Assessment of Tocilizumab (Humanized Monoclonal Antibody) for Therapeutic Efficacy and Clinical Safety in Patients with Coronavirus Disease (COVID-19).

Background and objectives: COVID-19 patients exhibit a broad range of manifestations, presenting with a flu-like respiratory tract infection that can advance to a systemic and severe disease characterized by pneumonia, pulmonary edema, severe damage to the airways, and acute respiratory distress syndrome (ARDS, causing fatality in 70% of COVID-19 cases). A 'cytokine storm' profile is found in most severely influenced COVID-19 patients. The treatment protocol of the disease also includes tocilizumab, which is a humanized monoclonal antibody used to treat autoimmune and inflammatory conditions. This study was designed (1) to assess the role of tocilizumab in COVID-19 patients regarding therapeutic efficacy through evaluation of cytokine release syndrome (CRS) resolution and anticoagulant effect, analyzing clinical safety via monitoring of associated adverse effects profile; and (2) to compare the clinical safety and therapeutic efficacy of institutional treatment regimen (alone) versus tocilizumab added to an institutional treatment module in COVID-19 patients. Materials and Methods: In this study, the endpoints parametric assessment of severely diseased patients of COVID-19 was performed (total n = 172, control group (institutional protocol treatment provided), n = 101 and test group (tocilizumab provided), n = 71) at the Khyber Teaching Institution, MTI, Peshawar. The assessments were compared using non-parametric analyses at baseline and after a follow-up of 12−18 days until the patient discharged or expired. Results: Results of the study revealed an insignificant difference among the control vs. test group in resolving inflammatory parameters (C-reactive protein (CRP) 21.30 vs. 50.07; p = 0.470, ferritin 482.9 vs. 211.5; p = 0.612, lactate dehydrogenase (LDH) 29.12 vs.18.8; p = 0.0863, and D-dimer 464 vs.164.4; p = 0.131). However, a statistically significant difference was found between the control group and test group regarding coagulation parameters (international normalized ratio (INR) 0.12 vs. −0.07; p ≤ 0.001; activated partial thromboplastin time (aPTT) 0.42 vs. −1.16; p ≤ 0.001; prothrombin time (PT) 0.31 vs. −0.96; p ≤ 0.001; platelet count −12.34 vs. −1.47; p = 0.012) and clinical survival rate (89.10 vs. 90.14; p < 0.001). Furthermore, there was significantly higher infection rates and raised alanine aminotransferase (ALT) and alkaline phosphatase (ALP) associated with the tocilizumab group as compared to those receiving institutional treatment (bacterial infections: 0.99% vs. 15.49%; p ≤ 0.01, ALT: 3.96% vs. 28.16%; p ≤ 0.01, ALP: 1.98% vs. 22.53%; p ≤ 0.01). Conclusions: From this study, it was concluded that tocilizumab can be a better drug of choice in terms of efficacy, particularly in resolving coagulopathy in severe COVID-19 patients.

Assessment of Contributing Factors and Treatment Practices for Therapeutic Efficacy and Drug-Related Problems in Suicidal Psychotic Patients.

Suicide, a deliberate act of self-harm with the intention to die, is an emerging health concern but, unfortunately, the most under-researched subject in Pakistan, especially in Khyber Pukhtunkhwa (KPK). In this study, we aimed to identify risk factors that can be associated with suicidal behavior (SB) and to evaluate the prevailing treatment practices for therapeutic efficacy and drug-related problems (DRPs) in psychotic patients among the local population of KPK. A prospective, multicenter study was conducted for suicidal cases admitted to the study centers by randomized sampling. Socio-demographics and data on suicidal behavior were assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS), socioeconomic condition by Kuppuswamy socioeconomic scale (KSES) and treatment adherence by Morisky Medication-Taking Adherence Scale (MMAS-4). Drug-related problems and the therapeutic efficacy of prevailing treatment practices were assessed at baseline and follow-up after 3 months of treatment provided. Regarding suicidality (N = 128), females reported more ideations (63.1%), while males witnessed more suicidal behavior (66.6%, p < 0.001). Suicide attempters were mostly married (55.6%, p < 0.002); highly educated (53.9%, p = 0.004); dissatisfied with their life and had a previous history (p < 0.5) of suicide attempt (SA) (20.6%), self-injurious behavior (SIB) (39.7%) and interrupted (IA) or aborted attempts (AA) (22.2%). A greater improvement was observed in patients receiving combination therapy (p = 0.001) than pharmacotherapy (p = 0.006) or psychotherapy (p = 0.183), alone. DRPs were also detected, including drug-selection problems (17.88%), dose-related problems (20.64%), potential drug−drug interactions (24.31%), adverse drug reactions (11.46%) and other problems like inadequate education and counseling (21.55%). Furthermore, it was also found that psychotic patients with suicidal ideations (SI) were significantly (p = 0.01) more adherent to the treatment as compared to those with suicidal attempts. We concluded that suicide attempters differed significantly from patients with suicidal ideations in psychotic patients and presented with peculiar characteristics regarding socio-demographic factors. A combination of therapies and adherence to the treatment provided better outcomes, and targeted interventions are warranted to address drug-related problems.