ABSTRACT
Introduction: Ofatumumab was approved in the United States (US) for relapsing multiple sclerosis (MS) in August 2020. Objectives: The key objective of social media listening (SML) was to understand the perceptions and sentiments of stakeholders (patients, healthcare providers [HCPs], payers, and advocacy groups) in the US for ofatumumab as a treatment for MS in the first 6 months post-approval in the real-world. Aims: To capture stakeholder conversations related to differentiation, efficacy, side-effects, drivers of adoption/switching, and compare the overall sentiment of ofatumumab to the currently available treatments. Methods: English-language social media content (e.g. open platforms: Twitter, Blogs, Forums, Facebook, Instagram, search analysis via Google) between August 2020-February 2021 was searched employing pre-defined systematic criteria. Using natural language processing, posts were indexed using the patient lexicon and were sorted by relevance, followed by a further manual evaluation to generate insights. Results: In all, there were 8895 MS disease-modifying therapy (DMT) specific posts from key stakeholders of which 1036 (11.6%) were specific to ofatumumab. Major themes for ofatumumab across all stakeholders i.e., patients, HCPs, and advocacy (n=1036) were the route of administration (n=337), efficacy (n=262), and safety (n=223). Stakeholders (HCPs and patients) emphasised the benefits associated with in-home administration, amidst the COVID-19 pandemic (viewed ofatumumab as COVID friendly). Most patients who discussed self-injection relayed their positive experiences with the ofatumumab autoinjector (62%) being painless, fast, and easy to use. High efficacy for ofatumumab mostly resonated by data on reduction in lesions and relapse activity. Most commonly reported side effects (n=66) were feeling sick (21%), fatigue (20%), and headache (17%). Side effects were reported to subside with time and subsequent doses of treatment. For overall perception, ofatumumab had the second most positive sentiment after ocrelizumab (given more familiarity) among all DMTs driven by tolerability, efficacy, and convenience. The most common reason for switching to ofatumumab among posts from patients (n=319) was flexibility/convenience and at home administration (n=116), efficacy (n=112), and ease of injection (n=39). Conclusions: Insights revealed using SML strengthens our understanding of patient experiences and perception of ofatumumab for the treatment of MS.
ABSTRACT
Introduction: Ofatumumab is a self-administered subcutaneous CD20 monoclonal antibody approved in the United States (US) in August 2020 (in the pandemic era) for the treatment of relapsing multiple sclerosis (MS) in adults. Since US approval, there is a lack of information available on the real-world utilisation of ofatumumab. Objectives: To understand the overall profile of MS patients initiating ofatumumab in the real-world clinical practice using data from a nationally representative claims database in the first 6 months post-approval. Aims: To evaluate patient demographics, treatment status, geographical distribution, premedication use, claims-based disability levels, disease-modifying therapy (DMT) use in the year prior, and corresponding median time to transition (treatment gap) for patients initiating ofatumumab. Methods: This retrospective cohort study used IQVIA opensource claims data. Adults with a diagnosis of MS who initiated ofatumumab from August 2020-February 2020 were included. The index date was defined based on the first prescription fill for ofatumumab, and the baseline period was 1-year prior to the index date. Results: Overall, 1015 patients initiating ofatumumab were included in the study. Mean (± standard deviation [range]) age was 48.2±12.3 (18-85) years, and 72.5% were females. Approximately, 33% of patients were ≥55 years of age. Most patients were from the Southern and Western regions of the US. Ofatumumab was mostly prescribed by neurologists (86.8%) vs PCP/NP/PAs. The proportion of patients with moderate to severe MS disability was 38.2%. Common comorbidities among patients were osteoarthritis (31.3%), hypertension (16.7%), and depression (12.2%). Overall, 54.8% were not on any DMT in the year prior to initiating ofatumumab. Patients commonly switched from ocrelizumab (24.2%), dimethyl fumarate (23.3%), platform injectables (19.3%) and teriflunomide (14.8%). The median transition period for dimethyl fumarate, teriflunomide, and ocrelizumab was 62, 51, and 174 days, respectively. Patients received ofatumumab pre-and post-COVID and influenza vaccine. Steroid and antihistamine use as premedication was minimal (≤2.5% of patients). Conclusions: In the real-world pandemic environment, ofatumumab was prescribed, also beyond the trial population. Most patients newly initiated ofatumumab had no treatment in the prior year. Understanding patient profile, prior DMT use in the realworld may help stakeholders guide treatment decisions.
ABSTRACT
Background and Aim: Proteases catalyze irreversible post-translational modifications that often alter biological function of the substrate. The protease dipeptidyl peptidase-4 (DPP-4) is a pharmacological target in type 2 diabetes and is abundant in liver. DPP-4 and its sister protease, fibroblast activation protein (FAP), are potential pharmacological targets in steatosis, insulin resistance, cancers, and inflammatory and fibrotic diseases. Recently, DPP-4 has been identified as a potential binding target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein.1,2 A detailed understanding of protein structure, function, and molecular interactions requires a reliable protocol for the large-scale production of highly stable and pure protein. We aimed to optimize production and purification strategies for soluble recombinant human DPP-4 and FAP from Spodoptera frugiperda 9 (Sf9) insect cells. Methods: The Bac-to-Bac Baculovirus Expression System (ThermoFisher) was used. Soluble DPP-4 (residues 29-766) was purified by a four-step procedure: differential ammonium sulfate precipitation, hydrophobic interaction chromatography, dye affinity chromatography in tandem with immobilized metal affinity chromatography, and ion exchange chromatography. Soluble FAP (residues 27-760) was expressed similarly, except for adding a gp67 secretion signal, and then purified similarly. The binding affinities of DPP-4 to the SARS-CoV-2 full-length spike protein and its receptor binding domain were measured using surface plasmon resonance. Results: This optimized DPP-4 purification procedure yielded, on average, 1.36 mg of pure fully active soluble DPP-4 protein per liter of suspension insect cell culture with specific activity 36.4 U/mg. DPP-4 activity greater than 20 U/mg indicates that the enzyme is completely pure. No specific binding between DPP-4 and CoV-2 protein was detected. For FAP, a novel baculovirus expression construct was designed and used to generate abundant active soluble recombinant human FAP expression in Sf9 insect cells for protein purification. Unexpectedly, FAP and DPP-4 behaved differently in hydrophobic interaction chromatography. Nevertheless, soluble FAP was partially purified using a similar purification protocol to DPP-4. Compared with our previous work,3 the DPP-4 now has greater yield and purity, and the FAP has greater yield. Conclusion: A procedure for high-yield DPP-4 that is purified to homogeneity was achieved and used to show that, unlike in Middle East respiratory syndrome (MERS), SARS-CoV-2 does not bind DPP-4. A better understanding of FAP behavior in liquid chromatography was obtained and will be useful for developing an optimized purification strategy.