The effectiveness and safety of switching therapy with an original drug to biosimilars in treatment of inflammatory bowel diseases

Introduction. Inflammatory bowel diseases are a group of chronic, immune-mediated diseases of unknown etiology. Etiotropic therapy of IBD does not exist, all drugs used to treat IBD have a pathogenetic effect. In the treatment of IBD biologic therapy is used. The most previously registered group of biologics are anti-TNF-α. But, after the expiration of the relevant patents, biosimilars appeared on the market (analogs, comparable in quality to the already approved reference product).Materials and methods. A retrospective study was conducted on the basis of the Ryzhikh Natianal Medical Research Centre for Coloproctology of the Ministry of Health of the Russia, which included 46 patients who switched from therapy with the original infliximab or adalimumab to biosimilar therapy.Discussion. This study showed that when switching therapy with the original drugs infliximab and adalimumab to biosimilars, the effectiveness of therapy does not significantly decrease with the use of biosimilars Infliximab BIOCAD and Dalibra. However, a statistically significant decrease in efficacy was revealed when switching from therapy with the original Infliximab to Flammegis. Considering that the use of biosimilars can reduce the cost of treatment and reduce the burden on the health budget, it is necessary to continue this study in order to obtain longer-term results.

P539 Unmet needs in advanced therapy-naïve (ATN) and advanced therapy-experienced (ATE) moderate-to-severe (mod-sev) ulcerative colitis (UC) patients in the United States (US)

Background About a third of patients with mod-sev UC receiving advanced therapy (AT, i.e. biologics and tofacitinib) do not respond initially and another third lose response. We examined reasons for treatment choice and outcomes in ATN and ATE mod-sev UC patients. Methods A point-in-time survey of US gastroenterologists and their respective consulting UC patients was conducted from Jan 2020–Feb 2021 (ongoing) using the Adelphi Disease Specific Programme™ for Inflammatory Bowel Disease. Physicians completed patient record forms for UC patients with a history of mod-sev disease covering treatment history and clinical status. Patients were classified as ATN and ATE based on treatment. Response to treatment status was identified by factor and cluster analyses using flare, remission and change in symptoms. Descriptive and comparative statistics were calculated for reasons for initiating/switching therapy and patient-reported outcomes (satisfaction, pain/fatigue, and quality of life via the EuroQol-5 dimension questionnaire [EQ-5D]). Results Based on the interim sample, 66 physicians and 394 mod-sev UC patients were analysed. Of patients who were ATN (n=82) and ATE (n=312), 29% and 32% were classified as non-responders respectively. Comparing ATN vs ATE patients, mean age was directionally lower (38.4 vs 40.7 years), proportion of males was directionally higher (65% vs 55%), and mean time since diagnosis was similar (3.9 vs 3.8 years). In general, non-responders experienced gastrointestinal-related (90% vs 41%), anorectal (38% vs 6%), and fatigue-related symptoms (66% vs 23%) more frequently than responders. ATN patients eligible to receive AT (n=26) reported dislike of injections/infusions (46%) or unwillingness to go to infusion centres (31%) as reasons for not receiving AT. Most common reasons for switching therapy in ATN patients were disease progression (40%) and lack of tolerability (27%), and in ATE patients were loss of response over time (43%) and disease progression (35%). In the ATE group, patient and physician satisfaction rates were higher in responders vs non-responders (>93% vs <79%), pain and fatigue scores were lower (0.8 vs 2.3 and 1.1 vs 2.3, p<0.0001), and EQ-5D scores higher (0.93 vs 0.81, p=0.005). In the ATN group, comparisons were not conducted due to small sample sizes. Conclusion In this point-in-time survey study with data collected during the COVID-19 pandemic period, about a third of mod-sev UC patients did not respond to current therapy. These results suggest an opportunity for new therapies that increase response rates, provide long-term disease control, provide alternatives to parenteral routes of administration, and enhance patient satisfaction.

Issues of switching therapy when effect of biological genetically engineered drugs escapes

The escape effect or secondary ineffectiveness of genetically engineered bio-drugs GEBD determines the change in patient management tactics, including switching to another genetically engineered drug. In clinical practice, this is a rather difficult task, which primarily concerns the choice of the next drug. The solution to the problem of secondary inefficiency can be achieved, for example, by switching to a GIBP with a different mechanism of action. In the VOYAGE 1, 73% of patients who did not respond to 48 weeks of adalimumab therapy achieved a PASI response of 90 by the 100th weeks after switching to guselkumab therapy. In the VOYAGE 2 study, 75 and 43% of patients achieved PASI 90 and 100 at week 100 after switching to gumelkumab therapy from adalimumab with failure at 28 weeks. In the NAVIGATE study, the increase in efficacy in patients with an insufficient response to ustekinumab when switching to guselcumab therapy was 27% (p < 0.001) when assessing the proportion of patients who achieved PASI 90 by 52nd weeks of therapy. Thus, the data of clinical trials make it possible to recommend guselkumab as the drug of choice in the case of the “escape” effect or insufficient effectiveness of GEBDs of other classes. The experience of using guselkumab in real clinical practice has shown its high efficiency in patients with the «escape effect» of anti-TNF-α and anti-IL‑17 drugs.

Experience of using a genetically engineered biological drug biosimilar in patients with rheumatoid arthritis in real clinical practice

The article presents the data of the Moscow Unified Arthritis Register (MUAR) and the results of rituximab therapy in patients with rheumatoid arthritis (RA).Aim: to evaluate the efficacy and safety of switching from the original rituximab (MabThera®) to its biosimilar (Acellbia®) in patients with RA in real clinical practice.Patients and Methods: patients with RA, included in MUAR register, were evaluated with an assessment of therapy efficacy and safety with the original rituximab (MabThera®), as well as after switching to the rituximab biosimilar (Acellbia®). A standard examination was performed to determine the number of swollen and tender joints, erythrocyte sedimentation rate, and C-reactive protein. Treatment efficacy was assessed using the DAS28 composite index, HAQ-DI (Health Assessment Questionnaire Disability Index) and RAPID-3 (Routine Assessment of Patient Index Data 3). In terms of safety, adverse events were recorded based on patient reports.Results: switching therapy regimen of 46 patients with RA from the original rituximab to the biosimilar was not accompanied by a decrease in the treatment efficacy. There was statistically significant increase in the proportion of the patients with low disease activity (DAS28<3.2) from 39.1% to 52.2% and remission (DAS28<2.6) from 17.4% to 23.9%, respectively. Further positive dynamics of HAQ-DI and RAPID-3 indices were noted. According to the authors, the increase in the frequency of a positive response to the treatment was associated with the duration of rituximab use in general. The frequency of adverse events during therapy with the original rituximab and its biosimilar was comparable: 9.22 and 10.9 per 100 patient years respectively.Conclusion: there were no significant differences between the original rituximab and its biosimilar. The results of switching therapy regimen of patients with RA from the original rituximab (MabThera®) to its biosimilar (Acellbia®), observed in real clinical practice, confirm their therapeutic equivalence.KEYWORDS: rheumatoid arthritis, rituximab, biosimilar, real clinical practice.FOR CITATION: Zhilyaev E.V., Koltsova E.N., Shmidt E.I. et al. Experience of using a genetically engineered biological drug biosimilar in patients with rheumatoid arthritis in real clinical practice. Russian Medical Inquiry. 2020;4(8):492–497. DOI: 10.32364/2587-6821-2020-4-8-492-497.

Improved Central Nervous System Symptoms in People with HIV without Objective Neuropsychiatric Complaints Switching from Efavirenz to Rilpivirine Containing cART

Objective: Occult central nervous system (CNS) symptoms not recognized by people living with HIV (PLWH) receiving efavirenz or their clinicians could occur and impact people’s quality of life. The aim of this study was to determine whether CNS parameters improve in PLWH when switching from efavirenz to rilpivirine. Methods: PLWH receiving tenofovir disoproxil fumarate, emtricitabine, efavirenz (Atripla™) with undetectable HIV RNA, and no CNS symptoms were switched cART to tenofovir disoproxil fumarate, emtricitabine, rilpivirine (Eviplera™). CNS parameters including sleep, anxiety, and depressive symptoms were evaluated using patient-reported outcome measures at baseline, 4, 12, and 24 weeks after switching therapy. A median CNS score was derived from the sum of CNS toxicities of all the grades collected in the study questionnaires. Cognitive function was assessed using a computerized test battery. Results: Of 41 participants, median age was 47 years, Interquartile range (IQR) 31, 92% were male and 80% were of white ethnicity. A significant reduction in total CNS score (10 to 7) was observed at 4 weeks (p = 0.028), but not thereafter. Significant improvements in sleep and anxiety were observed 4, 12 and 24 weeks after switching therapy (p < 0.05). No significant change in global cognitive scores was observed. Conclusions: Switching from efavirenz to rilpivirine based regimens in virologically suppressed PLWH without perceived CNS symptoms was well tolerated and slightly improved overall CNS symptoms.

Switching therapy in patients with age-related macular degeneration, diabetic macular edema and cistoid macular edema due to retinal vein occlusion

Introduction. Intravitreal injection of anti-vascular endothelial growth factor(VEGF) agents has revolutionized the management of age-related maculardegeneration (AMD), diabetic macular edema (DME), macular edemain retinal vein occlusions (RVO), and other retinal diseases accompanied byneovascular and macular edema. The aim of the study is to show the effectof switching from bevacizumab to aflibercept in patients with recalcitrantwet AMD as the best clinical approach and regimen for patients with neovascularand macular edema accompanied retinal diseases.Methods. All our patients received the intravitreal injections of 1.25 mg(0.1 mL) bevacizumab as the first treatment option, and we switched toaflibercept or triamcinolon acetonid when the therapy including bevacizumabseemed not to be effective enough, according to visual acuity andoptical coherent tomography (OCT) findings.Case presentations. We presented four cases: two patients with wet AMD,one patient with macular edema due to central retinal vein occlusion (CRVO)and one patient with DME in non-proliferative diabetic retinopathy (nPDR).The majority of our patients felt visual and anatomical improvement. Somepatients felt anatomical improvement although their visual acuity did notimprove. Switch to aflibercept had prolonged the positive effect of bavacizumabfor approximately 2 months. When regular therapy including bevacizumabwas reintroduced, the therapeutic effect would be prolonged.The effective clinical approach was not only the switching therapy but thecombination therapy as well. Individual treatment approach and pro renata regimen were most commonly used in our patients.Conclusion. Switching anti-VEGF drug showed positive results in patientswith refractory or recurrent wet AMD and macular edema.