RESUMEN
BACKGROUND: Teprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of acute and chronic thyroid eye disease (TED) related to hyperthyroidism. Given the lower incidence of TED associated with hypothyroidism / euthyroidism, there is a paucity of data regarding the efficacy of teprotumumab in this group. METHODS: In this multicenter study, consecutive patients who had been diagnosed with TED, presenting with either hypothyroidism or euthyroidism as their baseline thyroid dysfunction and treated with teprotumumab were included. All patients had measurements of proptosis, clinical activity scores (CAS), diplopia scores and four-point strabismus scores before and after therapy. RESULTS: Twenty-six patients met the inclusion criteria. Mean age was 48 ± 14 years old and mean duration of TED prior to treatment was 31 ± 43 months. All patients received 8 infusions. Mean (SD) reduction in proptosis for study orbits was 2.7 mm (1.8) (p < 0.05) and 1.8 mm (2.0) for the fellow orbit (p < 0.05). In the study orbit, mean (SD) CAS was 2.3 (1.3) before therapy and 1.0 (1.0) following therapy (p < 0.05). At baseline, mean (SD) diplopia score was 1.2 (1.1) and 0.9 (1.1) following therapy (p < 0.05). CONCLUSION: Teprotumumab reduces proptosis and inflammation in patients presenting with TED associated with hypothyroidism and euthyroidism. The results of this study highlight the potential for teprotumumab therapy in this subgroup and also provide a unique insight into the potential role of the IGF-1R in these patients.
RESUMEN
PURPOSE: To determine the rate of re-treatment in patients who receive a full course of teprotumumab therapy for thyroid eye disease (TED) and drivers of re-treatment. DESIGN: Multicenter retrospective study. PARTICIPANTS: All patients who received a full course of treatment and had available data at 1 year after initial treatment were included. METHODS: Charts were reviewed for the following information: age, sex, months since diagnosis of TED, smoking status, and prior treatments. Further, the clinical activity score (CAS), proptosis, and the Gorman diplopia score were reviewed at baseline, at the end of the first course, and at baseline for the second course in those who received it. A logistic regression model was created to review the drivers of re-treatment. MAIN OUTCOME MEASURES: Rate of re-treatment and the drivers of re-treatment. RESULTS: One hundred nineteen patients were included from 3 centers across the United States. The overall re-treatment rate was 24% (29/119). No difference was found among the 3 sites (P = 0.6). In univariable analyses, at baseline, no difference was found in proptosis (P = 0.07), diplopia score (P = 0.4), or duration of TED (P = 0.4) between patients who were re-treated and those not re-treated. From the re-treated group, 82% showed a significant proptosis response (≥ 2-mm reduction from baseline) after the initial course, whereas 68% of patients who were not re-treated showed a clinically significant proptosis response (P = 0.16). The mean ± standard deviation difference between the end of the first treatment and at baseline before the second treatment (in those who received it) was 2 ± 2 for CAS, 2 ± 4 mm for proptosis, and 1 ± 1 for diplopia score. Age was the only significant driver of re-treatment (P < 0.05). Re-treated patients were 7 years older than patients who were not re-treated (60 years vs. 53 years; P < 0.05). CONCLUSIONS: In patients receiving a full course of teprotumumab therapy, the rate of re-treatment was 24%. Age was the only driver of re-treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
RESUMEN
Thyroid eye disease (TED) is the most common extra thyroidal manifestation of Graves' disease (GD). It may also present in those who are hypothyroid or euthyroid. The characteristic clinical manifestations of TED: chemosis, lid swelling, proptosis and diplopia are driven by a combination of inflammation and extracellular matrix modification. It has recently emerged that one of the major drivers of this molecular signature is the over-expression of the insulin like growth factor-1 receptor (IGF-1R) on key effector cells in TED pathogenesis. The overexpression of the IGF-1R is coupled with a dysregulation of the IGF-1R axis, which links other pathways that modulate inflammation, such as fibrosis and extracellular matrix organization, in patients with TED. This overexpression is also found to persist from the acute stage into the chronic phase. Teprotumumab, a fully human immunoglobulin (Ig) G1 monoclonal antibody that inhibits the IGF-1R, recently gained approval in the US for the treatment of TED. In phase 2 and phase 3 clinical studies, teprotumumab showed efficacy in reducing inflammation, proptosis, diplopia and burden on quality of life, in patients who were treated. Post introduction studies have confirmed the results of the phase 2 and phase 3 studies. Since 2020, over 5, 800 patients have been treated with teprotumumab and it appears to be well tolerated. The American Thyroid Association and the European Thyroid Association have recommended it as first line therapy for patients with moderate to severe TED, who display features of proptosis and diplopia.
RESUMEN
BACKGROUND: Teprotumumab, a novel IGF-1R antibody, has been shown to significantly reduce the signs of acute and chronic Thyroid Eye Disease (TED). Light sensitivity is a reported symptom in patients with TED. There is a lack of a prospective study that has explored the effects on light sensitivity in a large cohort of patients with acute and chronic TED following treatment with teprotumumab. METHODS: Consecutive patients who were diagnosed with TED and reported light sensitivity at baseline were considered for study eligibility. All patients had measurements of Visual Light Sensitivity Questionnaire-8 (VLSQ-8), proptosis, clinical activity score (CAS), and MRD1 (distance between the upper eyelid margin and corneal reflex, mm) and MRD2 (distance between the lower eyelid margin and corneal reflex, mm) before and after treatment. RESULTS: Ninety patients (41 acute, 49 chronic) met the inclusion criteria. The mean (SD) age was 47.3 (14.3). Eighty-six (95.6%) patients completed all 8 infusions. There was a significant reduction in the total score and across all categories of the VLSQ-8 (p < 0.01 for all). Seventy-two (80%) patients had a clinically significant improvement (≥2 reduction) in at least one category. There was no significant difference in the total VLSQ-8 score between the acute and chronic group (p = 0.8). CONCLUSION: Teprotumumab improves light sensitivity in patients with acute and chronic TED. The results of this study highlight that the improvements in light sensitivity following treatment are not directly related to the mechanical changes in TED, suggesting another underlying mechanism is potentially involved.
RESUMEN
CONTEXT: Early inflammatory thyroid eye disease (TED) can lead to symptomatic chronic disease, including disabling proptosis. Teprotumumab, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor, previously demonstrated efficacy in acute, high-inflammation TED trials. OBJECTIVE: We present data from the first placebo-controlled trial with teprotumumab in chronic/low disease activity TED. METHODS: This randomized double-masked, placebo-controlled trial, conducted at 11 US centers, enrolled adult participants with TED duration of 2 to 10 years, Clinical Activity Score (CAS) ≤ 1 or no additional inflammation or progression in proptosis/diplopia for ≥1 year, proptosis ≥3 mm from before TED and/or from normal, euthyroid/mildly hypo/hyperthyroid, no prior teprotumumab, and no steroids within 3 weeks of baseline. Patients received (2:1) intravenous teprotumumab or placebo once every 3 weeks (total 8 infusions). The primary endpoint was proptosis (mm) improvement at Week 24. Adverse events (AEs) were assessed. RESULTS: A total of 62 (42 teprotumumab and 20 placebo) patients were randomized. At Week 24, least squares mean (SE) proptosis improvement was greater with teprotumumab (-2.41 [0.228]) than with placebo (-0.92 [0.323]), difference -1.48 (95% CI -2.28, -0.69; P = .0004). Proportions of patients with AEs were similar between groups. Hyperglycemia was reported in 6 (15%) vs 2 (10%) and hearing impairment in 9 (22%) vs 2 (10%) with teprotumumab and placebo, respectively. AEs led to discontinuation in 1 teprotumumab (left ear conductive hearing loss with congenital anomaly) and 1 placebo patient (infusion-related). There were no deaths. CONCLUSION: Teprotumumab significantly improved proptosis vs placebo in longstanding/low inflammation TED, demonstrating efficacy regardless of disease duration/activity. The safety profile was comparable to that previously reported.
Asunto(s)
Exoftalmia , Oftalmopatía de Graves , Adulto , Humanos , Anticuerpos Monoclonales Humanizados/efectos adversos , Oftalmopatía de Graves/tratamiento farmacológico , Inflamación , Inhibidores de Proteínas Quinasas , Método Doble CiegoRESUMEN
PURPOSE: Teprotumumab, an insulin-like growth factor 1 receptor monoclonal antibody, is FDA-approved to treat thyroid eye disease (TED). The initial clinical trials excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose >1 gm), or prior biologic treatment. Information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED. METHODS: This is a multicenter retrospective study of all patients treated with teprotumumab for moderate-to-severe TED after failing conventional therapy with corticosteroids, orbital radiation, surgical decompression, biologics, or other steroid-sparing medications. Treatment failure was defined as an incomplete response to or reactivation after previous treatment. Only patients who received at least 4 infusions of teprotumumab were included in the analysis. Primary outcome measures comprised proptosis response (≥2 mm reduction in the study eye without a similar increase in the other eye), clinical activity score (CAS) response (≥2-point reduction in CAS), and diplopia response (≥1 point improvement in Gorman diplopia score in patients with baseline diplopia) following treatment. Adverse events and risk factors for recalcitrant disease were also evaluated. RESULTS: Sixty-six patients were included in this study, 46 females and 20 males. Average age was 59.3 years (range 29-93). The mean duration of disease from TED diagnosis to first infusion was 57.8 months. The proptosis, CAS, and diplopia responses in this recalcitrant patient population were 85.9%, 93.8%, and 69.1%, respectively. Patients experienced a mean reduction in proptosis of 3.1 ± 2.4 mm and a mean improvement in CAS of 3.8 ± 1.6. Patients who underwent prior decompression surgery experienced a statistically significant decrease in diplopia response (46.7% vs. 77.5%, p = 0.014) and proptosis response (75.0% vs. 90.9%, p = 0.045) when compared with nondecompression patients. Additionally, there were no significant differences in proptosis, CAS, and diplopia responses between patients with acute (defined as disease duration <1 year) versus chronic (disease duration ≥1 year) TED. While most adverse events were mild to moderate, 4 patients reported serious adverse events related to persistent hearing loss. CONCLUSIONS: Patients with recalcitrant TED demonstrated a significant improvement after teprotumumab in each of the primary study outcomes. The degree of proptosis reduction, diplopia response, and CAS improvement in the recalcitrant group were similar to those of treatment-naïve patients from the pivotal clinical trials. Patients with a prior history of orbital decompression, however, demonstrated poor improvement in diplopia and less reduction in proptosis than surgery naïve patients. These results indicate that teprotumumab is a treatment option for the treatment of patients with TED recalcitrant to prior medical therapies.
Asunto(s)
Blefaroplastia , Párpados , Humanos , Párpados/cirugía , Blefaroplastia/métodos , Órbita/cirugía , CaraRESUMEN
PURPOSE: This study assesses the effects of topical oxymetazoline 0.1% on eyelid position, eye redness, and patient-perceived eye appearance in patients without severe ptosis. METHODS: This is a randomized double-blinded controlled trial conducted at a single institute. Patients aged 18-100 years were randomized to receive one drop of oxymetazoline hydrochloride 0.1% or placebo bilaterally. Marginal reflex distance (MRD) 1 and 2, palpebral fissure height, eye redness, and patient-perceived eye appearance were assessed at baseline and two hours after drop instillation. Primary outcome measures included the change in MRD1, MRD2, and palpebral fissure height. Secondary outcome measures included changes in eye redness and patient-perceived eye appearance after drop instillation. RESULTS: In total, 114 patients were included, 57 treatment patients (mean age 36.4 ± 12.7 years, 31.6% male) and 57 controls (mean age 31.3 ± 10.1 years, 33.3% male). Baseline mean MRD1, MRD2, and palpebral fissure were similar between groups (p = 0.24, 0.45, and 0.23, respectively). Changes in MRD1 and eye redness in the treatment group were significantly greater than those in the control group (0.9 ± 0.9 mm vs. - 0.3 ± 0.4 mm, p < 0.001; - 2.6 ± 4.4 vs. - 0.5 ± 2.3, p = 0.002, respectively). Patient-perceived eye appearance was significantly improved in the treatment group compared to the controls (p = 0.002), with more treatment group patients also reporting increased eye size and decreased eye redness (p = 0.008, p = 0.003, respectively). There were 9 treatment-emergent adverse events (TEAEs) in 7 treatment group patients and 5 TEAEs in 5 control patients (p = 0.25), all of which were mild in severity. CONCLUSIONS: Topical oxymetazoline 0.1% increases MRD1 and palpebral fissure height, decreases eye redness, and improves patient-perceived eye appearance.
Asunto(s)
Blefaroptosis , Oximetazolina , Humanos , Masculino , Adulto Joven , Adulto , Persona de Mediana Edad , Femenino , Oximetazolina/farmacología , Párpados , Blefaroptosis/inducido químicamente , Blefaroptosis/tratamiento farmacológico , Medición de Resultados Informados por el PacienteRESUMEN
BACKGROUND: Dry eye syndrome occurs in up to 85% of patients with thyroid eye disease (TED). Lacrimal gland enlargement correlates with subjective tearing and a reduction in quality of life in patients with TED. METHODS: In this prospective longitudinal study, patients presenting for the treatment of TED were considered for eligible. Primary outcomes included a change in the volume of the lacrimal gland and the production of tears following treatment with teprotumumab. The volume of lacrimal glands and proptosis was calculated using 3D volumetric analysis. Tear production was measured by Schirmer's test and associated symptoms were assessed using the VLSQ-8. The orbit with the most proptosis was designated the study orbit and the contralateral orbit was designated the fellow orbit. RESULTS: Twenty patients were included. Mean (SD) age was 61 (18) and mean duration of TED prior to therapy was 48 months (47). Lacrimal gland volume in the study orbit decreased from 768 mm3 (288) to 486 mm3 (173) (p < 0.01) following therapy. For the fellow orbit, volume reduced from 637 mm3 (261) to 379 mm3 (147) (p < 0.01). Schirmer's test reading (STR) in the study orbit increased from 14.5 mm (8.2) to 23 mm (10) (p < 0.01) (59%) following treatment. In the fellow orbit, STR increased from 12.7 mm (7) to 21 mm (9) post therapy (69%) (p < 0.01). There was a significant improvement on all parts of the VLSQ-8. CONCLUSION: Teprotumumab significantly reduces TED related expansion of the lacrimal gland, increases tear production, and improves dry eye symptoms.
Asunto(s)
Síndromes de Ojo Seco , Exoftalmia , Oftalmopatía de Graves , Aparato Lagrimal , Humanos , Preescolar , Aparato Lagrimal/diagnóstico por imagen , Estudios Longitudinales , Estudios Prospectivos , Calidad de Vida , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/diagnóstico , Lágrimas , Oftalmopatía de Graves/tratamiento farmacológico , Oftalmopatía de Graves/diagnósticoRESUMEN
BACKGROUND: The increasing popularity of fat transfer (FT) to the lower eyelids has led to an increase in unwanted lumps, bumps, and contour irregularities (LBCs). Few studies have addressed the management of LBCs. OBJECTIVES: The aim of this study was to address the management of LBCs. METHODS: In this retrospective review, charts of all patients presenting for evaluation of LBCs following FT procedures to the lower eyelid were reviewed. Clinical characteristics on presentation and surgical findings were evaluated. Patient postoperative clinical course and complications were also documented. RESULTS: Forty-eight patients were included (45 women and 3 men), with an average follow-up of 14 months (range, 5-24 months). In 65%, LBCs manifested above the lower orbital rim (AR) and in 35% they were noted AR and below the rim (AR/BR). The type of contour deficits noted were a solitary nodule (SN) in 54%, a mixed picture (MP) in 23%, diffuse enlargement (DE) in 17%, and multiple nodules (MNs) in 6%. Combining lesion location and type of contour deficit, the most common presentation was an SN-AR in 22 patients (46%), followed by an MP-AR/BR in 8 patients (17%), and a DE-AR/BR in 5 patients (10%). Surgical findings revealed that grafted fat is consistently found separate from native eyelid/orbital fat, and within the orbicularis muscle when AR, and within the orbicularis muscle or the deep suborbicularis oculi fat when BR. CONCLUSIONS: LBCs tend to manifest in characteristic patterns with a predilection for an AR location. Recommendations on the diagnosis and management of these lesions are provided.
Asunto(s)
Blefaroplastia , Párpados , Masculino , Humanos , Femenino , Mejilla/cirugía , Párpados/cirugía , Órbita , Estudios Retrospectivos , Tejido Adiposo/trasplante , Blefaroplastia/efectos adversos , Blefaroplastia/métodosRESUMEN
PURPOSE: To review and summarize studies on the anatomy and involutional changes of the midface. METHODS: A PubMed search was performed searching for studies on the anatomy and involutional changes concerning the midface. RESULTS: The anatomy of the midface is complex. Studies of involutional change vary in scientific quality and have conflicting results. However, it appears that among the more common changes, there is a decrease in the maxillary and pyriform angle, with changes to the orbital floor position. Further, there appears to be an inferior migration of the fat compartments of the midface during aging, exacerbating the hollow of the palpebromalar groove and causing a deepening of the nasojugal groove. Changes to the volume of the buccal extension of the buccal fat pad exacerbate these changes and contribute to the gestalt changes associated with facial aging. Here, we review the major characteristics of soft tissue and bony changes on the midface, with special reference to their anatomic relationships. CONCLUSIONS: The major findings characterizing midface aging are related largely to the soft tissue. However, more robust studies are required to quantify these changes and to appraise their impact on the overall manifestation of aging.
Asunto(s)
Envejecimiento , Ritidoplastia , Humanos , Cara/anatomía & histología , Mejilla/cirugía , Órbita , Tejido Adiposo/cirugía , Ritidoplastia/métodosRESUMEN
BACKGROUND: Previous studies have attempted to explain age-related changes to the orbit in isolation, often producing conflicting results. The authors used highly accurate imaging software to analyze computed tomographic scans to characterize changes related to age objectively. METHODS: In this case-control study, patients seen in an ear, nose, and throat clinic were screened for study entry. Male and female participants were divided into two age groups (20 to 30 years and 60 to 75 years). Primary outcomes included measurement of bony orbital dimensions, volume of soft tissues (muscle and fat volume), and anterior globe position. Three-dimensional reconstructions were created of each orbit allowing these measurements. The generalized estimating equation was used so that both orbits from each patient could be included without any bias. RESULTS: The final sample included 240 orbits from 120 patients. There were 30 patients in each age group. Among female participants, the bony orbital volume ( p < 0.05), fat volume ( p < 0.01), and central width ( p < 0.001) of the bony orbit increased with age. The anterior globe position was significantly greater in older female participants ( p < 0.01). For male participants, the fat volume ( p < 0.0001) and central height ( p < 0.03) increased with age; the lateral rim moved posteriorly with age ( p < 0.007). The anterior globe position was not different between the age groups in male participants ( p = 0.56). CONCLUSION: The female bony orbit expands with age and is associated with a more anterior position of the globe; the male bony orbital volume remains the same and the lateral rim moves posteriorly.
Asunto(s)
Órbita , Procedimientos de Cirugía Plástica , Adulto , Anciano , Envejecimiento/fisiología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Órbita/diagnóstico por imagen , Órbita/cirugía , Tomografía Computarizada por Rayos X/métodos , Adulto JovenRESUMEN
BACKGROUND: Teprotumumab, a monoclonal antibody that blocks the insulin-like growth factor-1 receptor, has recently been approved by the US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED). Since its approval, aside from data on the safety and clinical efficacy of teprotumumab from Phase-2 and Phase-3 trials, only a handful of reports have been published regarding its use in the wider population. In this review, we briefly describe the mechanism of action of teprotumumab and review the literature to provide an overview of published clinical experience. This information was used to provide recommendations for patient selection, management of patient expectations, infusion details and site options, tips to optimize the authorization process, and how to monitor and mitigate side effects. EVIDENCE ACQUISITION: A systemic review of the literature was performed regarding teprotumumab, focusing on its mechanisms of action and published reports on its use on patients with TED. A review of Embase, Medline (PubMed), Web of Science, and Google Scholar was conducted. RESULTS: Clinical experience following the approval of teprotumumab has confirmed its efficacy in reducing inflammation and proptosis in patients with acute TED (<2 years). The reduction in proptosis occurs due to a reduction in orbital fat and muscle volume. Furthermore, there is evidence for its use in patients with compressive optic neuropathy. There are also reports that show its efficacy in reducing proptosis, inflammation, and diplopia in patients with chronic TED (>2 years). Teprotumumab was associated with side effects, such as muscle spasm, hearing loss, and hyperglycemia. To date, 2 case reports have shown a possible association with flares of inflammatory bowel disease. CONCLUSIONS: Teprotumumab is a powerful therapeutic option for the treatment of TED. Clinical experience following FDA approval has demonstrated efficacy in treating patients with acute and chronic TED. It is the only therapeutic option that has been shown to reduce orbital soft tissue expansion in TED. However, it is expensive, and sometimes, obtaining insurance authorization can be time consuming and difficult. Further work will reveal its full side effect profile and help to establish its role in the armamentarium used to treat TED.
Asunto(s)
Exoftalmia , Oftalmopatía de Graves , Anticuerpos Monoclonales Humanizados/uso terapéutico , Exoftalmia/tratamiento farmacológico , Oftalmopatía de Graves/tratamiento farmacológico , Humanos , Inflamación/tratamiento farmacológico , Estados UnidosRESUMEN
BACKGROUND: Teprotumumab is the first treatment for thyroid eye disease (TED), a debilitating autoinflammatory condition, approved by the Food and Drug Administration in the United States, which reduces proptosis and improves quality of life. In the absence of guidelines, clinical recommendations were developed for using teprotumumab in patients with TED in the United States. METHODS: A 3-round modified-Delphi panel was conducted between October 2020 and February 2021 with experts in the management of patients with TED. Key areas regarding the use of teprotumumab were investigated, including eligible patient populations, concomitant treatments, and assessment of response and adverse events. This used 2 survey rounds via an online questionnaire, where statements were scored using 9-point Likert scales. Statements with conflict were included in the third round, involving a consensus meeting via videoconference. RESULTS: Consensus was obtained for all statements (n = 75); of which, 56% were revised to enable agreement of the group. The consensus meeting provided agreement regarding which populations should receive teprotumumab therapy, including all adult patients with TED with a clinical activity score of ≥4. Treatment with teprotumumab can also be considered for TED patients displaying the following characteristics: a CAS of <3, lid retraction of ≥2, and mild or early optic neuropathy with close clinical observation. Further recommendations included suitability of treatment for those beyond 16 months following the initial diagnosis of TED, low CAS concomitant treatment with steroids in some cases, retreatment for those who have relapses, and finally a recommendation to continue therapy for all 8 infusions despite the lack of response by the fourth infusion. CONCLUSIONS: This work constitutes the first consensus on guidelines for the use of teprotumumab. The modified Delphi approach involved physicians with significant experience with the clinical use of teprotumumab, and recommendations were based on current evidence.
Asunto(s)
Oftalmopatía de Graves , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Consenso , Oftalmopatía de Graves/diagnóstico , Oftalmopatía de Graves/tratamiento farmacológico , Humanos , Calidad de VidaRESUMEN
Summary: Thyroid dermopathy is an uncommon manifestation of thyroid disease that impairs the quality of life in certain cases. Currently, the available treatments offer limited results and a chance of recurrence. Teprotumumab, a novel medication that results in the regression of thyroid ophthalmopathy, may have similar effects on dermopathy. We describe four patients treated with teprotumumab for their thyroid ophthalmopathy who concomitantly had dermatopathy upon initiation of their infusions. Patients improved after two to three infusions and three out of the four patients have not suffered a recurrence.Teprotumumab is a monoclonal antibody (MAB) that attenuates an inflammatory response, resulting in decreased edema and tissue expansion. Given the similarities of their pathophysiology, we believe that the resolution of thyroid dermatopathy and regression of thyroid eye disease occurs via the same mechanism. We encourage further investigation utilizing teprotumumab for patients whose dermopathy is associated with impaired quality of life. Learning points: Thyroid dermopathy (TD), an uncommon manifestation of thyroid disease, may occasionally impair function and quality of life. There are only a few treatments for TD, with limited results and high rates of recurrence. Teprotumumab is a Food and Drug Administration-approved medication used for thyroid eye disease (TED). Our patients treated with teprotumumab for TED showed improvement of TD, which demonstrates its potential use for this condition.
RESUMEN
IMPORTANCE: Thyroid eye disease can be a debilitating autoimmune disorder characterized by progressive proptosis or diplopia. Teprotumumab has been compared with placebo in randomized clinical trials, but not with intravenous methylprednisolone (IVMP), which sometimes is used in clinical practice for this condition. OBJECTIVE: To conduct a matching-adjusted indirect comparison of teprotumumab vs IVMP vs placebo. DATA SOURCES: Deidentified patient-level data from teprotumumab trials and aggregate-level data from literature on the most recommended regimen of IVMP. STUDY SELECTION: PubMed and Embase were searched for randomized/observational studies using key terms and controlled vocabulary. Full texts of eligible articles were reviewed and cataloged. DATA EXTRACTION AND SYNTHESIS: Conducted by 1 reviewer (R.A.Q.) and 1 verifier (R.B.), including study characteristics, eligibility criteria, baseline characteristics, and outcomes. MAIN OUTCOMES AND MEASURES: Changes in proptosis by millimeter and diplopia response (percentage with ≥1 grade reduction) from baseline to week 12 in patients receiving IVMP and placebo, and to week 24 in patients receiving teprotumumab. RESULTS: The search identified 1019 records, and 6 through manual searches, alerts, and secondary references. After excluding duplicates and screening full-text records, 12 IVMP studies were included in the matching-adjusted indirect comparison (11 for proptosis change [n = 419], 4 for diplopia response [n = 125], and 2 teprotumumab [n = 79] and placebo [n = 83] comparator studies). Treatment with IVMP resulted in a proptosis difference of -0.16 mm (95% CI, -1.55 to 1.22 mm) from baseline to week 12 vs placebo. The proptosis treatment difference between IVMP and teprotumumab of -2.31 mm (95% CI, -3.45 to -1.17 mm) favored teprotumumab. Treatment with IVMP (odds ratio, 2.69; 95% CI, 0.94-7.70) was not favored over placebo in odds of diplopia response; however, teprotumumab was favored over IVMP (odds ratio, 2.32; 95% CI, 1.07-5.03). CONCLUSIONS AND RELEVANCE: This meta-analysis suggests that use of IVMP is associated with a small, typically not clinically relevant, change from baseline in proptosis vs placebo, with modest changes in diplopia. While this nonrandomized comparison suggests that use of teprotumumab, compared with IVMP, is associated with greater improvements in proptosis and may be twice as likely to have a 1 grade or higher reduction in diplopia, randomized trials comparing these 2 treatments would be warranted to determine if 1 treatment is superior to the other to a clinically relevant degree.
Asunto(s)
Exoftalmia , Oftalmopatía de Graves , Anticuerpos Monoclonales Humanizados , Diplopía/diagnóstico , Diplopía/tratamiento farmacológico , Exoftalmia/tratamiento farmacológico , Oftalmopatía de Graves/diagnóstico , Oftalmopatía de Graves/tratamiento farmacológico , Humanos , Metilprednisolona/uso terapéuticoRESUMEN
BACKGROUND: Oxymetazoline hydrochloride 0.1% ophthalmic solution has recently been approved in the United States for the treatment of ptosis. OBJECTIVES: The aim of this study was to assess the upper and lower eyelid position as well as the brow position and the color of the sclera following the ophthalmic administration of oxymetazoline hydrochloride 0.1%. METHODS: In this prospective cohort study, consecutive patients presenting with ptosis received topical oxymetazoline 0.1%. The primary outcome was measurement of the upper eyelid height (margin-to-reflex distance 1 [MRD1]) and lower eyelid height (MRD2) relative to the center of pupil, along with assessment of brow height, measured on photographs at baseline and 2 hours after instillation of oxymetazoline. The secondary outcome was the assessment of the color of the sclera (eye whiteness) before and after treatment with a novel color space algorithm. RESULTS: Twenty-nine patients participated in the study. The mean [SD] MRD1 at baseline was 2.3 [0.6] mm. At 2 hours following oxymetazoline treatment, the mean MRD1 significantly increased to 4.2 [0.9] mm (Pâ <â 0.01). The mean MRD2 also significantly increased from 5.3 [0.9] mm to 5.7 [1.0] mm (Pâ <â 0.01). Brow position did not change with treatment (Pâ =â 0.4). Following treatment, the eye sclera became significantly whiter, with a mean ΔEab (color change) of 9.7 [3.9], with 57 out of 58 eyes experiencing a significant change in color. A change of ΔEab ≥2 is considered visually perceptible to the human eye. CONCLUSIONS: Within 2 hours of use, oxymetazoline significantly improves the size of the palpebral aperture (MRD1â +â MRD2) and also makes the eye appear significantly whiter.
Asunto(s)
Blefaroptosis , Oximetazolina , Estética , Párpados , Humanos , Estudios ProspectivosRESUMEN
PURPOSE: To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or who experienced a disease flare. DESIGN: The Treatment of Graves' Orbitopathy to Reduce Proptosis with Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X) is a teprotumumab treatment and re-treatment trial following the placebo-controlled teprotumumab Phase 3 Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC) trial. PARTICIPANTS: Patients who previously received placebo (n = 37) or teprotumumab (n = 14) in OPTIC. METHODS: OPTIC nonresponders or those who flared (≥2-mm increase in proptosis, ≥2-point increase in clinical activity score [CAS], or both) during follow-up were treated for the first time (previous placebo patients) or re-treated with teprotumumab in OPTIC-X with 8 infusions over 24 weeks. MAIN OUTCOME MEASURES: Proptosis response and safety. Secondary outcomes included proptosis, CAS, subjective diplopia, and quality-of-life. RESULTS: Thirty-three of 37 placebo-treated OPTIC patients (89.2%) became proptosis responders (mean ± standard deviation, -3.5 ± 1.7 mm) when treated with teprotumumab in OPTIC-X. The responses were equivalent to the OPTIC study. In these responders, proptosis, CAS of 0 or 1, and diplopia responses were maintained in 29 of 32 patients (90.6%), 20 of 21 patients (95.2%), and 12 of 14 patients (85.7%), respectively, at follow-up week 48. The median TED duration was 12.9 months versus 6.3 months in those treated with teprotumumab in the OPTIC study. Of the 5 OPTIC teprotumumab nonresponders re-treated in OPTIC-X, 2 responded, 1 showed a proptosis reduction of 1.5 mm from OPTIC baseline, and 2 discontinued treatment early. Of the OPTIC teprotumumab responders who experienced flare, 5 of 8 patients (62.5%) responded when re-treated (mean proptosis reduction, 1.9 ± 1.2 mm from OPTIC-X baseline and 3.3 ± 0.7 mm from OPTIC baseline). Compared with published double-masked trials and their integrated follow-up, no new safety signals were identified. Mild hearing impairment was reported; 4 events occurred during the first course of treatment, and 2 events reoccurred after re-treatment. CONCLUSIONS: Patients with TED of longer disease duration responded similarly to those treated earlier in the disease course. Patients with an insufficient initial response or flare may benefit from additional teprotumumab therapy. No new safety risk was identified; however additional postmarketing pharmacovigilance is ongoing.