Multiple infliximab biosimilar switches appear to be safe and effective in a real-world inflammatory bowel disease cohort.

BACKGROUND: Switching from originator infliximab (IFX) to biosimilar IFX is effective and safe. However, data on multiple switching are scarce. The Edinburgh inflammatory bowel disease (IBD) unit has undertaken three switch programmes: (1) Remicade to CT-P13 (2016), (2) CT-P13 to SB2 (2020), and (3) SB2 to CT-P13 (2021). OBJECTIVE: The primary endpoint of this study was to assess CT-P13 persistence following switch from SB2. Secondary endpoints included persistence stratified by the number of biosimilar switches (single, double and triple), effectiveness and safety. METHODS: We performed a prospective, observational, cohort study. All adult IBD patients on IFX biosimilar SB2 underwent an elective switch to CT-P13. Patients were reviewed in a virtual biologic clinic with protocol driven collection of clinical disease activity, C-reactive protein (CRP), faecal calprotectin (FC), IFX trough/antibody levels, and drug survival. RESULTS: 297 patients (CD n = 196 [66%], ulcerative colitis/inflammatory bowel disease unclassified n = 101, [34%]) were switched (followed-up: 7.5 months [6.8-8.1]). This was the third, second and first IFX switch for 67/297 (22.5%), 138/297 (46.5%) and 92/297 (31%) of the cohort respectively. 90.6% of patients remained on IFX during follow-up. The number of switches was not independently associated with IFX persistence after adjusting for confounders. Clinical (p = 0.77), biochemical (CRP ≤5 mg/ml; p = 0.75) and faecal biomarker (FC<250 µg/g; p = 0.63) remission were comparable at baseline, week 12 and week 24. CONCLUSION: Multiple successive switches from IFX originator to biosimilars are effective and safe in patients with IBD, irrespective of the number of IFX switches.

Longstanding Phenytoin Use as a Cause of Progressive Dyspnea.

CASE PRESENTATION: A 54-year-old South African man with a medical history of type 2 diabetes mellitus, seizure disorder, OSA, and latent TB presented to the ER with gradually progressive dyspnea over months. He also reported occasional dry cough and fatigue at presentation but denied fever, chills, chest pain, leg swelling, palpitations, or lightheadedness. He was treated with a course of levofloxacin for presumed community-acquired pneumonia as an outpatient without improvement and had tested negative for COVID-19. He denied occupational or environmental exposures or sick contacts, though he had traveled back to South Africa 1 year before presentation. He had complex partial seizures for the past 22 years, which had been well controlled on phenytoin (300 mg daily). His other home medications included dulaglutide, sertraline, and atorvastatin and had no recent changes. He quit smoking 30 years ago after smoking one pack per day for 10 years.

OpenSAFELY: impact of national guidance on switching anticoagulant therapy during COVID-19 pandemic.

BACKGROUND: Early in the COVID-19 pandemic, the National Health Service (NHS) recommended that appropriate patients anticoagulated with warfarin should be switched to direct-acting oral anticoagulants (DOACs), requiring less frequent blood testing. Subsequently, a national safety alert was issued regarding patients being inappropriately coprescribed two anticoagulants following a medication change and associated monitoring. OBJECTIVE: To describe which people were switched from warfarin to DOACs; identify potentially unsafe coprescribing of anticoagulants; and assess whether abnormal clotting results have become more frequent during the pandemic. METHODS: With the approval of NHS England, we conducted a cohort study using routine clinical data from 24 million NHS patients in England. RESULTS: 20 000 of 164 000 warfarin patients (12.2%) switched to DOACs between March and May 2020, most commonly to edoxaban and apixaban. Factors associated with switching included: older age, recent renal function test, higher number of recent INR tests recorded, atrial fibrillation diagnosis and care home residency. There was a sharp rise in coprescribing of warfarin and DOACs from typically 50-100 per month to 246 in April 2020, 0.06% of all people receiving a DOAC or warfarin. International normalised ratio (INR) testing fell by 14% to 506.8 patients tested per 1000 warfarin patients each month. We observed a very small increase in elevated INRs (n=470) during April compared with January (n=420). CONCLUSIONS: Increased switching of anticoagulants from warfarin to DOACs was observed at the outset of the COVID-19 pandemic in England following national guidance. There was a small but substantial number of people coprescribed warfarin and DOACs during this period. Despite a national safety alert on the issue, a widespread rise in elevated INR test results was not found. Primary care has responded rapidly to changes in patient care during the COVID-19 pandemic.

A multicenter survey on the aspects of everyday life in adult patients with primary antibody deficiencies treated with immunoglobulin G replacement during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has changed many aspects of everyday life. Patients with primary immunodeficiency (PID) are in a particularly difficult situation. The purpose of the present study was to contribute to the very limited research on the everyday aspects of functioning in PID patients during the COVID-19 pandemic. METHODS: The survey included 85 adult PID patients treated with immunoglobulin replacement therapy in four reference centers for immunology. Everyday functioning of the patients as well as their opinion concerning new solutions in medical care were analyzed. RESULTS: During the pandemic, the percentage of patients experiencing fear/anxiety has increased from 47% to 70%. The wide dissemination of information about the SARS-CoV-2 in the media has increased anxiety in 40% of the patients. Patients diagnosed with PID were most afraid of the exposure to contact with strangers, especially in public places. As many as 67 respondents (79%) considered the introduction of restrictions concerning social functioning as good. Only every fifth person learned about the pandemic from reliable sources. Eighty three percent of the patients receiving immunoglobulin substitution experienced less fear of SARS-CoV-2 infection. The patients positively evaluated the solutions related to the direct delivery of drugs to the place of residence in order to continue home IgRT therapy. Fifty three respondents (62.5%) believed that the possibility of a remote consultation was a very good solution. CONCLUSION: It is necessary to increase educational activities concerning the pandemic provided by health care professionals, as patients obtain information mainly from the media and the Internet, which adversely affects the feeling of anxiety. The pandemic, in addition to the very negative impact on patients and the deterioration of their daily functioning, has made patients appreciate their life more, devote more time to family and friends, and do things they like.

Switch to subcutaneous infliximab during the SARS-CoV-2 pandemic: preliminary results.

A new subcutaneous formulation of the infliximab biosimilar CT-P13 has recently been developed for the treatment of inflammatory bowel disease (IBD), providing response rates similar to intravenous treatment. The use of this new formulation was requested, in an effort to limit patient attendance at intravenous infusion centers and to maintain biological treatment during the COVID-19 pandemic. The objective of this observational, retrospective and descriptive study was to assess CT-P13 efficacy and safety after switching from intravenous to a subcutaneous formulation in patients with IBD receiving maintenance therapy. This article shows preliminary results after six months of follow-up.

Changes in Disease-Modifying Antirheumatic Drug Treatment for Patients With Rheumatoid Arthritis in the US During the COVID-19 Pandemic: A Three-Month Observational Study.

OBJECTIVE: To understand medication, lifestyle, and clinical care changes of persons with rheumatoid arthritis (RA) during the first months (March 2020 through May 2020) of the COVID-19 pandemic in the US. METHODS: Data were collected from adults with RA participating in FORWARD, The National Databank for Rheumatic Diseases observational registry, who answered COVID-19 web-based surveys in May 2020 and previously provided baseline characteristics and medication use prior to the US COVID-19 pandemic. We compared medication changes by disease-modifying antirheumatic drug (DMARD) exposure in logistic models that were adjusted for age, sex, comorbidities including pulmonary and cardiovascular diseases, education level, health insurance status, RA disease activity, fatigue, and polysymptomatic distress. RESULTS: Of 734 respondents, 221 (30%) reported medication changes. Among respondents who experienced a medication change, i.e., "medication changers/changers," glucocorticoids (GCs) were more commonly used compared to respondents who did not experience a medication change ("non-changers") (33% versus 18%). Non-hydroxychloroquine conventional DMARDs were less commonly used in changers compared to non-changers pre-COVID-19 (49% versus 62%), and changers reported more economic hardship during the COVID-19 pandemic compared to non-changers (23% versus 15%). While JAK inhibitor use was associated with the likelihood of a medication change, with an odds ratio (OR) of 1.9 (95% confidence interval [95% CI] 1.0, 3.4), only pre-COVID GC use remained a strong predictor for medication change in multivariable models (OR 3.0 [95% CI 1.9, 4.9]). Change in care was observed to have a significant association with pulmonary disease (OR 2.9 [95% CI 1.3, 6.5]), worse RA disease activity (OR 1.1 [95% CI 1.0, 1.1]), and GC use (OR 1.6 [95% CI 1.0, 2.5]). While the incidence of medication changes was the same before and after the American College of Rheumatology (ACR) guidance for the management of rheumatic disease in adult patients during the COVID-19 pandemic were first published in April 2020, self-imposed changes in medication were approximately twice as likely before publication of the guidelines, and physician-guided changes were more likely after publication. CONCLUSION: Persons with RA in the US made substantial medication changes during the first three months of the COVID-19 pandemic, and changes among persons with RA after publication of the ACR guidance in April 2020 were made with increased physician guidance.

When Manual Analysis of 12-Lead ECG Holter Plays a Critical Role in Discovering Unknown Patterns of Increased Arrhythmogenic Risk: A Case Report of a Patient Treated with Tamoxifen and Subsequent Pneumonia in COVID-19.

Several medicines, including cancer therapies, are known to alter the electrophysiological function of ventricular myocytes resulting in abnormal prolongation and dispersion of ventricular repolarization (quantified by multi-lead QTc measurement). This effect could be amplified by other concomitant factors (e.g., combination with other drugs affecting the QT, and/or electrolyte abnormalities, such as especially hypokalemia, hypomagnesaemia, and hypocalcemia). Usually, this condition results in higher risk of torsade de point and other life-threatening arrhythmias, related to unrecognized unpaired cardiac ventricular repolarization reserve (VRR). Being VRR a dynamic phenomenon, QT prolongation might often not be identified during the 10-s standard 12-lead ECG recording at rest, leaving the patient at increased risk for life-threatening event. We report the case of a 49-year woman, undergoing tamoxifen therapy for breast cancer, which alteration of ventricular repolarization reserve, persisting also after correction of concomitant recurrent hypokalemia, was evidenced only after manual measurements of the corrected QT (QTc) interval from selected intervals of the 12-lead ECG Holter monitoring. This otherwise missed finding was fundamental to drive the discontinuation of tamoxifen, shifting to another "safer" therapeutic option, and to avoid the use of potentially arrhythmogenic antibiotics when treating a bilateral pneumonia in recent COVID-19.

Outpatient management of chronic warfarin therapy at a pharmacist-run anticoagulation clinic during the COVID-19 pandemic.

As a result of infection control regulations during the coronavirus disease 2019 (COVID-19) pandemic, anticoagulation clinics have been required to adjust their practices in order to continue providing safe and effective services for their patients. In accordance with a guidance document issued by the Anticoagulation Forum, The Brooklyn Hospital Center (TBHC) anticoagulation clinic in Brooklyn, New York implemented measures including telemedicine follow-ups instead of in-person clinic visits, extending the interval of INR testing, and reviewing eligible candidates for transition from warfarin to direct oral anticoagulants. This study describes the outcomes of one hospital-based clinic location in the 3 months before and after COVID-19 became a significant concern in the New York City area. The primary outcome of time-in-therapeutic range (TTR) for patients receiving warfarin was 60.6 % and 65.8 % in the pre-COVID and post-COVID groups, respectively (p = 0.21). For secondary outcomes, there was no difference in percent of therapeutic INRs (51.5 % pre-COVID v. 44.8 % post-COVID, p = 0.75) or percent of INRs ≥ 4.5 (2.3 % pre-COVID v. 4 % post-COVID, p = 0.27). Based on the data reported in this study, the short-term changes implemented at TBHC's anticoagulation clinic did not appear to cause reductions in safety and efficacy of chronic warfarin therapy management.

Change in glucose-lowering medication regimens in individuals with type 2 diabetes mellitus during the COVID-19 pandemic in Germany.

AIM: To estimate the proportion of individuals with type 2 diabetes mellitus (T2DM) undergoing changes in glucose-lowering therapy in 2019 and 2020. METHOD: Individuals with T2DM who had at least one consultation in one of 940 general (including diabetologist) practices in Germany between January and July 2019 (N = 79 268) and between January and July 2020 (N = 85 046) were included. Therapy changes were defined as the prescription of new glucose-lowering drugs, with or without the discontinuation of previous treatments (therapy switch and add-on therapy, respectively). The number of T2DM patients with at least one medication regimen change was calculated for the periods 1 January to 14 March in 2019 and 2020, and for the periods 15 March to 31 July in 2019 and 2020. March 2020 corresponded to the beginning of the lockdown in Germany. RESULTS: Overall, there was a decrease in the number of patients with at least one medication regimen change in the period 15 March to 31 July 2019 compared with 15 March to 31 July 2020 (dipeptidyl peptidase-4 inhibitors: -15%; sodium-glucose co-transporter-2 inhibitors: -3%; glucagon-like peptide-1 receptor agonists: 0%; other oral glucose-lowering drugs: -6%; and insulin: -21%). CONCLUSIONS: The coronavirus disease-2019 (COVID-2019) pandemic had a strong impact on glucose-lowering drug use in T2DM patients in Germany. More research is warranted to further investigate the treatment and management of T2DM individuals during the COVID-19 era in Germany and elsewhere.

Management of patients with Behçet's disease during the COVID-19 pandemic.

Behçet's disease is a disease characterized by chronic inflammatory vasculitis. In the clinical symptoms of Behçet's disease, many immunosuppressive and immunomodulatory drugs are used. The suspicion that drugs used in chronic disease treatments such as Behçet's disease during pandemic will increase the risk of transmission of COVID-19 disease, and that the disease may progress more lethally in these patients after the infection caused clinicians to worry. As far as we know, there is no study in the literature about the management of patients with Behçet's disease in the pandemic period. Fifty-four patients with Behçet's disease who were admitted to the dermatology outpatient clinic between 11 March and July 14, 2020 were retrospectively analyzed. In this pandemic period, 44 of 54 patients were recommended to continue their previous treatment. While the dose of medication used by 7 patients was reduced, it was decided to change the treatment of 3 patients. No life-threatening activation was observed. None of the patients developed COVID-19 disease. This article is important in terms of being the first study in the literature examining the treatment of patients with Behçet's disease during the COVID-19. In this period, we know that the treatment practices in chronic diseases change frequently daily, and in this respect, we hope that our study will provide a perspective to other dermatology clinics in terms of the treatment of Behçet's disease during the pandemic.

Clarithromycin use for adjunct surgical prophylaxis before non-elective cesarean deliveries to adapt to azithromycin shortages in COVID-19 pandemic.

OBJECTIVE: This study aimed to evaluate safety and effectiveness of clarithromycin as adjunctive antibiotic prophylaxis for patients undergoing non-elective cesarean delivery in comparison with no macrolides, to adapt to azithromycin shortages in COVID-19 pandemic. STUDY DESIGN: We conducted a multi-center, prospective observational cohort study from March 23, 2020 through June 1, 2020. We followed all women receiving either clarithromycin or no macrolide antibiotic for adjunct surgical prophylaxis for non-elective cesarean deliveries. The primary outcome was development of postpartum endometritis. Secondary outcomes included meconium-stained amniotic fluid at time of cesarean delivery, neonatal sepsis, neonatal intensive care unit admission, and neonatal acute respiratory distress syndrome. All patients in this study were tested for SARS-CoV-2 infection and resulted negative. RESULTS: This study included 240 patients, with 133 patients receiving clarithromycin and 107 patients receiving no adjunct macrolide prophylaxis. Patients receiving clarithromycin were noted to have significantly lower rates of postpartum endometritis as compared to those who did not receive adjunct prophylaxis (4.5% versus 11.2%, p = 0.025). In crude (unadjusted) analysis, a significantly lower risk of developing endometritis was noted in the clarithromycin group as compared to the control group (66% decreased risk, 95% CI 0.12 to 0.95, p = 0.040). When adjusted for perceived confounders, a significant difference was again noted (67% decreased risk, 95% CI 0.11 to 0.97, p = 0.034). Stratified analysis of significantly different demographic factors including Black race, BMI, and age was performed. A significantly decreased risk of development of endometritis when taking clarithromycin versus no adjunct macrolide was noted for Black race women in crude and adjusted models (crude: 87% decreased risk, 95% CI 0.08 to 0.83, p = 0.032; adjusted: 91% decreased risk, 95% CI 0.06 to 0.79, p = 0.026). This was also noted for women aged 18-29 years in crude and adjusted models (crude: model, 79% decreased risk, 95% CI 0.06 to 0.80, p = 0.014; adjusted model: 75% decreased risk, 95% CI 0.06 to 0.94, p = 0.028). All other stratified analyses did not yield significant differences in endometritis risk. CONCLUSION: Our study suggests that administration of clarithromycin for adjunctive surgical prophylaxis for non-elective cesarean deliveries may be a safe option that may provide suitable endometritis prophylaxis in cases where azithromycin is unavailable, as was the case during the start of COVID-19 pandemic, most especially for Black race women and women ages 18-29 years.

Transitioning From Immunosuppressants to Dupilumab in Pediatric Atopic Dermatitis.

Dupilumab has recently been approved by the Food and Drug Administration for use for treatment of moderate to severe atopic dermatitis in children aged 6 to 11 years. It presents a novel treatment option with a favorable safety profile for patients who are currently reliant on immunosuppressants, including cyclosporine A, methotrexate, and mycophenolate mofetil. Particularly during the current COVID-19 pandemic, immunosuppression should be avoided to retain intrinsic antiviral immunity. Transitioning to dupilumab should be executed strategically-tapering immunosuppressants and minimizing risk of flare by overlapping with the biologic. Herein, we use results of outcome measurements from LIBERTY AD ADOL and LIBERTY AD PEDS trials of dupilumab in adolescents aged 12 to 18 years and children aged 6 to 11 years, respectively, to propose a schematic for an 8-week transition between medications.

COVID-19 and psoriasis: Recommendation for patients on regular infliximab therapy.

During COVID-19 outbreak hospitals were congested and infliximab was interrupted. Thus, we performed this observational study to understand the consequent burden of complications in these special cluster of psoriatic patients. We followed up 56 psoriatic patients who were receiving Infliximab treatment by telephone. The majority of patients had lesions exacerbation, accompanied by anxiety emotion. It is suggested that reserving common drugs for psoriasis at home is necessary. Besides, telemedicine should be advocated as a main medical visit mode during the outbreak of COVID-19.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-USA Panel.

Importance: Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices. Objective: To evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV. Evidence Review: New evidence was collected since the previous International Antiviral (formerly AIDS) Society-USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations. Findings: From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic. Conclusion and Relevance: Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.

The experience of Hamad General Hospital collaborative anticoagulation clinic in Qatar during the COVID-19 pandemic.

Hamad General Hospital Anticoagulation Clinic is one of the largest collaborative-practice clinics of its type in Qatar. The patients being followed at this clinic are typically complex and vulnerable. During the coronavirus disease 2019 pandemic, measures were implemented at the clinic to minimize the exposure of patients and healthcare providers to the acute respiratory syndrome coronavirus-2 and to promote social distancing. These measures included extending INR-recall period, transitioning to direct oral anticoagulant drugs whenever feasible, home visits to elderly and immunocompromised patients for INR testing, establishing an anticoagulation hotline, and relocation of warfarin dispensing from the main pharmacy to the anticoagulation clinic. In addition, the clinic shifted its multidisciplinary team meetings onto an online platform using Microsoft Teams. Telehealth consultations were extensively utilized to closely follow up with the patients and ensure that anticoagulation efficacy and safety remained optimal. The aim of this paper is to share our experience and describe the measures adopted by the clinic as part of the Hamad Medical Corporation response to the emerging situation.