Treatment Frequency and Dosing Interval of Ranibizumab and Aflibercept for Neovascular Age-Related Macular Degeneration in Routine Clinical Practice in the USA

<div><p>Purpose</p><p>To compare treatment patterns of intravitreal ranibizumab and aflibercept for the management of neovascular age-related macular degeneration (nAMD) in a real-world setting over the first 12 months of treatment.</p><p>Methods</p><p>A proprietary clinical database was used to identify treatment-naïve patients with nAMD in the USA with claims for ranibizumab or aflibercept between November 1, 2011 and November 30, 2013 and with follow-up of at least 12 months. Patients were considered treatment-naïve if they had no anti-VEGF treatment code for 6 months before the index date. Mean numbers of injections and of non-injection visits to a treating physician were compared between the two treatment cohorts (ranibizumab or aflibercept). In addition, the mean interval between doses was also investigated.</p><p>Results</p><p>Patient characteristics were similar for those receiving either ranibizumab (n = 5421) or aflibercept (n = 3506) at the index date. The mean (± standard deviation) numbers of injections received by patients treated with ranibizumab (4.9 ± 3.3) or aflibercept (5.2 ± 2.9) were not clinically different. The mean number of non-injection visits was 2.8 ± 2.8 and 2.1 ± 2.5 for ranibizumab and aflibercept, respectively. Mean dosing interval was 51.0 days (± 41.8 days) in patients receiving ranibizumab and 54.1 days (± 36.0 days) in those receiving aflibercept. Results were robust to sensitivity analyses for definition of treatment-naïve, length of follow-up and treatment in the index eye only.</p><p>Conclusions</p><p>Limited data exist regarding real-world treatment patterns of aflibercept for the management of nAMD. Our results suggest that, in routine clinical practice, patients receive a comparable number of injections in the first year of treatment with ranibizumab or aflibercept.</p></div

Evolution of Primary Analyses and Sensitivity Analyses Cohorts.

<p>ICD, international classification of disease code; nAMD, neovascular age-related macular degeneration; VEGF, vascular endothelial growth factor.</p

Annual Mean Number of Injections With any Anti-VEGF Treatment and Annual Mean Number of Non-injection Visits in The First Year of Therapy in Patients Starting Treatment with Ranibizumab or Aflibercept for Management of nAMD.

<p>Results are not adjusted for bilateral treatment and include patients who may have changed to another anti-VEGF treatment during the 1-year follow-up period. **<i>p</i> < 0.0001. nAMD, neovascular age-related macular degeneration; VEGF, vascular endothelial growth factor.</p

Dose Distribution of Index Medication Among Patients Receiving Ranibizumab and Aflibercept For Management of nAMD During 1-Year Follow-Up.

<p>nAMD, neovascular age-related macular degeneration.</p

Patient Demographics and Baseline Characteristics Among Patients Receiving Ranibizumab or Aflibercept for the Management of nAMD.

<p>Patient Demographics and Baseline Characteristics Among Patients Receiving Ranibizumab or Aflibercept for the Management of nAMD.</p

Number of Injections and Physician Visits Per Year.

<p>Number of Injections and Physician Visits Per Year.</p

Annual Mean Number of Injections and Annual Mean Number of Non-injection Visits in the First Year of Therapy in Patients Receiving Treatment with Ranibizumab or Aflibercept for the Management of nAMD.

<p>Results are not adjusted for bilateral treatment. **<i>p</i> < 0.0001. nAMD, neovascular age-related macular degeneration.</p

Injectable Magnetic Hydrogel Filler for Synergistic Bone Tumor Hyperthermia Chemotherapy

The therapeutic efficacy of bone tumor treatment is primarily limited by inadequate tumor resection, resulting in recurrence and metastasis, as well as the deep location of tumors. Herein, an injectable doxorubicin (DOX)-loaded magnetic alginate hydrogel (DOX@MAH) was developed to evaluate the efficacy of an alternating magnetic field (AMF)-responsive, chemothermal synergistic therapy for multimodality treatment of bone tumors. The prepared hydrogel exhibits a superior drug-loading capacity and a continuous DOX release. This multifunctionality can be attributed to the combined use of DOX for chemotherapy and iron oxide nanoparticle-containing alginate hydrogels as magnetic hyperthermia agents to generate hyperthermia for tumor elimination without the limit on penetration depth. Moreover, the hydrogel can be formed when in contact with the calcium ions, which are abundant in bone tissues; therefore, this hydrogel could perfectly fit the bone defects caused by the surgical removal of the bone tumor tissue, and the hydrogel could tightly attach the surgical margin of the bone to realize a high efficacy residual tumor tissue elimination treated by chemothermal synergistic therapy. The hydrogel demonstrates excellent hyperthermia performance, as evidenced by in vitro cytotoxicity tests on tumor cells. These tests reveal that the combined therapy based on DOX@MAH under AMF significantly induces cell death compared to single magnetic hyperthermia or chemotherapy. In vivo antitumor effects in tumor-bearing mice demonstrate that DOX@MAH injection at the tumor site effectively inhibits tumor growth and leads to tumor necrosis. This work not only establishes an effective DOX@MAH system as a synergistic chemothermal therapy platform for treating bone tumors but also sheds light on the application of alginate to combine calcium ions of the bone to treat bone defect diseases

Severe Ocular Inflammation Following Ranibizumab or Aflibercept Injections for Age-Related Macular Degeneration: A Retrospective Claims Database Analysis

<p><b><i>Purpose</i></b>: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents including ranibizumab and aflibercept are used to treat patients with ocular disorders such as neovascular age-related macular degeneration (nAMD); however, the injections are associated with rare instances of severe ocular inflammation. This study compared severe ocular inflammation rates in patients treated with ranibizumab versus aflibercept. </p> <p><b><i>Methods</i></b>: United States physician-level claims data covering an 18-month period for each therapy were analyzed. The primary analysis compared severe ocular inflammation event rates per 1000 injections. Sensitivity and subgroup analyses evaluated the impact of factors including intraocular surgery, intravitreal antibiotic administration, and previous intravitreal injections. </p> <p><b><i>Results</i></b>: The analysis included 432,794 injection claims (ranibizumab <i>n</i> = 253,647, aflibercept <i>n</i> = 179,147); significantly, more unique severe ocular inflammation events occurred in patients receiving aflibercept than ranibizumab (1.06/1000 injections, 95% confidence interval [CI], 0.91–1.21, vs. 0.64/1000 injections, 95% CI 0.54–0.74; <i>p</i> < 0.0001). Comparable results were observed for analyses of patients who had undergone glaucoma or cataract surgeries, had antibiotic-associated endophthalmitis, had non-antibiotic-associated endophthalmitis, and were non-treatment-naive. In contrast, no significant differences in severe ocular inflammation claims were recorded in treatment-naive patients who had no record of anti-VEGF treatment in the 6 months preceding the index claim. No significant change occurred in the rate of severe ocular inflammation claims over time following ranibizumab treatment. </p> <p><b><i>Conclusions</i></b>: Severe ocular inflammation was more frequent following intravitreal injection with aflibercept than with ranibizumab during routine clinical use in patients with nAMD. This highlights the importance of real-world, post-approval, observational monitoring of novel medicines, and may aid clinical decision-making, including choice of anti-VEGF agent.</p

Hypoxia Alleviated and One Photo-Triggered Thermal/Dynamic Nanoplatform for Immunogenic Cell Death-Initiated Cancer Immunotherapy

Immunogenic cell death (ICD) induced by treatment modalities like chemotherapy, radiotherapy, and photothermal and photodynamic therapy has shown great potential to improve the low response rate of various solid tumors in cancer immunotherapy. However, extensive studies have revealed that the efficacy of cancer treatment is limited by the hypoxia and immunosuppression in the tumor microenvironment (TME). To address these challenges, a hypoxia alleviated and one phototriggered thermal/dynamic nanoplatform based on MnO2@PDA/ICG-BSA (MPIB) is developed for oxygen (O2) self-supply enhanced cancer phototherapy (PT). First, MnO2 transfers intracellular overexpression H2O2 into O2 in the acidic TME through its catalase-like activity to improve the hypoxia and also provide O2 for the following photodynamic therapy. Then, under single NIR-808 nm light irradiation (called the “phototherapeutic window”), excellent photothermal and photodynamic performance of the MPIB is activated for combined PT. Finally, assisted with immune adjuvant cytosine-phospho-guanine, obvious ICD and systemic antitumor immunity was elicited in PT-treated mice and demonstrated significant growth inhibition on distant tumors. This MPIB-based nanoplatform highlights the promise to overcome the limitations of hypoxia and also challenges of immunosuppressive tumor microenvironments for improved cancer immunotherapy