Anti-VEGF Treatment Patterns for Neovascular Age-Related Macular Degeneration Among Medicare Beneficiaries




Purpose


To examine the use of anti–vascular endothelial growth factor (VEGF) therapy in clinical practice among patients with neovascular age-related macular degeneration (AMD).


Design


Retrospective cohort study.


Methods


Among 459 237 Medicare beneficiaries, we identified anti-VEGF treatment using claims for intravitreal injections of anti-VEGF medications with a supporting diagnosis of neovascular AMD. We used the cumulative incidence function to calculate the frequency of anti-VEGF treatments and treatment visits for neovascular AMD per treated eye in the first and second year after the initial anti-VEGF injection. We calculated the mean number of treatments and treatment visits per eye using the mean frequency function. Rates of discontinuation were estimated using Kaplan-Meier methods.


Results


The mean number of injections was 4.3 in the first year, with 58% of patients receiving 1–4 injections, 20% receiving 5–6 injections, and 22% receiving 7 or more injections. Among patients who received 7 or more injections during the first year, 31% received a comparable number during the second year, and 12% received no injections. Of patients who received 1–4 injections during the first year, 70% received no injections and 24% received 1–4 injections during the second year. Rates of anti-VEGF discontinuation were 57% within 12 months and 71% within 24 months.


Conclusions


The frequency of anti-VEGF injections for neovascular AMD was lower than that recommended by large-scale clinical trials, and rates of discontinuation were high. National practice patterns in anti-VEGF therapy for patients with neovascular AMD do not reflect optimal treatment strategies suggested by recent clinical trial evidence.


Several large multicenter, randomized clinical trials have shown that patients with neovascular age-related macular degeneration (AMD) benefit from frequent intravitreous injections of anti–vascular endothelial growth factor (VEGF). However, the benefit depends on the frequency of treatment. To maintain gains in visual acuity, patients should receive follow-up examinations more than quarterly and should be treated frequently. For example, patients receiving either ranibizumab or bevacizumab as needed required 7–8 injections in the first year and 5–6 injections in the second year for sustained improvement in visual acuity, and monthly dosing was superior to treatment as needed. Thus, clinical trials suggest that the most efficacious treatment strategy for sustained improvement in visual acuity consists of a minimum of approximately 7 anti-VEGF injections in the first year and 5 injections in the second year, coupled with frequent follow-up examinations and rigorous, objective retreatment criteria based on examination and imaging, such as optical coherence tomography.


Little is known about whether national practice patterns reflect the findings of recent clinical trials regarding the frequency of treatment and follow-up examinations for patients with neovascular AMD. Therefore, we sought to describe patterns of anti-VEGF treatment for neovascular AMD among Medicare beneficiaries who initiated therapy between 2006 and 2010, including the number of injections, the frequency of treatment visits, and the rate of discontinuation.


Methods


Data Sources


We obtained Medicare standard analytic claim files from the US Centers for Medicare & Medicaid Services. Medicare is the primary health insurer for the US population 65 years and older. All beneficiaries receive Medicare Part A benefits, which include inpatient care, and over 90% enroll in Medicare Part B, which helps cover medically necessary outpatient services. We obtained longitudinal claim files and denominator files for all fee-for-service Medicare beneficiaries who had at least 1 claim with a diagnosis of neovascular AMD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] diagnosis code 362.52) between January 1, 2004, and December 31, 2010. For this analysis, we used Medicare Part B outpatient claims files, which contain claims from outpatient institutional providers, and carrier claims files, which contain claims from noninstitutional professional providers (eg, physicians), including claims for injectable medications. The denominator files include demographic characteristics, information about Medicare eligibility and enrollment, and death dates, if applicable. The institutional review board of the Duke University Health System approved this study.


Study Population


The study population included all eyes in which patients received an anti-VEGF injection for neovascular AMD between January 1, 2005, and December 31, 2010. To identify the study population, we first selected all outpatient and carrier claims for intravitreous injections (Current Procedural Terminology [CPT] code 67028) of bevacizumab or ranibizumab and a supporting diagnosis of neovascular AMD. To identify the medications associated with intravitreous injections, we first searched for medication-specific Healthcare Common Procedure Coding System (HCPCS) medication reimbursement codes. For periods during which medication-specific codes were not available, we identified the medications by using nonspecific reimbursement codes in combination with reimbursement amounts from the Medicare quarterly pricing reports ( Supplemental Table 1 , available at AJO.com ). Using modifier codes present on each injection claim, we determined which eye was treated. We considered the date of the earliest observed anti-VEGF treatment per eye to be the index anti-VEGF treatment date for that eye. We restricted the analysis to beneficiaries who were 65 years or older and living in the United States on the index date. To help ensure that we were observing the first anti-VEGF treatment associated with each eye, we also required that the index date follow a 1-year period of continuous fee-for-service Medicare enrollment without claims for anti-VEGF therapy.


Treatment and Discontinuation


We searched outpatient and carrier claims in the 2 years after the index date for procedures related to the management of neovascular AMD. Specifically, we searched for intravitreous injections of anti-VEGF agents, identified as described above, and optical coherence tomography (OCT) procedures (CPT code 92135). We defined anti-VEGF treatment as a claim for an intravitreous injection of an anti-VEGF agent. We defined a treatment visit as a claim for either anti-VEGF treatment or OCT. We defined discontinuation of anti-VEGF therapy as the absence of anti-VEGF treatment for at least 12 months, and discontinuation of AMD treatment visits as the absence of treatment visits for at least 12 months. We considered discontinuation of therapy to begin on the first day of the 12-month period.


Other Variables


To understand the demographic and clinical characteristics of patients in the study population at the time of treatment initiation, we used age, sex, and race information from the denominator files and indicators of ocular comorbid conditions—cataracts, glaucoma, diabetic macular edema, and diabetic retinopathy—for the index year. We defined cataracts and glaucoma using the Chronic Condition Warehouse indicators. We searched claims from the index year for diagnoses of diabetic macular edema (ICD-9-CM diagnosis code 362.07 or a combination of code 362.53 or 362.83 with code 250.xx on the same claim) and diabetic retinopathy (ICD-9-CM code 362.01 or 362.02) and for treatment with photodynamic theraphy (CPT code 67221 or 67225) or thermal laser photocoagulation (CPT codes 67220 or 0017T).


Statistical Analysis


We describe the baseline characteristics of patients in the study population at the time of the first anti-VEGF treatment by presenting frequencies with percentages for categorical variables and means with SDs for continuous variables. We present these characteristics by patient and by treated eye. Patients who initiated treatment in both eyes during the study period contributed data twice to the eye-specific analyses, corresponding to the timing of the initial injection in each eye.


We calculated the frequency of anti-VEGF treatments and treatment visits for neovascular AMD per treated eye in the first and second year after initial treatment using the cumulative incidence function. We considered both anti-VEGF treatments and treatment visits to be recurring events, enabling us to categorize patients into the following groups according to treatment intensity: none (0 injections or visits), low frequency (1–4 injections or visits), medium frequency (5–6 injections or visits), and high frequency (7 or more injections or visits). We calculated the mean number of treatments and treatment visits per eye using the mean frequency function. Both the cumulative incidence and mean frequency functions account for the competing risk of mortality and the fact that follow-up differs across patients as a result of data censoring. We defined the date of censoring as the earlier of December 31, 2010, or the date on which the patient died or enrolled in Medicare managed care, if applicable. Among patients with at least 12 months of data after initiation of anti-VEGF treatment (ie, those who initiated treatment before January 1, 2010), we estimated rates of discontinuation using Kaplan-Meier methods. We used SAS version 9.2 (SAS Institute Inc, Cary, North Carolina, USA).




Results


A total of 459 237 Medicare beneficiaries initiated anti-VEGF treatment for neovascular AMD in 621 547 eyes between January 1, 2006, and December 31, 2010. Table 1 shows the baseline characteristics of the study population. The mean age was approximately 81 years, 64% of the patients were women, and 96% were white. The most commonly observed ocular comorbid conditions were cataract and glaucoma. Initial anti-VEGF treatment medication was bevacizumab for 66% of the patients and ranibizumab for 34%.



Table 1

Baseline Characteristics of Medicare Beneficiaries Receiving Anti–Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration












































































Variable Patients (N = 459 237) Treated Eyes (N = 554 965)
Age, mean (SD), y 81.2 (6.9) 81.4 (6.8)
Male, n (%) 165 051 (35.9) 196 376 (35.4)
Race, n (%)
Black 5625 (1.2) 6291 (1.1)
White 442 022 (96.3) 535 107 (96.4)
Other/unknown 11 590 (2.5) 13 567 (2.4)
Ocular comorbid conditions, n (%)
Cataracts 130 671 (28.5) 153 447 (27.6)
Diabetic macular edema 34 410 (7.5) 40 941 (7.4)
Diabetic retinopathy 25 029 (5.5) 29 335 (5.3)
Glaucoma 72 647 (15.8) 86 353 (15.6)
Initial anti-VEGF medication, n (%)
Bevacizumab 369 245 (66.5)
Ranibizumab 185 720 (33.5)
AMD treatment in prior year, n (%)
Photodynamic therapy 28 004 (5.0)
Thermal laser photocoagulation 8478 (1.5)

AMD = age-related macular degeneration; VEGF = vascular endothelial growth factor.


In the first year after initial treatment, 59% of treated eyes received 1–4 injections and 22% received 7 or more injections ( Table 2 ), with an overall mean of 4.3 injections. The frequency of treatment was higher among patients who initiated treatment with ranibizumab than among those who initiated treatment with bevacizumab. The frequency of treatment in the first year increased somewhat during the study period, from an average of 3.8 injections among patients initiating therapy in 2006 to an average of 4.8 injections among patients initiating therapy in 2010 ( Supplemental Table 2 , available at AJO.com ).



Table 2

Frequency of Anti–Vascular Endothelial Growth Factor Treatment per Treated Eye After Initial Anti–Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration Among Medicare Beneficiaries, Overall and By Initial Anti–Vascular Endothelial Growth Factor Treatment






















































































































































































Anti-VEGF Treatment in Prior Year No. of Eyes at Start of Year Frequency of Anti-VEGF Treatment in Current Year, N (%) a Anti-VEGF Injections, Mean
None (0 injections) Low (1–4 injections) Medium (5–6 injections) High (≥7 injections)
Overall
First year after initial treatment
No injections 554 965 0 (0.0) 354 093 (58.7) 100 228 (19.6) 100 644 (21.7) 4.3
Second year after initial treatment
Low frequency (1–4 injections) 239 240 173 662 (70.4) 55 175 (24.3) 7467 (3.8) 2936 (1.5) 0.9
Medium frequency (5–6 injections) 79 999 28 022 (31.5) 36 835 (44.8) 10 255 (15.7) 4887 (7.9) 2.6
High frequency (≥7 injections) 89 404 14 143 (12.4) 37 274 (33.7) 17 424 (22.9) 20 563 (30.9) 4.8
Initial treatment with bevacizumab
First year after initial treatment
No injections 369 245 0 (0.0) 253 032 (63.7) 63 031 (18.8) 53 182 (17.5) 4.0
Second year after initial treatment
Low frequency (1–4 injections) 171 102 124 240 (70.3) 39 710 (24.5) 5160 (3.7) 1992 (1.5) 0.8
Medium frequency (5–6 injections) 50 387 16 859 (29.7) 23 752 (45.6) 6654 (16.5) 3122 (8.2) 2.7
High frequency (≥7 injections) 46 836 7497 (12.1) 20 173 (34.7) 9206 (23.6) 9960 (29.6) 4.8
Initial treatment with ranibizumab
First year after initial treatment
No injections 185 720 0 (0.0) 101 061 (49.0) 37 197 (21.0) 47 462 (29.9) 5.0
Second year after initial treatment
Low frequency (1–4 injections) 68 138 49 422 (70.5) 15 465 (23.8) 2307 (4.0) 944 (1.7) 0.9
Medium frequency (5–6 injections) 29 612 11 163 (34.6) 13 083 (43.6) 3601 (14.5) 1765 (7.4) 2.5
High frequency (≥7 injections) 42 568 6646 (12.8) 17 101 (32.7) 8218 (22.3) 10 603 (32.3) 4.9

AMD = age-related macular degeneration; VEGF = vascular endothelial growth factor.

a Percentages were calculated using the cumulative incidence function.



In the second year after treatment initiation, the frequency of treatment differed according to the frequency of treatment in the first year ( Table 2 ). Among eyes receiving 7 or more injections in the first year, 54% received 5 or more injections in the second year (mean, 4.8 injections). By comparison, among eyes receiving 4 or fewer injections in the first year, 5% received 5 or more injections in the second year and more than 70% received no injections (mean, 0.9 injections). Results were similar by initial treatment medication and by year of treatment initiation ( Supplemental Table 2 ).


Table 3 shows the frequency of treatment visits per treated eye. During the first year of anti-VEGF treatment, 49% of eyes were associated with 7 or more visits and 30% were associated with 1–4 visits. Among the eyes associated with 7 or more visits in the first year, 65% were associated with 5 or more visits during the second year. In contrast, among the eyes associated with 1–4 visits in the first year, 9% were associated with 5 or more visits in the second year and 54% were associated with no visits in the second year. Results were similar by initial treatment medication and by year of treatment initiation ( Supplemental Table 3 , available at AJO.com ).



Table 3

Frequency of Age-Related Macular Degeneration Treatment Visits per Treated Eye After Initial Anti–Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration Among Medicare Beneficiaries
































































































































































Anti-VEGF Treatment in Prior Year No. of Eyes at Start of Year Frequency of Anti-VEGF Treatment Visits in Current Year, N (%) a
None (0 injections) Low (1–4 visits) Medium (5–6 visits) High (≥7 visits)
Overall
First year after initial treatment
No visits 554 965 0 (0.0) 207 269 (30.0) 116 796 (21.2) 230 900 (48.8)
Second year after initial treatment
Low frequency (1–4 visits) 118 822 67 268 (53.6) 42 272 (37.2) 5857 (5.7) 3425 (3.5)
Medium frequency (5–6 visits) 86 334 23 491 (23.3) 43 350 (49.2) 11 397 (15.7) 8096 (11.8)
High frequency (≥7 visits) 203 487 18 956 (6.2) 76 371 (29.1) 38 238 (20.6) 69 922 (44.1)
Initial treatment with bevacizumab
First year after initial treatment
No visits 369 245 0 (0.0) 153 945 (34.2) 80 321 (22.4) 134 979 (43.5)
Second year after initial treatment
Low frequency (1–4 visits) 90 000 50 585 (53.1) 32 547 (37.8) 4351 (5.7) 2517 (3.4)
Medium frequency (5–6 visits) 60 013 15 659 (21.9) 30 556 (49.7) 8145 (16.3) 5653 (12.1)
High frequency (≥7 visits) 118 312 11 291 (6.1) 46 010 (29.9) 22 758 (21.4) 38 253 (42.6)
Initial treatment with ranibizumab
First year after initial treatment
No visits 185 720 0 (0.0) 53 324 (21.7) 36 475 (18.9) 95 921 (59.4)
Second year after initial treatment
Low frequency (1–4 visits) 28 822 16 683 (55.3) 9725 (35.1) 1506 (5.9) 908 (3.7)
Medium frequency (5–6 visits) 26 321 7832 (26.3) 12 794 (48.2) 3252 (14.3) 2443 (11.2)
High frequency (≥7 visits) 85 175 7665 (6.3) 30 361 (28.1) 15 480 (19.5) 31 669 (46.0)

AMD = age-related macular degeneration; VEGF = vascular endothelial growth factor.

a Percentages are calculated using the cumulative incidence function.



Discontinuation of anti-VEGF therapy was common ( Table 4 and Figure ). When we defined discontinuation as a period of at least 12 months without anti-VEGF treatment, 17% of patients discontinued therapy after the initial treatment, 57% discontinued therapy within 12 months, and 71% discontinued therapy within 24 months. When we defined discontinuation as a period of at least 12 months without a treatment visit for neovascular AMD (ie, a visit for anti-VEGF treatment or OCT), rates of discontinuation were significantly lower, at 5% after the first treatment, 29% within 12 months, and 42% within 24 months.



Table 4

Proportion of Treated Eyes for Which Treatment Was Discontinued Among Medicare Beneficiaries Receiving Anti–Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration a




























Months After Initial Anti-VEGF Treatment Discontinuation of Anti-VEGF Treatment, N (%) Discontinuation of AMD Treatment Visits, N (%)
0 71 259 (17.4) 19 984 (4.9)
6 174 094 (44.7) 73 257 (19.1)
12 213 645 (57.4) 104 199 (29.1)
18 234 239 (65.6) 122 981 (36.6)
24 244 743 (71.0) 133 486 (42.1)

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Jan 8, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Anti-VEGF Treatment Patterns for Neovascular Age-Related Macular Degeneration Among Medicare Beneficiaries
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