Effectiveness of biologic switching in a real-life, Belgian severe asthma cohort.

In this observational study, we show that switching biologics in severe asthma results in a high proportion of controlled patients.

Chemotherapy switch for localized pancreatic cancer: a systematic review and meta-analysis.

BACKGROUND: Patients with localized (that is non-metastatic) pancreatic ductal adenocarcinoma with an inadequate response or toxicity to first-line chemotherapy may benefit from chemotherapy switch. The aim was to explore the available data on the use and effect of chemotherapy switch, as reported in the literature. METHODS: A systematic search was conducted in Embase, MEDLINE (Ovid), the Web of Science, Cochrane, and Google Scholar on 1 December 2023. The main outcomes were the proportion of patients who underwent chemotherapy switch and the carbohydrate antigen 19-9 response and resection, R0 resection, and ypN0 resection rates after chemotherapy switch. Data were pooled using a random-effects model. RESULTS: A total of five retrospective studies, representing 863 patients with localized pancreatic ductal adenocarcinoma, were included and 226 of the 863 patients underwent chemotherapy switch. In four studies, first-line chemotherapy consisted of 5-fluorouracil/leucovorin/irinotecan with oxaliplatin ('FOLFIRINOX') and patients were switched to gemcitabine with nab-paclitaxel. Reasons for chemotherapy switch included an inadequate biochemical, clinical, or radiological response, or toxicity. Three studies compared patients who underwent chemotherapy switch with patients who only received first-line chemotherapy and found that the proportion of patients who underwent chemotherapy switch was 20.5% (95% c.i. 10.5% to 36.3%). The pooled resection rate after chemotherapy switch was 42.0% (95% c.i. 16.6% to 72.5%). Two studies compared the chance of resection after chemotherapy switch versus first-line chemotherapy alone and found a risk ratio of 0.88 (95% c.i. 0.65 to 1.18). Two studies, with a combined total of 576 patients, found similar postoperative survival for patients who underwent chemotherapy switch and patients who only received first-line chemotherapy. CONCLUSION: One in five patients with localized pancreatic ductal adenocarcinoma underwent chemotherapy switch after an inadequate response or toxicity to first-line chemotherapy. The pooled resection rate after chemotherapy switch was 42% and similar in overall survival compared with first-line chemotherapy only. Three ongoing trials are investigating chemotherapy switch in patients with an inadequate radiological or carbohydrate antigen 19-9 response.

Effectiveness of switching to subcutaneous infliximab in inflammatory bowel disease patients with inadequate biochemical response during intravenous administration.

Infliximab (IFX) has transformed the management of inflammatory bowel diseases (IBD). While intravenous (IV) IFX has been effective, a subcutaneous (SC) formulation offers advantages in convenience and cost. However, there is lack of evidence regarding the transition from IV to SC-IFX, especially for patients with inadequate responses. This study investigates the effectiveness of switching from IV to SC-IFX in patients with inadequate responses during IV maintenance therapy. A retrospective study enrolled IBD patients who transitioned to SC-IFX after demonstrating inadequate responses during IV maintenance therapy. The study collected data of demographics of patients and dose and therapies administered prior to the IV-IFX. Primary outcomes included improvements in C-reactive protein (CRP) or fecal calprotectin (FC) levels. This study evaluated the trough levels and its differences between pre- and post-switching. Among 44 patients included, 10 exhibited CRP elevation before the switch, with 6 showing normalization post-switch. Similarly, 42 patients had elevated FC levels pre-switch, with 26 experiencing reductions post-switch. Trough levels increased after the switch. However, there were no significant differences between responders and non-responders. This study is the first study to investigate the transition therapy of IV to SC-IFX in patients with inadequate response. This suggests that SC-IFX could be a viable alternative in the management of IBD. However, further research is necessary to evaluate its efficacy in a larger population of patients who exhibit inadequate responses during IV-IFX maintenance therapy.

Efficacy and safety of treat-and-extend intravitreal brolucizumab in naive and switched patients with macular neovascularization: one-year follow-up study.

BACKGROUND: to analyze, at one year, the efficacy and safety of treat-and-extend (T&E) intravitreal (IV) Brolucizumab in patients affected by macular neovascularization (MNV). Both naïve and previously treated (i.e., switched) patients were included, and the data from the two groups were compared. METHODS: anatomical (i.e., central subfoveal thickness, CST; presence of fluid), functional (i.e., best corrected visual acuity, BCVA) and treatment-related (i.e., number of IV injections within the study period; number of patients reaching a 12-weeks interval between treatments) data from 41 eyes of 41 subjects (20 naïve and 21 switched) were analyzed. Patients were treated with 3 monthly IV injections followed by a T&E regimen based on a disease activity assessment performed at each scheduled IV treatment. RESULTS: significant CST reduction (from 412.1 ± 115.8 to 273.2 ± 61.6; p < 0.05) and BCVA (mean; p) improvement were observed in the naïve group, while in the switched cohort, both parameters were almost stable. In the naïve and switched groups, 55% and 33.5% of patients, respectively, reached a 12-week IV interval at one year, with a mean of 6.55 ± 1 and 7.43 ± 0.68 IV treatments, respectively. One patient with mild anterior uveitis without sequelae was recorded. CONCLUSION: In patients with MNV, IV Brolucizumab injections following a T&E regimen demonstrated great efficacy and a good safety profile, with greater anatomical and functional results in naïve patients. TRIAL REGISTRATION: This study was approved by the Local Ethics Committee (protocol number 155/2020, general registry number n°11486, InterHospital Ethics Committee, San Luigi Gonzaga Hospital, Orbassano, Italy).

Public deliberation to assess patient views on biosimilar medication switching for the treatment of inflammatory bowel disease.

BACKGROUND: Biosimilars are highly similar, but not identical, versions of originator biologic medications. Switching patients to biosimilars presents an opportunity to mitigate rising drug costs and expand patient access to important biologic therapies. However, decreased patient acceptance and adherence to biosimilar medications have been reported, which can lead to loss of treatment response, adverse reactions, and inefficient resource utilization. Understanding patient perceptions of biosimilars and biosimilar switching is needed to inform patient-centered care strategies that promote efficient resource utilization. METHODS: We used democratic deliberation methods to solicit the informed and considered opinions of patients regarding biosimilar switching. Patients with inflammatory bowel disease (IBD; n = 29) from the Veterans Health Administration (VHA) participated in 5-hour deliberation sessions over two days. Following educational presentations with experts, participants engaged in facilitated small group discussions. Transcripts and facilitators' notes were used to identify key themes. Participants completed surveys pre- and post-deliberation to collect sociodemographic and clinical features as well as to assess IBD treatment knowledge and attitudes toward care and approaches to biosimilar switching. RESULTS: Five major themes emerged from the small group discussions in the context of biosimilar switching: 1) concerns about adverse consequences and unclear risk-benefit balance; (2) importance of communication and transparency; (3) desire for shared decision making and patient involvement in treatment decisions; (4) balancing cost-saving with competing priorities; and (5) advocating for individualized care and prioritization based on risk levels. These views led participants to favor approaches that prioritize switching the sickest patients last (i.e., those with poorly controlled disease) and that offer patients control and choices around biosimilar switching. Participants also expressed preferences for combining elements of different approaches to maximize fairness. CONCLUSIONS: Approaches to biosimilar switching should consider patients' desires for transparency and effective communication about biosimilar switching and engagement in their medical decision-making as part of patient-centered care. Incorporating patient preferences around biosimilar switching is critical when navigating the quality and affordability of care in resource constrained settings, both within the VHA and in other healthcare systems.

Generic dispensing rates for substitutable drugs prescribed by general practitioners compared with other private ambulatory specialists: A study based on a French national reimbursement database.

BACKGROUND: The use of generic drugs is a way for healthcare systems to reduce costs, particularly in ambulatory care. Several studies suggest that the prescriber's speciality is associated with the use of generic drugs, and that substitutable drugs prescribed by General Practitioners (GPs) are more often generic, but this association has never been studied in France. In the French legislative context, except in rare situations, all substitutable drugs prescribed should be dispensed in generic form. OBJECTIVES: Compare the generic drugs dispensing rate among substitutable drugs dispensed in community pharmacies prescribed by French private GPs with that of other private specialists, all other specialities combined (first objective) or each other speciality taken individually (second objective). METHODS: We used a sample of an open available semi-aggregated database from the 2019 French health insurance system database. We compared with logistic regression models GPs to all other specialities combined, then GPs to the 19 other specialties taken individually, only on the substitutable drugs they prescribe in common. RESULTS: In 2019, 53.4% of the drugs prescribed by French private ambulatory physicians were substitutable drugs, and 81.5% of them were dispensed in generic form. After adjustment, the generic dispensing rate for substitutable drugs was significantly higher for GPs than for other specialties (ORa 0.74 [IC95% 0.72-0.76]). Thirteen of the nineteen other specialities taken individually, such as endocrinologists (ORa 0.64 [IC95% 0.57-0.72]) and cardiologists (ORa 0.60 [0.56-0.63]) had significantly lower generic dispensing rates than GPs. No other speciality had a rate significantly higher than GPs. CONCLUSIONS: Substitutable drugs prescribed by French private GPs are more often dispensed in generic form than those from other private ambulatory specialties. To understand this result and optimise the use of generic drugs in outpatient settings, we need to study the different stages of drug use, from prescription by the physician to dispensing by the pharmacist and acceptance by the patient.

82% of substitutable drugs prescribed by French private general practitioners in 2019 were dispensed in generic form.No other ambulatory specialty rated significantly higher than general practitioners.Research is needed to study reasons for non-generic drug prescription in the context of legislative changes.

Should intravitreal dexamethasone implant in refractory diabetic macular edema be used as an adjuvant therapy or switch therapy?

PURPOSE: To compare the outcomes of intravitreal dexamethasone implant used as either an adjuvant or a switching therapy for diabetic macular edema in patients with poor anatomic response after three consecutive monthly injections of ranibizumab. METHODS: This retrospective study included patients with diabetic macular edema who received three consecutive doses of ranibizumab as initial therapy and demonstrated poor response. A single dose of intravitreal de xamethasone implant was administered to these patients. The patients were divided into two groups according to the treatment modalities: the adjuvant therapy group, consisting of patients who continued treatment with ranibizumab injection after receiving intravitreal dexamethasone implant, and the switch therapy group, consisting of patients who were switched from ranibizumab treatment to intravitreal dexamethasone implant as needed. The main outcome measurements were best corrected visual acuity and central retinal thickness at baseline and at 3, 6, 9, and 12 months of follow-up. RESULTS: In this study that included 64 eyes of 64 patients, the best corrected visual acuity and central retinal thickness values did not significantly differ between the groups at baseline and at 6 months of follow-up (p>0.05). However, at 12 months, the best corrected visual acuity values in the adjuvant and switch therapy groups were 0.46 and 0.35 LogMAR, respectively (p=0.012), and the central retinal thickness values were 344.8 and 270.9, respectively (p=0.007). CONCLUSIONS: In a real-world setting, it seems more reasonable to use intravitreal dexamethasone implant as a switch therapy rather than an adjuvant therapy for diabetic macula edema refractory to ranibizumab despite three consecutive monthly injections of ranibizumab. Patients switched to intravitreal dexamethasone implant were found to have better anatomic and visual outcomes at 12 months than those who continued ranibizumab therapy despite their less-than-optimal responses.

The Science of Biosimilars-Updating Interchangeability.

This Viewpoint from the US Food and Drug Administration (FDA) summarizes a recent update to an FDA draft interchangeability guidance regarding the need for clinical switching studies to illustrate the FDA's ongoing efforts to streamline the development of biosimilar medications that are in line with the latest science.

Conversion of CII Opioid Medications to Buprenorphine in the Chronic Pain Population - Insights and Clinical Pearls.

BACKGROUND: There is a great deal of confusion associated with conversion from CII opioid to buprenorphine products. The data presented supports that patients can be converted from high dose opioid medication to buprenorphine products safely and effectively. This presentation will provide a road map to help guide practitioners who are interested in applying this to their clinical practice. PURPOSE/HYPOTHESIS: Thepurposeoftheresearchwasnotonlytodiscoverifconversiontoapartialagonist CIII medication from full agonist CII medications would be achieveable without sacrificing analgesia, but also to provide guidance to providerswhoareinterestedinpursuingthisoptioninclinicalpractice. Procedures/data/observations: Patients who met inclusion criteria were stratified into subgroups on the basis of pre- conversion morphine milligram equivalents, whether they remained on opioids for breakthrough pain postconversion, and pre- and postconversion numerical rating scale pain scores. Outcomes of interest included the differences between pre- and postconversion numerical rating scale pain scores and daily morphine milligram equivalents for each sub-group. Of 157 patients reviewed, 87.9% were successfully converted to buprenor-phine buccal film. Overall, numericalrating scale pain scores were stable after conversion. Statistically significant reductions were demonstrated in the <90 daily morphine milligram equivalent subgroup. Postconversion daily morphine milligram equivalents decreased by 85.4% from baseline. Change in daily morphine milligram equivalents is representative of patients who remained on breakthrough pain medication. CONCLUSIONS/APPLICATIONS: Results demonstrate continued analgesia after conversion to buprenorphine buccal film despite reductions in daily morphine milligram equivalents. Most patients were able to convert directly from their long-acting opioid to buprenorphine buccal film and stabilized without the use of concomitant opioids for breakthrough pain. Aggressive titration strategies were associated with greater success. This data proves that conversion from full agonist CII medications is possible without sacrificing analgesia while reducing the risk of adverse events associated with full agonist CII medications.

Cognitive performance, neuropsychiatric symptoms, and cerebrospinal fluid viral control following programmatic switch from efavirenz-based to dolutegravir-based antiretroviral therapy in South Africa (CONNECT): a prospective cohort study.

BACKGROUND: Both efavirenz and dolutegravir have been associated with neuropsychiatric side-effects and cognitive impairment. Furthermore, cerebrospinal fluid (CSF) HIV RNA escape has not been comprehensively studied in African populations. We aimed to examine changes in cognition, neuropsychiatric symptoms, and CSF viral control associated with the widespread switch from efavirenz-based to dolutegravir-based antiretroviral therapy (ART). METHODS: This prospective cohort study of people with HIV and people without HIV recruited adults with HIV (aged 18-55 years) from the Gugulethu Community Health Centre in a low-income periurban area of Cape Town, South Africa. Eligible participants had been receiving efavirenz-based ART for at least 1 year and were identified by the clinic to switch to dolutegravir-based ART as part of the national programmatic switch. Participants were studied at baseline and followed up at 1 year after switch to dolutegravir. People without HIV were recruited from the same area, matched for age and gender, and followed up at the same time interval. People with HIV and people without HIV underwent comprehensive cognitive testing over seven domains and measures of functioning, mood, anxiety, and sleep. People with HIV had CSF sampling for HIV RNA quantification. FINDINGS: Between Aug 12, 2019, and Sept 16, 2022, we recruited 178 people with HIV and 95 people without HIV. 145 (81%) of 178 people with HIV and 40 (66%) of 60 people without HIV who were offered underwent follow-up. Global cognitive performance was 2·57 T score points lower in people with HIV than in people without HIV at baseline (p=0·0008). At follow-up, cognition in people with HIV improved more than practice effects observed in people without HIV (coefficient 1·40, 95% CI 0·48-2·32, p=0·0028) and no significant difference in cognitive performance between groups was apparent (51·43 vs 52·73; p=0·22). Sleep quality improved following the switch (risk ratio 0·90, 95% CI 0·84-0·95; p=0·0002), driven mainly by indicators of disturbed sleep. There were nine incident cases of depression, although baseline differences were present. There was one case (1%) of CSF escape at baseline and three cases (4%) at follow-up; all were at low levels or resolved with repeated sampling. INTERPRETATION: Improvements in cognition and sleep are probably related to switching from efavirenz. However, the possible increase in depression warrants further examination. Cognitive performance in virally supressed African people with HIV receiving dolutegravir-based therapy is similar to people without HIV. CSF escape is uncommon on both efavirenz-based and dolutegravir-based therapy. FUNDING: South African Medical Research Council and UK Medical Research Council, Newton Fund.

Plasma renin activity as a marker for predicting the antihypertensive effect of switching to sacubitril/valsartan in treated hypertensive patients: Usefulness in daily clinical practice.

The authors investigated the antihypertensive effect of sacubitril/valsartan (Sac/Val) when switching from other drugs and assessed whether brain natriuretic peptide (BNP) or plasma renin activity (PRA) before drug switching was a predictor of blood pressure lowering after switching to Sac/Val. In 92 patients with treated hypertension, clinic blood pressure, plasma BNP, and PRA were examined before and after switching to Sac/Val. Clinic systolic and diastolic blood pressures significantly decreased after drug switching to Sac/Val (p < .0001, respectively). The level before drug switching of BNP had no correlation with the change in systolic blood pressure (Δ-SBP) before and after switching to Sac/Val, but that of PRA was significantly correlated with Δ-SBP (r = .3807, p = .0002). A multiple regression analysis revealed that PRA before drug switching was an independent determinant of Δ-SBP. Our findings suggest that low PRA may become a useful marker to predict the antihypertensive effect of switching to Sac/Val in treated hypertensive patients.

A Bayesian model to analyse the association of comorbidities with biosimilar treatment retention in a non-medical switch scenario in patients with inflammatory rheumatic musculoskeletal diseases.

OBJECTIVES: To analyse clinical outcomes of a non-medical switch from originator adalimumab (ADA) to its ABP501 biosimilar (ABP) over 6 months in patients with inflammatory rheumatic musculoskeletal diseases (RMD) in relation to comorbidity as a risk factor for therapy discontinuation. METHODS: RMD patients switching from originator ADA to ABP were identified from a large routine database from October 2018 onwards. Documented clinical data at the time of non-medical switching (baseline), and at 3 and 6 months were collected. Comorbidities were represented by the Charlson Comorbidity Index (CCI) at baseline and patients were categorized based on CCI > 0. Differences in the ABP retention rate over 6 months between patients with CCI = 0 and patients with CCI > 0 were analysed using Bayesian exponential regression. RESULTS: A total of 111 patients with axial spondyloarthritis (n = 68), rheumatoid arthritis (n = 23) and psoriatic arthritis (n = 15), were identified, 74.8% of whom had continued treatment with ABP after 6 months, while a smaller proportion had either switched to another ADA biosimilar (10.8%), switched back to originator ADA (7.2%), switched to a different biologic (3.6%), or dropped out (3.6%). At baseline, a CCI > 0 was found in 38% of patients. Cardiovascular comorbidities (40%) were most prevalent followed by diseases of the skin (33%), the gastrointestinal tract (20%) and the eye (20%). ABP treatment was continued after 6 months in 74% of patients with CCI = 0 and in 76% with CCI > 0. Bayesian analysis showed only a small difference (months) in the APB continuation rate between groups (estimate 0.0012, 95% credible interval (CrI) -0.0337 to 0.0361). Adjusting for age, sex, and disease subtype revealed somewhat shorter retention rates for patients with CCI > 0, but the distribution of the difference included 0 (estimate -0.0689, 95% CrI -0.2246 to 0.0234). CONCLUSION: In a non-medical switch scenario of RMD patients, there was no evidence for a considerable difference in ABP retention rates over 6 months between comorbidity groups.

Aqueous Humor Cytokine Analysis in Age-Related Macular Degeneration After Switching From Aflibercept to Faricimab.

Purpose: To examine the changes in aqueous humor cytokine levels and clinical outcomes of switching from aflibercept to faricimab in eyes with neovascular age-related macular degeneration (nAMD). Methods: Fifty-four eyes of 54 patients with AMD undergoing treatment with aflibercept under a treat-and-extend (TAE) regimen were switched to faricimab and studied prospectively. Best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status were analyzed using optical coherence tomography. Aqueous humor was collected before and after the switch, and angiopoietin-2 (Ang-2), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) A levels were measured. Results: After switching from aflibercept to faricimab, exudative changes improved in 28 eyes (52%), remained stable in eight eyes (15%), and worsened in 18 eyes (33%). BCVA changed from 0.27 ± 0.31 to 0.26 ± 0.29 (P = 0.46), CRT decreased from 306.2 ± 147.5 µm to 278.6 ± 100.4 µm (P = 0.11), and CCT changed from 189.5 ± 92.8 µm to 186.8 ± 93.9 µm (P = 0.21). VEGF-A levels were below the detection sensitivity in many cases throughout the pre- and post-switching periods. Ang-2 significantly decreased from 23.8 ± 23.5 pg/mL to 16.4 ± 21.9 pg/mL (P < 0.001), and PlGF significantly increased from 0.86 ± 0.85 pg/mL to 1.72 ± 1.39 pg/mL (P < 0.001). Conclusions: Switching from aflibercept to faricimab in patients with nAMD may not only suppress VEGF-A but also Ang-2 and reduce exudative changes.

Patients with Persistent Mild Psoriasis after Treatment with Ustekinumab Achieved Greater Improvements in Skin Clearance and Patient-reported Outcomes after Switching to Guselkumab in the Phase 3 NAVIGATE Trial.

Mild psoriasis may be burdensome; if symptoms are inadequately controlled, switching therapy may be warranted. In the Phase 3 NAVIGATE trial, patients with moderate-to-severe plaque psoriasis received ustekinumab for 16 weeks. Patients with inadequate response (Investigator's Global Assessment [IGA] ≥ 2) were randomized to switch to guselkumab or continue ustekinumab. This post-hoc analysis evaluated the patient subgroup with residual mild psoriasis (IGA = 2) after initial ustekinumab therapy. Outcomes assessed included the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Psoriasis Symptoms and Signs Diary (PSSD). Initially, 871 patients received ustekinumab. At Week 16, 161 randomized patients had residual mild psoriasis (IGA = 2). Among guselkumab- vs ustekinumab-treated patients at Week 28, 59.0% vs 27.7% achieved PASI 90, and 50.0% vs 21.0% achieved DLQI 0/1. Mean changes from baseline in PSSD score were -44 vs -28 and -50 vs -32, respectively, with thresholds of -40 considered clinically meaningful. Mean changes in PSSD itch score were -4.6 vs -2.9, with reductions ≥ 4.0 considered clinically meaningful. Treatment differences were maintained/increased through Week 52. Among patients with residual mild psoriasis after 16 weeks of ustekinumab, those switching to guselkumab had greater improvements in skin clearance, health-related quality of life, and patient-reported symptoms and signs than those continuing ustekinumab.

CD4+/CD8+ improvement after switch from a second-generation integrase inhibitor regimen to long-acting cabotegravir and rilpivirine.

Our study assessed the CD4+/CD8+ ratio in people with HIV (PWH) switching from a second-generation integrase inhibitor regimen to long-acting cabotegravir (CAB) and rilpivirine (RPV). Over one year, we observed a significant improvement in the CD4+/CD8+ ratio; In addition, our data showed that time spent in CAB+RPV was significantly associated with an increased CD4+/CD8+ ratio. These findings suggest that long-acting therapy may enhance immune recovery, also in treatment-experienced PWH.

Switch to faricimab after initial treatment with aflibercept in eyes with neovascular age-related macular degeneration.

PURPOSE: To investigate the efficacy and outcomes of switching neovascular age-related macular degeneration (nAMD) patients from aflibercept to faricimab, focusing on visual acuity, retinal fluid management, and treatment intervals. The primary aim was to assess the early outcomes in nAMD patients refractory to aflibercept and explore faricimab's potential as a longer-lasting therapeutic alternative. METHODS: A single-center retrospective study was conducted on 50 refractory nAMD patients at Cleveland Clinic Abu Dhabi from September 2022-May 2023. Patients were switched from aflibercept to faricimab, having met specific criteria for refractory nAMD. The study analyzed best-corrected visual acuity (BCVA), central subfield thickness (CST), and fluid changes post-switch, using Optical Coherence Tomography (OCT). RESULTS: After three faricimab injections, significant reductions in CST were observed, with a notable decrease in retinal fluid. The mean BCVA remained stable throughout the study period. Although there was a decrease in the maximum pigment epithelial detachment (PED) height, it was not statistically significant. Treatment intervals post-switch showed that the majority of patients maintained or extended their treatment intervals, with a significant proportion achieving resolution of intraretinal fluid (IRF) and subretinal fluid (SRF). CONCLUSIONS: Switching to faricimab from aflibercept in refractory nAMD patients led to significant improvements in retinal fluid management and CST, with stable BCVA outcomes. Faricimab presents a promising alternative for patients requiring frequent aflibercept injections, potentially offering a more manageable treatment regimen with extended dosing intervals. This study highlights the need for personalized therapeutic strategies in nAMD treatment, though further research is necessary to optimize treatment switches.

Switching hemophilia A patients to rVIII-SingleChain: The Iberian experience.

The real-world outcomes of lonoctocog alfa (rVIII-SingleChain), a long-acting factor VIII (FVIII) with a favorable safety and efficacy profile in trials, were assessed in patients with hemophilia A in Iberian (Spain and Portugal). This was a retrospective study involving patients switching to rVIII-SingleChain from other FVIIIs in 7 Spanish and Portuguese hospitals. The efficacy and safety of replacement therapies were compared between 12 months before switching and the period from switching to the end of the study. Twenty-nine patients (median age 25 years; severe hemophilia A, 37.9%) were recruited. Before switching, 12 were on prophylaxis and were followed-up for a median of 12 months. After switching, 17 received prophylaxis with rVIII-SingleChain and were followed-up for a median of 41 months. Those with ≤2 weekly infusions increased from 37.5% before switching to 60.7% after switching to rVIII-SingleChain. The median monthly consumption was 312 IU/kg with prior FVIIIs and 273 IU/kg with rVII-SingleChain. Six spontaneous bleeds were reported in each period in the prophylaxis patients. In the entire cohort, 50 bleeds were reported with prior FVIIIs and 33 were reported after switching to rVIII-SingleChain. Patients requiring ≤1 dose for hemostasis increased from 44.0% with prior FVIIIs to 60.6% with rVIII-SingleChain. Responses were rated good/excellent in 95.4% of cases. No safety concerns were reported. Patients who switched to rVIII-SingleChain prophylaxis had excellent bleeding control and reduced infusion frequency in regular clinical practice, with the subsequent increase in quality-of-life.

Switching from inotersen to eplontersen in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: analysis from NEURO-TTRansform.

BACKGROUND: The phase 3 NEURO-TTRansform trial showed eplontersen treatment for 65 weeks reduced transthyretin (TTR), halted progression of neuropathy impairment, and improved quality of life (QoL) in adult patients with hereditary TTR-mediated amyloidosis with polyneuropathy (ATTRv-PN), vs. historical placebo. METHODS: NEURO-TTRansform enrolled patients with ATTRv-PN. A subset of patients were randomized to receive subcutaneous inotersen 300 mg weekly (Weeks 1-34) and subsequently switched to subcutaneous eplontersen 45 mg every 4 weeks (Weeks 37-81). Change in serum TTR and treatment-emergent adverse events (TEAEs) were evaluated through Week 85. Effects on neuropathy impairment, QoL, and nutritional status were also evaluated. RESULTS: Of 24 patients randomized to inotersen, 20 (83%) switched to eplontersen at Week 37 and four discontinued due to AEs/investigator decision. Absolute change in serum TTR was greater after switching from inotersen (-74.3%; Week 35) to eplontersen (-80.6%; Week 85). From the end of inotersen treatment, neuropathy impairment and QoL were stable (i.e., did not progress) while on eplontersen, and there was no deterioration in nutritional status. TEAEs were fewer with eplontersen (Weeks 37-85; 19/20 [95%] patients) compared with inotersen (up to Week 35; 24/24 [100%] patients). Mean platelet counts decreased during inotersen treatment (mean nadir reduction ‒40.7%) and returned to baseline during eplontersen treatment (mean nadir reduction, ‒3.2%). CONCLUSIONS: Switching from inotersen to eplontersen further reduced serum TTR, halted disease progression, stabilized QoL, restored platelet count, and improved tolerability, without deterioration in nutritional status. This supports a positive benefit-risk profile for patients with ATTRv-PN who switch from inotersen to eplontersen.

Siponimod from fingolimod direct switch in patients transitioning in secondary progressive multiple sclerosis: A single center case series.

INTRODUCTION: The transition from fingolimod (FIN) to siponimod (SIP) for Multiple Sclerosis (MS) treatment in the occurrence of Secondary Progressive Multiple Sclerosis (SPMS) diagnosis has increasingly attracted considerable interest in the recent literature. METHODS: We evaluated the efficacy and safety of a direct switch from FIN to SIP in nine MS patients who had switched directly from FIN to SIP due to SPMS diagnosis at the Multiple Sclerosis Center of the University Hospital Policlinico of Bari. RESULTS AND CONCLUSION: Real-world results from our cohort demonstrated that the direct switch from FIN to SIP in patients transitioning in SP course is associated with clinical and disability progression stability, with a favorable safety profile.