Real-World Experience with Lifitegrast Ophthalmic Solution (Xiidra^®) in the US and Canada: Retrospective Study of Patient Characteristics, Treatment Patterns, and Clinical Effectiveness in 600 Patients with Dry Eye Disease

Figures & data

Table 1 Healthcare Provider (HCP) Survey (n=501)

HCP and Practice Characteristics
Clinical practice setting, n (% [95% CI])
Academic-based	40 (8.0 [5.8, 10.7])
Community-based	80 (16.0 [12.9, 19.5])
Private practice	416 (83.0 [79.5, 86.2])
Size of practice, n (% [95% CI])
Solo (1 ophthalmologist or optometrist)	104 (20.8 [17.3, 24.6])
Small (2–10 ophthalmologists or optometrists)	312 (62.3 [57.9, 66.5])
Medium (11–50 ophthalmologists or optometrists)	78 (15.6 [12.5, 19.0])
Large (≥51 ophthalmologists or optometrists)	7 (1.4 [0.6, 2.9])
Number of years in practice, n (% [95% CI])
<1 year	2 (0.4 [0.0, 1.4])
1–5 years	60 (12.0 [9.3, 15.1])
6–10 years	118 (23.6 [19.9, 27.5])
11–20 years	170 (33.9 [29.8, 38.3])
>20 years	151 (30.1 [26.1, 34.4])
Number of unique DED patients seen per year
Mean ± SD [median] (95% CI of mean)	393.0 ± 304.5 [300.0] (366.3, 419.7)
Percentage of unique DED patients seen per year treated with lifitegrast
Mean ± SD [median] (95% CI of mean)	20.3 ± 20.7 [14.0] (18.5, 22.1)
Treatment Practices
Timing of lifitegrast prescription, n (% [95% CI])
After DED diagnosis and prior to prescribing other therapies treating symptoms of DED	68 (13.6 [10.7, 16.9])
After DED diagnosis and in combination with other therapies treating symptoms of DED	180 (35.9 [31.7, 40.3])
Following treatment with other therapies treating DED symptoms	253 (50.5 [46.0, 55.0])
Average time between DED diagnosis and lifitegrast prescription, n (% [95% CI])
<1 month	38 (7.6 [5.4, 10.3])
1–3 months	154 (30.7 [26.7, 35.0])
4–6 months	198 (39.5 [35.2, 44.0])
7–12 months	63 (12.6 [9.8, 15.8])
1–2 years	31 (6.2 [4.2, 8.7])
>2 years	17 (3.4 [2.0, 5.4])
Reasons for lifitegrast prescription, n (% [95% CI])^a
Efficacy	288 (57.5 [53.0, 61.9])
Immediate relief of symptoms	137 (27.3 [23.5, 31.5])
Improvement in signs	151 (30.1 [26.1, 34.4])
Tolerability	138 (27.5 [23.7, 31.7])
Patient preference	76 (15.2 [12.1, 18.6])
Insurance coverage	148 (29.5 [25.6, 33.7])
Failure of other treatments	267 (53.3 [48.8, 57.7])
Other^b	2 (0.4 [0.0, 1.4])

Notes: ^aHCPs were allowed to select more than one category. ^bOther reasons for prescription included “coupon use making it more affordable” and “plugs”.

Abbreviations: CI, confidence interval; HCP, healthcare provider; SD, standard deviation.

Table 2 Demographic and Clinical Characteristics in the Pre-Index Period Among Patients with DED Treated with Lifitegrast (n=600)

Demographic Characteristics
Age (years) at index date, mean ± SD [median] (95% CI of mean)	57.1 ± 12.8 [58.3] (56.1, 58.1)
Age (years) at index date, n (% [95% CI])
18–34	34 (5.7 [4.0, 7.8])
35–49	129 (21.5 [18.3, 25.0])
50–64	278 (46.3 [42.3, 50.4])
65–69	70 (11.7 [9.2, 14.5])
70–74	50 (8.3 [6.2, 10.8])
75–79	25 (4.2 [2.7, 6.1])
80–84	8 (1.3 [0.6, 2.6])
≥ 85	6 (1.0 [0.4, 2.2])
Female, n (% [95% CI])	455 (75.8 [72.2, 79.2])
Clinical Characteristics
Year of DED diagnosis, n (% [95% CI])
≤ 2015	88 (14.7 [11.9, 17.8])
2016	71 (11.8 [9.4, 14.7])
2017	136 (22.7 [19.4, 26.2])
2018	185 (30.8 [27.2, 34.7])
2019	78 (13.0 [10.4, 16.0])
Unknown	42 (7.0 [5.1, 9.3])
HCP who made the first DED diagnosis, n (% [95% CI])
Ophthalmologist	332 (55.3 [51.3, 59.4])
Optometrist	262 (43.7 [39.7, 47.7])
Physician	4 (0.7 [0.2, 1.7])
Other	0 (0.0)
Unknown	2 (0.3 [0.0, 1.2])
Cause/type of DED, n (% [95% CI])
Evaporative deficiency	536 (89.3 [86.6, 91.7])
Blepharitis	211 (39.4 [35.2, 43.6])
Ectropion	4 (0.7 [0.2, 1.9])
Entropion	1 (0.2 [0.0, 1.0])
Exposure to smoke, wind, or a very dry climate	93 (17.4 [14.2, 20.8])
Looking at a computer screen for a long time, reading, or other activities that reduce blinking	238 (44.4 [40.1, 48.7])
Meibomian gland dysfunction	362 (67.5 [63.4, 71.5])
Refractive eye surgery (eg, LASIK, PRK, etc)	55 (10.3 [7.8, 13.1])
Thyroid disease	19 (3.5 [2.1, 5.5])
Using contact lenses for a long time	87 (16.2 [13.2, 19.6])
Aqueous deficiency	192 (32.0 [28.3, 35.9])
Graft vs host disease	8 (4.2 [1.8, 8.0])
Lupus	9 (4.7 [2.2, 8.7])
Medication use (eg, diuretics, beta-blockers, antihistamines, sleeping pills, antidepressants)	107 (55.7 [48.4, 62.9])
Rheumatoid arthritis (and other auto-immune conditions)	45 (23.4 [17.6, 30.1])
Sjögren’s syndrome (primary and secondary)	35 (18.2 [13.0, 24.4])
Other^a	10 (1.7 [0.8, 3.0])
None of the above	28 (4.7 [3.1, 6.7])
Unknown	1 (0.2 [0.0, 0.9])
Evaporative deficiency only	376 (62.7 [58.7, 66.5])
Aqueous deficiency only	32 (5.3 [3.7, 7.4])
Both evaporative and aqueous deficiency	160 (26.7 [23.2, 30.4])
Ocular diseases/conditions, n (% [95% CI])
Amblyopia	7 (1.2 [0.5, 2.4])
Cataract	203 (33.8 [30.1, 37.8])
Glaucoma	33 (5.5 [3.8, 7.6])
Macular degeneration	24 (4.0 [2.6, 5.9])
Previous ocular injury	15 (2.5 [1.4, 4.1])
Strabismus	3 (0.5 [0.1, 1.5])
Other^b	29 (4.8 [3.3, 6.9])
None of the above	334 (55.7 [51.6, 59.7])
Unknown	2 (0.3 [0.0, 1.2])
DED-related comorbidities, n (% [95% CI])
Acne rosacea	41 (6.8 [4.9, 9.2])
Allergies (eg, environmental, dietary, drug, latex, etc)	114 (19.0 [15.9, 22.4])
Anxiety	63 (10.5 [8.2, 13.2])
Depression	63 (10.5 [8.2, 13.2])
Diabetes	82 (13.7 [11.0, 16.7])
Fibromyalgia	21 (3.5 [2.2, 5.3])
Hypercholesterolemia	42 (7.0 [5.1, 9.3])
Hypertension	163 (27.2 [23.6, 30.9])
Rheumatoid arthritis	35 (5.8 [4.1, 8.0])
Sjögren’s Syndrome	21 (3.5 [2.2, 5.3])
Sleep apnea	21
Thyroid dysfunction	43 (7.2 [5.2, 9.5])
None of the above	172 (28.7 [25.1, 32.5])
Unknown	1 (0.2 [0.0, 0.9])
Contact lenses usage, n (% [95% CI])
Daily disposable	72 (12.0 [9.5, 14.9])
Weekly disposable	30 (5.0 [3.4, 7.1])
Monthly disposable	40 (6.7 [4.8, 9.0])
Disposable soft	13 (2.2 [1.2, 3.7])
Extended wear	4 (0.7 [0.2, 1.7])
Gas permeable	8 (1.3 [0.6, 2.6])
None of the above	438 (73.0 [69.3, 76.5])
Unknown	1 (0.2 [0.0, 0.9])
Self-reported screen time per day, n (% [95% CI])
< 1 hour	52 (8.7 [6.5, 11.2])
1–3 hours	149 (24.8 [21.4, 28.5])
4–6 hours	197 (32.8 [29.1, 36.8])
7–9 hours	126 (21.0 [17.8, 24.5])
10–12 hours	21 (3.5 [2.2, 5.3])
>12 hours	3 (0.5 [0.1, 1.5])
Unknown	52 (8.7 [6.5, 11.2])

Notes: ^aOther causes/types of DED included acne rosacea, allergies, diabetes, lacrimal gland radiation, lagophthalmos, post-chemotherapy, postmenopausal, and tear film abnormalities. ^bOther ocular diseases and conditions included allergic conjunctivitis, anatomically narrow angles, blepharitis, chalazion, conjunctivochalasis, corneal dystrophy, dermatochalasis, diabetic retinopathy, drusen, epiretinal membrane, filamentary keratitis, giant papillary conjunctivitis, keratoconus, lagophthalmos, penetrating keratoplasty, posterior vitreous detachment, pseudophakia, pterygium, recurrent corneal erosion, retinal detachment, retinal hole, Stevens–Johnson syndrome, superficial punctate keratitis, and uveitis.

Abbreviations: CI, confidence interval; DED, dry eye disease; LASIK, laser-assisted in-situ keratomileusis; PRK, photoreactive keratectomy; SD, standard deviation.

Table 3 Lifitegrast Utilization Among Patients with DED

Year of index treatment initiation, n (% [95% CI])
2017	9 (1.5 [0.7, 2.8])
2018	281 (46.8 [42.8, 50.9])
2019	310 (51.7 [47.6, 55.7])
Time from DED diagnosis to lifitegrast initiation, months, mean ± SD [median] (95% CI of mean)^a
Overall	23.3 ± 42.7 [11.6] (19.8, 26.9)
Index treatment initiation in 2017 (n=8)	31.5 ± 55.0 [6.7] (not reported)
Index treatment initiation in 2018 (n=265)	23.8 ± 35.3 [12.0] (19.5, 28.0)
Index treatment initiation in 2019 (n=285)	22.7 ± 48.4 [10.0] (17.0, 28.3)
Prescription/Pack prescribed for first prescription
Days’ supply
Mean ± SD [median] (95% CI of mean)	59.7 ± 37.2 [30.0] (56.5, 62.8)
Unknown, n (% [95% CI])	60 (10.0 [7.7, 12.7])
Number of refills
Mean ± SD [median] (95% CI of mean)	4.8 ± 3.0 [4.0] (4.6, 5.1)
Unknown, n (% [95% CI])	34 (5.7 [4.0, 7.8])
Number of patients with at least 6 months of follow-up, n (% [95% CI])	554 (92.3 [89.9, 94.3])
Patients with ongoing lifitegrast treatment at 6-months post-index, n (% [95% CI])
Overall	512 (92.4 [89.9, 94.5])
Index treatment initiation in 2017 (n=8)	8 (100.0 [63.1, 100.0])
Index treatment initiation in 2018 (n=267)	241 (90.3 [86.1, 93.5])
Index treatment initiation in 2019 (n=279)	263 (94.3 [90.9, 96.7])
Number of patients with at least 12 months of follow-up, n (% [95% CI])	281 (46.8 [42.8, 50.9])
Patients with ongoing lifitegrast at 12-months post-index, n (% [95% CI])
Overall	238 (84.7 [79.9, 88.7])
Index treatment initiation in 2017 (n=8)	8 (100.0 [63.1, 100.0])
Index treatment initiation in 2018 (n=235)	195 (83.0 [77.6, 87.6)]
Index treatment initiation in 2019 (n=38)	35 (92.1 [78.6, 98.3])
Number of patients who discontinued lifitegrast, n (% [95% CI])	76 (12.7 [10.1, 15.6])
Treatment duration, months, mean ± SD [median] (95% CI of mean)	5.5 ± 3.8 [5.0] (4.7, 6.4)
Treatment duration, n (% [95% CI])
0 to ≤3 months	24 (31.6 [21.4, 43.3])
>3 to ≤6 months	20 (26.3 [16.9, 37.7])
>6 to ≤9 months	16 (21.1 [12.5, 31.9])
>9 months	16 (21.1 [12.5, 31.9])
Reasons for treatment discontinuation, n (% [95% CI])^b
Insufficient response	34 (44.7 [33.3, 56.6])
Intolerance of treatment	25 (32.9 [22.5, 44.6])
Patient preference	22 (28.9 [19.1, 40.5])
Issue with insurance coverage	18 (23.7 [14.7, 34.8])
Other	8 (10.5 [4.7, 19.7])
Unknown	3 (3.9 [0.8, 11.1])

Notes: ^aForty two patients were missing information on the date of DED diagnosis and were excluded from the calculation. ^bReasons for treatment discontinuation were calculated among the 76 patients who discontinued treatment with lifitegrast. Patients could have ≥1 reason for index treatment discontinuation. Therefore, the sum of percentages may exceed 100%. Other reasons for discontinuing lifitegrast included out of pocket cost, developed cyst, symptom resolution, sign resolution, and bad taste.

Abbreviations: CI, confidence interval; DED, dry eye disease; NR, not reached; SD, standard deviation.

Figure 1 Proportion of patients with DED-related treatments in the 6-month pre-index period and added to lifitegrast in the post-index period (n=600)*. Vertical bars indicate 95% confidence intervals. Patients may have multiple DED-related treatments; therefore, the sum of percentages may exceed 100%. *11 patients (1.8%) switched from lifitegrast to other therapies during the post-index period. These patients are not included in Figure 1.

Table 4 Patients with DED Symptoms Reported in the Pre- and Post-Index Periods

	Pre-Index n=600 n (% [95% CI])	3-Months (± 30 Days) Post-Index n=571 n (% [95% CI])	6-Months (± 30 Days) Post-Index n=534 n (% [95% CI])	12-Months (± 60 Days) Post-Index n=320 n (% [95% CI])	Any Time 0–6 Months Post-Index n=513 n (% [95% CI])
Blurred vision	346 (57.7 [53.6, 61.7])	28 (4.9 [3.3, 7.0])	25 (4.7 [3.1, 6.8])	11 (3.4 [1.7, 6.1])	59 (11.5 [8.9, 14.6])
Depression	55 (9.2 [7.0, 11.8])	8 (1.4 [0.6, 2.7])	6 (1.1 [0.4, 2.4])	9 (2.8 [1.3, 5.3])	11 (2.1 [1.1, 3.8])
Eye dryness	525 (87.5 [84.6, 90.0])	47 (8.2 [6.1, 10.8])	37 (6.9 [4.9, 9.4])	16 (5.0 [2.9, 8.0])	107 (20.9 [17.4, 24.6])
Fatigue	82 (13.7 [11.0, 16.7])	4 (0.7 [0.2, 1.8])	0 (0.0)	1 (0.3 [0.0, 1.7])	10 (1.9 [0.9, 3.6])
Foreign body sensation	299 (49.8 [45.8, 53.9])	13 (2.3 [1.2, 3.9])	9 (1.7 [0.8, 3.2])	8 (2.5 [1.1, 4.9])	29 (5.7 [3.8, 8.0])
Headache	19 (3.2 [1.9, 4.9])	1 (0.2 [0.0, 1.0])	1 (0.2 [0.0, 1.0])	0 (0.0)	3 (0.6 [0.1, 1.7])
Itching	93 (15.5 [12.7, 18.6])	9 (1.6 [0.7, 3.0])	7 (1.3 [0.5, 2.7])	2 (0.6 [0.1, 2.2])	15 (2.9 [1.6, 4.8])
Ocular burning/stinging	336 (56.0 [51.9, 60.0])	25 (4.4 [2.9, 6.4])	17 (3.2 [1.9, 5.0])	8 (2.5 [1.1, 4.9])	65 (12.7 [9.9, 15.9])
Ocular pain	73 (12.2 [9.7, 15.1])	4 (0.7 [0.2, 1.8])	3 (0.6 [0.1, 1.6])	2 (0.6 [0.1, 2.2])	8 (1.6 [0.7, 3.0])
Photophobia/sensitivity to light	57 (9.5 [7.3, 12.1])	1 (0.2 [0.0, 1.0])	1 (0.2 [0.0, 1.0])	1 (0.3 [0.0, 1.7])	4 (0.8 [0.2, 2.0])
Asymptomatic	5 (0.8 [0.3, 1.9])	28 (4.9 [3.3, 7.0])	16 (3.0 [1.7, 4.8])	17 (5.3 [3.1, 8.4])	42 (8.2 [6.0, 10.9])
Other symptoms^a	7 (1.2 [0.5, 2.4])	0 (0.0)	0 (0.0)	1 (0.3 [0.0, 1.7])	1 (0.2 [0.0, 1.1])

Notes: ^aOther symptoms reported included discomfort, grittiness, redness, and watering.

Abbreviations: CI, confidence interval; DED, dry eye disease.

Table 5 DED Questionnaires in the Pre- and Post-Index Periods

	Pre-Index n=600	3-Months (± 30 Days) Post-Index n=571	6-Months (± 30 Days) Post-Index n=534	12-Months (± 60 Days) Post-Index n=320
5-Item Dry Eye Questionnaire (DEQ-5) score [0–22]
Patients with documentation of symptom score, n (% [95% CI])	77 (12.8 [10.3, 15.8])	10 (1.8 [0.8, 3.2])	12 (2.2 [1.2, 3.9])	14 (4.4 [2.4, 7.2])
Mean ± SD [median] (95% CI of mean)	14.3 ± 4.2 [15.0] (13.3, 15.2)	9.8 ± 5.8 [9.0] (5.7, 13.9)	7.4 ± 4.8 [6.0] (4.4, 10.4)	6.5 ± 4.2 [6.0] (4.1, 8.9)
Ocular Surface Disease Index (OSDI) score [0–100]
Patients with documentation of symptom score, n (% [95% CI])	54 (9.0 [6.8, 11.6])	6 (1.1 [0.4, 2.3])	6 (1.1 [0.4, 2.4])	8 (2.5 [1.1, 4.9])
Mean ± SD [median] (95% CI of mean)	60.5 ± 24.8 [65.5] (53.8, 67.3)	31.3 ± 17.8 [25.0] (12.6, 50.0)	41.8 ± 23.7 [35.0] (17.0, 66.7)	28.8 ± 17.3 [25.0] (14.3, 43.2)
Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire score [0–28]
Patients with documentation of symptom score, n (% [95% CI])	37 (6.2 [4.4, 8.4])	5 (0.9 [0.3, 2.0])	4 (0.7 [0.2, 1.9])	7 (2.2 [0.9, 4.5])
Mean ± SD [median] (95% CI of mean)	17.5 ± 5.4 [20.0] (15.7, 19.3)	12.2 ± 3.3 [12.0] (8.0, 16.4)	6.8 ± 3.3 [7.0] (1.5, 12.0)	7.7 ± 5.0 [5.0] (3.1, 12.4)
No symptom questionnaire reported, n (% [95% CI])	383 (63.8 [59.8, 67.7])	539 (94.4 [92.2, 96.1])	497 (93.1 [90.6, 95.1])	281 (87.8 [83.7, 91.2])

Abbreviations: CI, confidence interval; DED, dry eye disease; SD, standard deviation.

Table 6 DED Sign Assessments in the Pre- and Post-Index Periods

	Pre-Index n=600	3 Months (± 30 Days) Post-Index n=571	6 Months (± 30 Days) Post-Index n=534	12 Months (± 60 Days) Post-Index n=320
Corneal staining score [0–15]
Patients with documentation of sign assessment, n (% [95% CI])	111 (18.5 [15.5, 21.8])	14 (2.5 [1.3, 4.1])	15 (2.8 [1.6, 4.6])	31 (9.7 [6.7, 13.5])
Mean ± SD [median] (95% CI of mean)	6.5 ± 3.9 [6.0] (5.8, 7.3)	2.7 ± 2.3 [2.0] (1.4, 4.0)	3.0 ± 3.0 [2.0] (1.3, 4.6)	2.0 ± 1.7 [2.0] (1.3, 2.6)
Schirmer score (mm)
Patients with documentation of sign assessment, n (% [95% CI])	82 (13.7 [11.0, 16.7])	5 (0.9 [0.3, 2.0])	7 (1.3 [0.5, 2.7])	17 (5.3 [3.1, 8.4])
Mean ± SD [median] (95% CI of mean)	6.3 ± 10.8 [5.0] (3.9, 8.7)	10.6 ± 1.7 [11.0] (8.5, 12.7)	9.6 ± 2.8 [10.0] (7.0, 12.1)	10.0 ± 3.2 [9.0] (8.4, 11.6)
Tear film break up time (TFBUT)
Patients with documentation of sign assessment, n (% [95% CI])	237 (39.5 [35.6, 43.5])	36 (6.3 [4.5, 8.6])	34 (6.4 [4.4, 8.8])	46 (14.4 [10.7, 18.7])
Mean ± SD [median] (95% CI of mean)	4.8 ± 3.1 [4.0] (4.4, 5.2)	7.3 ± 3.1 [7.5] (6.2, 8.3)	7.8 ± 2.1 [8.0] (7.0, 8.5)	8.0 ± 2.8 [8.0] (7.2, 8.8)
No sign assessment reported, n (% [95% CI])	249 (41.5 [37.5, 45.6])	522 (91.4 [88.8, 93.6])	481 (90.1 [87.2, 92.5])	248 (77.5 [72.5, 82.0])

Abbreviations: CI, confidence interval; DED, dry eye disease; SD, standard deviation; TFBUT, tear film break-up time.