Health-economic evaluation of fluocinolone acetonide 190 µg implant in people with diabetic macular edema

Abstract

Objectives: To assess healthcare resource use and costs of treating people with clinically significant diabetic macular edema (DME) with fluocinolone acetonide (FAc) 190 µg intravitreal implant in routine clinical practice.

Methods: The retrospective Iluvien Clinical Evidence (ICE-UK) study collected data on people prescribed the FAc implant in any one of 13 ophthalmology centers between April 1, 2013 and April 15, 2015. Data were collected for 12 months before and after implantation. Standard UK costs were attributed to healthcare resource use.

Results: In total, 208 people contributing 233 FAc-treated eyes were selected. Mean age was 68.1 years and 62% were male. The mean (standard deviation, SD) number of anti-vascular endothelial growth factor (anti-VEGF) injections per FAc treated eye in the 12 months prior to implant was 2.8 (2.5), decreasing to 0.6 (1.4) for the same period after implant (p?<?.001). The corresponding figures for other steroid injections (dexamethasone and triamcinolone) were 0.14 (0.4) before and 0.08 (0.4) after implant (p?=?.016). There was no statistically significant difference in the number of laser therapies required in the 12 months before and after FAc implant (mean?=?0.12 vs 0.11, respectively; p?=?.626). Overall, mean (SD) healthcare costs were £2,691 (£1,850) before and £1,239 (£1,203) after FAc implant (p?<?.001). The unit drug and administration cost per FAc implant was £5,680.

Conclusions: Excluding the cost of the FAc implant, healthcare costs were significantly reduced in the 12 months post-implant. FAc implant has a duration of 3 years. This needs to be considered when interpreting the cost associated with the FAc implant.     

Evaluation of the clinical effectiveness in routine practice of fluocinolone acetonide 190 µg intravitreal implant in people with diabetic macular edema

Abstract

Objective: The aim of the Iluvien Clinical Evidence study in the UK (ICE-UK) was to assess the real-world effectiveness of fluocinolone acetonide (FAc) 190?µg intravitreal implant for the treatment of clinically significant chronic diabetic macular edema (DME) in routine clinical practice.

Methods: This retrospective study collected data from patient medical records in 13 ophthalmology centers for people with DME prescribed FAc intravitreal implant between April 1, 2013 and April 15, 2015. Visual acuity (VA) and intraocular pressure (IOP) measurements were collected for 12 months prior to and after implant.

Results: Two hundred and eight people, contributing 233 eyes, treated with FAc implant were included. Mean age was 68.1 years and 62% were male. In the 12 months prior to FAc implant, VA declined. Median (interquartile range, IQR) VA was 0.66 (0.48–1.00) LogMAR units (equivalent to 52.0 ETDRS letters) at implant, improving to 0.60 (0.38–0.90) LogMAR units (55.0 letters) at 12 months post-implant (p?<?0.001). In total, 44%, 30%, and 18% of people achieved an improvement in ETDRS score of ≥5, ≥10, and ≥15 letters, respectively, over the same period. A small but significant (p?<?.001) increase in median IOP was observed (median?=?15.0, IQR?=?13.0–18.0?mmHg at implant to 18.0, 15.0–21.0?mmHg at 12 months). In the 12 months following implant, additional IOP-lowering therapy was prescribed in 15% of subjects previously not requiring such therapy.

Conclusion: Following FAc implant, an overall significant improvement in VA was observed over a period of 12 months, accompanied by a significant but small increase in IOP.     

Evaluation of the clinical effectiveness of fluocinolone acetonide 190 µg intravitreal implant in diabetic macular edema: a comparison between study and fellow eyes

Abstract

Objectives: To compare visual and anatomical outcomes between eyes treated with fluocinolone acetonide (FAc) 190 µg intravitreal implant for clinically significant chronic diabetic macular edema (DME) and fellow eyes not treated with FAc implant using data from the Iluvien Clinical Evidence study in the UK (ICE-UK) study.

Methods: In this retrospective cohort study, data on people attending hospital eye services and treated with the FAc implant between April 1, 2013 and April 15, 2015 were collected. Changes in visual acuity (VA), central foveal thickness (CFT) and intraocular pressure (IOP) were compared between study eyes (intervention) and fellow eyes.

Results: A total of 208 people were selected. Mean age was 68.1 years and 62% were male. Mean change in VA was ?0.09 LogMAR units for study eyes and 0.04 LogMAR units for fellow eyes at 12 months post-implant (p?<?.001). Over the same period, ≥5 letter, ≥10 letter and ≥15 letter improvements in Early Treatment Diabetic Retinopathy Study (ETDRS) score were achieved by more FAc treated eyes than by fellow eyes (41% versus 23%, p?<?.001; 28% versus 11%, p?<?.001; and 18% versus 4%, p?<?.001 at 12 months, respectively). Differences in the mean change in CFT (?113?µm versus ?13?µm, p?<?.001) and IOP (3.2?mmHg versus ?0.2?mmHg, p?<?.001) were also observed between study and fellow eyes at 12 months.

Conclusion: Visual acuity improved in study eyes over the 12 months following FAc implant and worsened in fellow eyes. Over the same period, study eyes showed a larger improvement in central foveal thickness. Intraocular pressure worsened in study eyes only. Change in visual acuity, central foveal thickness and intraocular pressure between FAc implant and the end of the 12-month follow-up period differed significantly between study and fellow eyes.     

Does sulfur-hexafluoride tamponade,as an adjunct to vitrectomy and internal-limiting-membrane peeling,suffice for the treatment of retinal detachment associated with macular hole?

Objective: To evaluate the efficacy of sulfur hexafluoride tamponade, as an adjunct to vitrectomy and internal-limiting-membrane peeling, for the treatment of retinal detachment (RD) associated with macular hole (MH).

Materials and methods: Our study was a retrospective interventional case series. We evaluated 9 phakic eyes of 9 consecutive patients with retinal detachment secondary to macular hole (MHRD) treated with 20-gauge (g) pars plana vitrectomy, which was followed with trypan blue–assisted internal-limiting-membrane peeling, fluid–air exchange, and 20% sulfur hexafluoride tamponade (SF₆) gas exchange. All patients underwent optical coherence tomography, best-corrected visual acuity (BCVA) measurement, and dilated fundus examination with indentation, pre- and postoperatively.

Results: The mean (± standard deviation) follow-up time was 13 ± 3 months (range 9–18). Postoperatively, all eyes demonstrated an attached retina, whereas MH closure was achieved in only 1 eye, and in a second eye after additional injection of gas and further posturing. The BCVA improved from 2.2 ± 0.4 logMAR (logarithm of the minimum angle of resolution) at baseline to 2.0 ± 0.5 logMAR at the end of follow-up (p?=?.05).

Conclusion: The failure in MH closure in most of our cases strengthens the view that short-term tamponade with SF₆ may not suffice for achieving MH closure, and either prolonged tamponade (with C₃F₈ or silicone oil) or additional photocoagulation may be a better option for eyes with MHRDs. In addition, it is possible that intravitreal injection of gas might be an option for the treatment of persistent MHs after vitrectomy for MHRD, especially when the MH is small. Further studies are required to evaluate the above findings, although the implementation of large series studies remains a challenge because of the rarity of cases with MHRDs.     

Intravitreal pegaptanib sodium (Macugen?) for treatment of diabetic macular oedema: a morphologic and functional study

AIMS

To study whether morphologic (foveal thickness, FT) variations of clinically significant macular oedema (CMO) in patients suffering from diabetes following intravitreal pegaptanib sodium (IVP) injection were associated with functional [macular sensitivity (MS) and colour discrimination (CD)] changes.

METHODS

A longitudinal, interventional, non-randomized study was performed. FT was assessed by optical coherence tomography (OCT), MS by microperimetry, best-corrected visual acuity (BCVA) by early treatment diabetic retinopathy study charts (ETDRS) and CD by Farnswoth-Munsell test. The treatment protocol consisted of three consecutive injections (0.3 mg/0.05 ml; baseline, week 6 and week 12). Follow-up checks were scheduled at 18, 24, 36 and 48 weeks, after injections.

RESULTS

Thirty eyes of 30 patients with clinically significant CMO were included for analysis. After IVP a significant decrease of FT occurred with a mean reduction from baseline of 56.9% (P= 0.0001). An improvement of functional parameters was recorded in all patients (BCVA from 18.2 ± 8.5 letters to 25.5 ± 8.4 letters, P < 0.005, MS from 8.6 ± 2.16 dB to 10.6 ± 2.61 dB, P < 0.001, colour analysis from 376.1 ± 125.6 TES to 116 ± 34.6 TES, P= 0.0001). A statistically significant correlation between FT and BCVA as well as MS and CD was also found. Neither ocular nor systemic adverse events were reported.

CONCLUSIONS

Intravitreal pegaptanib significantly reduced FT, with a concomitant improvement of MS and CD. This association emphasizes the efficacy of IVP in the treatment of CMO.     

Estradiol vaginal inserts (4 µg and 10 µg) for treating moderate to severe vulvar and vaginal atrophy: a review of phase 3 safety,efficacy and pharmacokinetic data

Objective: To review safety, efficacy and pharmacokinetic (PK) data from the phase 3 REJOICE trial, which evaluated a 17β-estradiol (E2) softgel vaginal insert approved in 2018 for moderate to severe dyspareunia associated with menopausal vulvar and vaginal atrophy (VVA).

Methods: REJOICE (Clinicaltrials.gov: NCT02253173) was a randomized, double-blind, placebo-controlled trial in which women with moderate to severe dyspareunia due to menopausal VVA received 4 µg, 10 µg or 25 µg of an E2 vaginal insert or placebo for 12 weeks. The published data for the recently approved 4 µg and 10?µg doses of the E2 vaginal insert, including four co-primary efficacy endpoints (change from baseline to week 12 in percentages of superficial and parabasal cells, vaginal pH and severity of dyspareunia), safety and PK (which included serum E2 levels measured by gas chromatography and tandem mass spectrometry), are summarized here.

Results: Women were randomized to receive the E2 vaginal insert (4?µg [n?=?186] or 10?µg [n?=?188]; Imvexxy^a) or placebo (n?=?187) in the modified intention-to-treat population. The E2 vaginal insert (4?µg and 10?µg) significantly improved the percentages of superficial and parabasal cells (p?<?.0001), vaginal pH (p?<?.0001), and the severity score for dyspareunia (p?<?.05) from baseline to week 12 compared with placebo. The recently approved E2 vaginal insert was well tolerated, with no clinically significant differences in treatment-emergent or serious adverse events versus placebo. Systemic absorption of E2 with both doses was minimal.

Conclusions: The recently FDA-approved E2 softgel vaginal insert (4?µg and 10?µg) was safe and effective over 12 weeks for treating moderate to severe dyspareunia due to menopausal VVA with minimal systemic E2 levels.     

Simultaneous induction of non-neoplastic and neoplastic lesions with highly proliferative hepatocytes following dietary exposure of rats to tocotrienol for 2 years

It was recently shown that 1-year chronic exposure of rats to tocotrienol (TT) induced highly proliferative liver lesions, nodular hepatocellular hyperplasia (NHH), and independently increased the number of glutathione S-transferase placental form (GST-P)-positive hepatocytes. Focusing attention on the pathological intrinsic property of NHH, a 104-week carcinogenicity study was performed in male and female Wistar Hannover rats given TT at concentrations of 0, 0.4 or 2% in the diet. The high-dose level was adjusted to 1% in both sexes from week 51 because the survival rate of the high-dose males dropped to 42% by week 50. At necropsy, multiple cyst-like nodules were observed, as in the chronic study, but were further enlarged in size, which consequently formed a protuberant surface with a partly pedunculated shape in the liver at the high dose in both sexes. Unlike the chronic study, NHH was not always accompanied by spongiosis, and instead angiectasis was prominent in some nodules. However, several findings in the affected hepatocytes such as minimal atypia, no GST-P immunoreactivity and heterogeneous proliferation, implied that NHH did not harbor neoplastic characteristics from increased exposure despite sustained high cell proliferation. On the other hand, in the high-dose females, the incidence of hepatocellular adenomas was significantly higher than in the control. There was no TT treatment-related tumor induction in any other organs besides the liver. Thus, the overall data clearly suggested that NHH is successively enlarged by further long-term exposure to TT, but does not become neoplastic. In contrast, TT induces low levels of hepatocellular adenomas in female rats.     

Association of baseline C-reactive protein and prior anti-tumor necrosis factor therapy with need for weekly dosing during maintenance therapy with adalimumab in patients with moderate to severe Crohn’s disease

Abstract

Objective:

A post hoc analysis of data from the adalimumab Crohn’s disease (CD) maintenance trial (CHARM, NCT00077779), examining the relationship between adalimumab dosing and maintenance of remission and response in subgroups stratified by previous anti-TNF use and baseline CRP.     

Indications for an alternative effective treatment of head and neck squamous cell carcinoma with temsirolimus plus bevacizumab: from bench to bedside?

Head and neck squamous cell carcinoma (HNSCC) is a group of tumors known to be sensitive to chemotherapy and radiotherapy in patients who are treatment naive. However, when recurrences do occur, these tumors generally become resistant and objective responses to therapy at that point tend to be less effective. There has been an increasing interest in developing novel molecular-targeted agents that specifically modulate growth factor and signaling pathways that are unregulated in HNSCC tumor cells. Combinations of vascular endothelial growth factor and mammalian target of rapamycin inhibitors have been used in some types of neoplasms, but no such efforts have been made in HNSCC. In this study, we investigated the in vitro, in vivo, and clinical effects of the temsirolimus (mammalian target of rapamycin inhibitor, Tem) and bevacizumab (antivascular endothelial growth factor antibody, Bev) combination. In-vitro studies were carried out on the A431 human squamous epidermoid carcinoma cell line and in-vivo studies were carried out on A431 tumor cells implanted on female Nu/Nu*nuBR (athymic nude) mice. Also, the effectiveness of the Tem and Bev combination was tested clinically in two separate clinical cases of chemoresistant HNSCC. The in-vitro, in-vivo, and clinical results showed that this combination can be significantly effective. In conclusion, we discuss the theoretical basis of the molecular pharmacological interactions between Bev and Tem that could explain these good results. If the therapeutic index is ultimately well determined, the antitumor effect of Bev and Tem is very likely to yield fruitful results.     

Optical coherent tomography for in vivo determination of changes in hair cross section and diameter during treatment with glucocorticosteroids--a simple method to screen for doping substances?

Eighty percent of hair follicles are in the growing phase. They grow approximately 0.3 mm/day. The hair follicles are surrounded by a close network of capillaries, which supplies them with nutrients. It is well known that substances which influence the metabolic processes of humans also influence hair growth. Steroids, which are used for doping in sport, are among these substances. In the present paper, optical coherent tomography is used for the analysis of changes in the hair structure during the application of steroids for the treatment of patients suffering from auto-immune diseases. Significant differences in the hair cross section could be detected during treatment, while the shape of the hairs was not influenced. It could be demonstrated that optical coherence tomography is a suitable, non-invasive and low-cost measuring technique that can be applied for doping control and screening. As a result of this screening process, only those athletes who show abnormalities in hair parameters would need to be investigated by classical analytical methods. The results presented in this study are not only important for doping controls, but also for several clinical applications, such as therapy and compliance control in cases where the applied substances induce changes in the hair structure.