETC were retrieved from the electronic medical records (EMRs) of a university-affiliated tertiary care center in Riyadh, Saudi Arabia. Patients were followed up at least one year after the treatment initiation. Bottom-up microcosting was utilized to estimate the direct medical costs. Additionally, inverse probability treatment weighting and bootstrapping with 10,000 replications were conducted to generate 95% confidence levels for costs and the mean reductions in CRP and ESR levels. RESULTS: The number of patients who met the inclusion criteria and were included in the analysis was 150 patients (TOZ (n = 56), ADM (n = 41), ETC (n = 53)). Patients on TOZ had 3.96 mg/L (95% CI: -0.229-4.95) and 11.21 mm/hr (95% CI: 10.28-18.11) higher mean reductions in the CRP and ESR levels compared to their counterparts on ADM, ETC, respectively. However, this was associated with mean annual incremental costs of USD 10,087.88 (95% CI: 9494.50-11,441.63) in all cost-effectiveness bootstrap distributions. CONCLUSION: Tocilizumab has shown better effectiveness in reducing the levels of CRP and ESR but with higher costs. Future studies should examine whether the reduction of these two inflammatory markers is associated with quality-adjusted life years (QALYs) gains.

Comparative effectiveness and cost evaluation of Risankizumab and Adalimumab in the management of psoriasis: a real-world study in Saudi Arabia.

BACKGROUND: Psoriasis, an immune-mediated chronic inflammatory disease primarily affecting skin and joints, has varying prevalence rates globally. It manifests in five types, with chronic plaque psoriasis being the most common. Treatment, which has no definitive cure, aims for complete resolution of skin symptoms and depends on disease extent, severity, and impact on patients' lives. Biologics are an emerging treatment for psoriasis, targeting specific inflammatory pathways for potentially safer, more effective outcomes. However, these come with significant costs, necessitating more research to ensure value for money. This study aimed to compare the effectiveness of Risankizumab versus Adalimumab, the most commonly utilized biologic for managing psoriasis in Saudi Arabia. METHODS: This study retrospectively compared the effectiveness and direct medical cost of Risankizumab and Adalimumab in treating chronic plaque psoriasis in adults from two Saudi Arabian healthcare centers. The Psoriasis Area and Severity Index (PASI) and body surface area (BSA) were used to assess treatment effectiveness, with patient data sourced from electronic medical records. Multiple regression analysis was performed to examine various factors affecting treatment outcomes. An economic evaluation was conducted to examine the cost-effectiveness of the two drugs, considering four scenarios with varying dosage patterns and costs. Analysis was performed from the perspective of public healthcare payers and considered all utilized health services. RESULTS: The data for 70 patients were analyzed, with comparable baseline characteristics between groups. While Risankizumab led to a greater reduction in PASI scores and BSA affected, these results were not statistically significant. The annual treatment cost for Risankizumab was higher than Adalimumab. Various scenarios were studied, considering real acquisition costs, double dosing for Adalimumab, and the use of biosimilars. A scenario assuming double dosing for Adalimumab and a 40% discount for Risankizumab demonstrated both cost and efficacy advantages in 71.25% of cases. CONCLUSIONS: This study compared the effectiveness and cost of Risankizumab and Adalimumab for treating chronic plaque psoriasis in Saudi Arabian hospitals. Although Risankizumab showed a greater reduction in symptoms, the difference was not statistically significant. However, under certain scenarios, Risankizumab demonstrated cost and efficacy advantages. These findings may influence treatment decisions for psoriasis, but further research is needed.

Clinical and economic evaluations of natalizumab, rituximab, and ocrelizumab for the management of relapsing-remitting multiple sclerosis in Saudi Arabia.

INTRODUCTION: The advent of new disease-modifying therapies (DMTs), such as monoclonal antibodies (mAbs), resulted in significant changes in the treatment guidelines for Multiple sclerosis (MS) and improvement in the clinical outcomes. However, mAbs, such as rituximab, natalizumab, and ocrelizumab, are expensive with variable effectiveness rates. Thus, the present study aimed to compare the direct medical cost and consequences (e.g., clinical relapse, disability progression, and new MRI lesions) between rituximab and natalizumab in managing relapsing-remitting multiple sclerosis (RRMS) in Saudi Arabia. Also, the study aimed to explore the cost and consequence of ocrelizumab in managing RRMS as a second-choice treatment. METHODS: The electronic medical records (EMRs) of patients with RRMS were retrospectively reviewed to retrieve the patients' baseline characteristics and disease progression from two tertiary care centers in Riyadh, Saudi Arabia. Biologic-naïve patients treated with rituximab or natalizumab or those switched to ocrelizumab and treated for at least six months were included in the study. The effectiveness rate was defined as no evidence of disease activity (NEDA-3) (i.e., absence of new T2 or T1 gadolinium (Gd) lesions as demonstrated by the Magnetic Resonance Imaging (MRI), disability progression, and clinical relapses), while the direct medical costs were estimated based on the utilization of healthcare resources. In addition, bootstrapping with 10,000 replications and inverse probability weighting based on propensity score were conducted. RESULTS: Ninety-three patients met the inclusion criteria and were included in the analysis (natalizumab (n = 50), rituximab (n = 26), ocrelizumab (n = 17)). Most of the patients were otherwise healthy (81.72%), under 35 years of age (76.34%), females (61.29%), and on the same mAb for more than one year (83.87%). The mean effectiveness rates for natalizumab, rituximab, and ocrelizumab were 72.00%, 76.92%, and 58.83%, respectively. Natalizumab mean incremental cost compared to rituximab was $35,383 (95% CI: $25,401.09- $49,717.92), and its mean effectiveness rate was 4.92% lower than rituximab (95% CI: -30-27.5) with 59.41% confidence level that rituximab will be dominant. CONCLUSIONS: Rituximab seems to be more effective and is less costly than natalizumab in the management of RRMS. Ocrelizumab does not seem to slow the rates of disease progression among patients previously treated with natalizumab.

Cost effectiveness of rivaroxaban versus warfarin among nonvalvular atrial fibrillation patients in Saudi Arabia: A Single-Center retrospective cohort study.

Background: Rivaroxaban is a novel oral anticoagulant (NOAC) that is commonly used for stroke prevention among patients with atrial fibrillation (AF). However, its cost effectiveness in reducing the risk of hospitalization and mortality in comparison to warfarin among nonvalvular AF patients in Saudi Arabia is largely unknown. Methods: This was a single-center retrospective chart review of adult patients (≥18 years) with nonvalvular AF who were treated with warfarin or rivaroxaban for at least 12 months. Patients with mitral valve stenosis were excluded from the study. Multiple logistic regression was conducted to examine the risk of hospitalization and mortality as a composite outcome, and all annual healthcare costs were captured. Inverse probability treatment weighting with bootstrapping was conducted to determine the mean costs and effectiveness rates. Results: Two-hundred and twenty-six patients (142 on rivaroxaban and 84 on warfarin) met the inclusion criteria and were included in the analysis. Most of the patients were females (65.91 %), had diabetes (50.57 %) and hypertension (73.76 %), and with a mean age of 68.95 ± 12.55 years. No significant difference in the odds of the composite outcome for rivaroxaban versus warfarin was found (OR = 0.785, 95 % CI = [0.427-1.446], p = 0.443). Rivaroxaban resulted in a mean annual cost saving of $13,260.79 with an 87.65 % confidence level that it would be more effective than warfarin with a mean difference in effectiveness rate of 0.168 % (95 % CI [-5.210-18.36]). Conclusion: Rivaroxaban was associated with lower direct medical costs and non-inferior effectiveness among nonvalvular AF patients in comparison to warfarin.

The impact of Hydroxyurea on the rates of Vaso-occlusive crises in patients with sickle cell disease in Saudi Arabia: a single-center study.

BACKGROUND: Vaso-occlusive crises (VOCs) are acute and common painful complication of sickle cell disease (SCD), and are the main reason behind the frequent emergency department visits among SCD patients. Hydroxyurea (HU) is an old and commonly used medication that demonstrated its effectiveness in reducing the risk of VOCs and the incidence of hospitalization. Although multiple studies have examined the impact of HU on the rates of VOCs, few have explored its effectiveness among SCD patients in Saudi Arabia. METHODS: This was a single-center retrospective cohort study in which the electronic medical records of patients with SCD who have not had any previous exposure to HU prior to the initiation of HU treatment for ≥12 months were recruited. Paired t-test was conducted to examine the difference in the rates of VOCs, and levels of hemoglobin (Hgb), hematocrit (HCT), and platelet counts (PLT Ct) prior to the initiation of HU therapy and 12 months later. Multiple linear regression was conducted to examine whether age, gender, use of opioid analgesics, Hgb, HCT, and PLT Ct levels predict higher or lower rates of VOCs. RESULTS: One hundred and fifty-six patients met the inclusion criteria and were included in the analysis. About 51% of the patients were males, and their mean age was 12.69 years. The mean HU dosage was 16.52 mg/kg/day, and the mean reduction in the rate of VOCs was 1.36 events per patient per year (95% CI [1.03-1.70], p < 0.0001) after the initiation of HU. Females were more likely to have greater reduction in the rates of VOCs in comparison to their male counterparts (ß-estimate = 12.85, 95% CI [0.759-24.93], p = 0.0374). CONCLUSION: The use of HU results in a significant reduction in the rates of VOCs and emergency department visits. Future studies with robust research designs should be conducted to further examine the impact of HU on VOCs, hospitalization, and length of stay as well as compare HU to other newly approved medications for SCD, such as crizanlizumab.

Alleviation of cisplatin-induced neuropathic pain, neuronal apoptosis, and systemic inflammation in mice by rapamycin.

Platinum-based chemotherapeutic treatment of cancer patients is associated with debilitating adverse effects. Several adverse effects have been well investigated, and can be managed satisfactorily, but chemotherapy-induced peripheral neuropathy (CIPN) remains poorly treated. Our primary aim in this study was to investigate the neuroprotective effect of the immunomodulatory drug rapamycin in the mitigation of cisplatin-induced neurotoxicity. Pain assays were performed in vivo to determine whether rapamycin would prevent or significantly decrease cisplatin-induced neurotoxicity in adult male Balb/c mice. Neuropathic pain induced by both chronic and acute exposure to cisplatin was measured by hot plate assay, cold plate assay, tail-flick test, and plantar test. Rapamycin co-treatment resulted in significant reduction in cisplatin-induced nociceptive-like symptoms. To understand the underlying mechanisms behind rapamycin-mediated neuroprotection, we investigated its effect on certain inflammatory mediators implicated in the propagation of chemotherapy-induced neurotoxicity. Interestingly, cisplatin was found to significantly increase peripheral IL-17A expression and CD8- T cells, which were remarkably reversed by the pre-treatment of mice with rapamycin. In addition, rapamycin reduced the cisplatin-induced neuronal apoptosis marked by decreased neuronal caspase-3 activity. The rapamycin neuroprotective effect was also associated with reversal of the changes in protein expression of p21Cip1, p53, and PUMA. Collectively, rapamycin alleviated some features of cisplatin-induced neurotoxicity in mice and can be further investigated for the treatment of cisplatin-induced peripheral neuropathy.

Real-World Comparative Cost-Effectiveness Analysis of Different Classes of Disease-Modifying Therapies for Relapsing-Remitting Multiple Sclerosis in Saudi Arabia.

The very fact that multiple sclerosis (MS) is incurable and necessitates life-long care makes it one of the most burdensome illnesses. The aim of this study was to compare the cost-effectiveness of orally administered medications (e.g., fingolimod, dimethyl fumarate, and teriflunomide), interferon (IFN)-based therapy, and monoclonal antibodies (MABs) (e.g., natalizumab and rituximab) in the management of relapsing-remitting multiple sclerosis (RRMS) in Saudi Arabia using real-world data. This was a retrospective cohort study in which patients with RRMS aged ≥18 years without any other chronic health conditions with non-missing data for at least 12 months were recruited from the electronic health records of a university-affiliated tertiary care center. Multiple logistic regressions controlling for age, sex, and duration of therapy were conducted to examine the odds of disability progression, clinical relapse, MRI lesions, and composite outcome (e.g., relapse, lesion development on MRI, disability progression). The number of patients who met the inclusion criteria and were included in the analysis was 146. Most of the patients were female (70.51%) and young (e.g., ≤35 years of age). There were 40 patients on the orally administered agents (e.g., dimethyl fumarate, teriflunomide, fingolimod), 66 patients were on IFN-based therapy (e.g., Rebif®), and 40 patients were on monoclonal antibodies (e.g., rituximab and natalizumab). Patients on MABs had lower odds of the composite outcome (OR = 0.17 (95% CI: 0.068-0.428)). The use of orally administered agents was dominant (e.g., more effective and less costly), with average annual cost savings of USD -4336.65 (95% CI: -5207.89--3903.32) and 8.11% higher rate of effectiveness (95% CI: -14.81-18.07) when compared with Rebif®. With regard to the use of MABs in comparison to Rebif®, MABs were associated with higher cost but a better rate of effectiveness, with an average additional annual cost of USD 1381.54 (95% CI: 421.31-3621.06) and 43.11% higher rate of effectiveness (95% CI: 30.38-61.15) when compared with Rebif®. In addition, the use of MABs was associated with higher cost but a better rate of effectiveness, with an average additional annual cost of USD 5717.88 (95% CI: 4970.75-8272.66) and 35% higher rate of effectiveness (95% CI: 10.0-42.50) when compared with orally administered agents. The use of MABs in the management of RRMS among the young patient population has shown to be the most effective therapy in comparison to both IFN-based therapy (e.g., Rebif®) and orally administered agents, but with higher cost. Orally administered agents resulted in better outcomes and lower costs in comparison to IFN-based therapy. Future studies should further examine the cost-effectiveness of different disease-modifying therapies for the management of RRMS using more robust study designs.

Predictors of Opioid Prescription Among a Sample of Patients with Acute Musculoskeletal Pain at a Tertiary Care Hospital in Saudi Arabia.

BACKGROUND: Musculoskeletal pain is one of the most complex and debilitating types of pain. Although different pharmacologic treatments are available, very few studies have explored the predictors for opioid analgesics prescription to manage this type of pain. OBJECTIVE: The aim of this study was to explore the predictors for opioid prescription in patients with acute musculoskeletal pain in Saudi Arabia. METHODS: This was a single-center, retrospective chart review of adult patients (≥18 yrs.) with an acute nociceptive musculoskeletal pain at a university-affiliated medical center in Riyadh, Saudi Arabia. Cancer patients and those with chronic neuropathic pain were excluded. Patients' age, gender, number of comorbidities, duration of pain management, number of clinic visits for pain, and Numeric Pain Rating Scale (NPRS) scores at rest and with normal activities were collected. Multiple logistic regression was conducted to examine the relationship between the type of musculoskeletal pain and the prescription of opioid analgesics controlling for NPRS score on activity, age, gender, number of comorbidities, duration of pain treatment, and number of clinic visits for pain. RESULTS: The mean age of the 227 patients, who met the inclusion criteria, was 39 years and 68% of them were male. Sixty-three percent of the patients were prescribed opioid analgesics, and 61% of them had shoulder pain, 29% had back pain, and 10% had lower extremity pain (eg, hip, thigh, lower leg, knee, ankle, and foot pain). Tramadol was the most commonly prescribed opioid analgesic (82%), followed by codeine (13%). Ninety-seven percent of patients who were prescribed non-opioid analgesics had shoulder pain. Patients with shoulder pain had lower odds of receiving opioid analgesics (OR=0.019, P<0.0001, 95% CI=0.004-0.081) in comparison to their counterparts who had lower extremity or back pains. Moreover, the higher the pain score on activity was, the higher odds of receiving opioid analgesics (OR=1.317, P<0.0001, 95% CI=1.029-1.685). CONCLUSION: Future studies should explore the impact of different opioid prescribing policies to improve the quality of patient care and reduce the unnecessary prescribing of opioids for patients with non-cancer musculoskeletal pain.

Drug-drug interactions and pharmacists' interventions among psychiatric patients in outpatient clinics of a teaching hospital in Saudi Arabia.

BACKGROUND: Lack of recognition of labeled drug-drug interactions (DDIs) is a type of medication error of particular relevance to the treatment of psychiatric patients. Pharmacists are in a position to detect and address potential DDIs. OBJECTIVE: This study aimed to explore pharmacists' role in the identification and management of DDIs among psychiatric patients in psychiatric outpatient clinics of a university-affiliated tertiary care hospital in Riyadh, Saudi Arabia. METHOD: This study was a retrospective, cross-sectional medical chart review of patients visiting outpatient psychiatric clinics. It utilized medical records of patients who were taking any psychotropic medications and were prescribed at least one additional drug. The hospital Computerized Physician Order Entry system was used to identify DDIs and determine the pharmacists' interventions. The Beers criteria were applied to detect inappropriate prescribing among older patients. RESULTS: On average, the pharmacists intervened in 12 out of 213 (5.6%) cases of major or moderate DDIs. Older age, higher number of prescription medications, the severity of DDIs, and the utilization of lithium and anticoagulants were positively associated with the pharmacist undertaking an action. CONCLUSION: Future studies should explore the prevalence rate of harmful DDIs among psychiatric patients on a large scale and examine the effectiveness of different pharmacy policies in the detection and management of DDIs.