Preservative-free fixed combination of tafluprost 0.0015% and timolol 0.5% in patients with open-angle glaucoma and ocular hypertension: results of an open-label observational study

Figures & data

Table 1 Treatment regimens before and after initiating treatment with the preservative-free fixed combination tafluprost 0.0015%/timolol 0.5%

Type of treatment/active agent	PF TTFC only	PF TTFC adjunctive	Total
	N	N	N
Naïve patients	127	1	128
Monotherapy	578	22	600
Beta-blocker	163	1	164
PGA	338	2	340
CAI	48	12	60
Alpha-2-agonist	28	7	35
Miotic	1	0	1
Nonfixed combinations, two agents	97	23	120
PGA + beta-blocker	55	1	56
PGA + CAI	18	11	29
PGA + alpha-2-agonist	7	9	16
CAI + beta-blocker	8	0	8
CAI + alpha-2-agonist	2	0	2
Alpha-2-agonist + beta-blocker	6	1	7
Alpha-2-agonist + miotic	0	1	1
PGA + miotic	1	0	1
Fixed combinations, two agents	238	4	242
Latanoprost/timolol	47	1	48
Bimatoprost/timolol	80	0	80
Travoprost/timolol	36	0	36
Dorzolamide/timolol	50	1	51
Brinzolamide/timolol	16	0	16
Brimonidine/timolol	6	0	6
Brinzolamide/brimonidine	0	2	2
Miotic/timolol	3	0	3
Nonfixed combinations,	35	32	67
≥3 active agents
≥3 active agents	35	32	67
Total	1,075	82	1,157

Abbreviations: CAI, carbonic anhydrase inhibitor; PGA, prostaglandin analog; PF TTFC, preservative-free tafluprost/timolol fixed combination.

Table 2 Patient characteristics of the patient population (N=1,157) included in the observational study with the preservative-free fixed combination of tafluprost 0.0015% and timolol 0.5%

Parameter	N	%
Gender
Female	688	59.5
Male	469	40.5
Diagnosis
POAG	820	70.9
OH	133	11.5
NTG	81	7.0
PEX	73	6.3
PG	18	1.6
Other	32	2.8
Age
Range	21–104
Mean	67.8
SD	12.8
N/D	n=5

Abbreviations: NTG, normal tension glaucoma; N/D, no data; OH, ocular hypertension; PEX, exfoliative glaucoma; PG, pigmentary glaucoma; POAG, primary open-angle glaucoma; SD, standard deviation.

Figure 1 Reasons for changing medication to preservative-free tafluprost/timolol fixed combination.

Notes: Reporting of multiple reasons for changing medication was possible. Percentages given above the bars based on N=1,029 patients with prior medication irrespective of treatment after change of medication. *Insufficient IOP lowering effect of prior medication(s).
Abbreviation: IOP, intraocular pressure.

Figure 2 IOP at baseline and at final visit in each individual patient irrespective of prior treatment with the preservative-free tafluprost/timolol fixed combination as the only medication at final visit (N=1,075).

Note: IOP was lower at final visit in N=962 (89.5%) eyes (below the line), unchanged in N=55 (5.1%) eyes (on the line) and higher in N=58 (5.4%) eyes (above the line).
Abbreviation: IOP, intraocular pressure.

Figure 3 Decrease of mean IOP (±SD) for different subgroups: Naïve patients (N=127) and patients with prior monotherapy with beta-blockers (N=163), PGAs (N=338), carbonic anhydrase inhibitors (N=48) and alpha-2-agonists (N=28) treated with the preservative-free tafluprost/timolol fixed combination as the only medication at final visit.

Note: *P<0.001.
Abbreviations: CAIs, carbonic anhydrase inhibitors; IOP, intraocular pressure; PGAs, prostaglandin analogs; SD, standard deviation.

Figure 4 Decrease of mean IOP (±SD) in patients with prior monotherapy with different prostaglandin analogs: preserved latanoprost (Lat P; N=113), preservative-free latanoprost (Lat PF; N=59), preserved bimatoprost (Bim P; N=53), preserved travoprost (Tra P; N=40), preserved tafluprost (Taf P; N=34) and preservative-free tafluprost (Taf PF; N=37) treated with preservative-free tafluprost/timolol fixed combination as the only medication at final visit.

Note: *P<0.001.
Abbreviations: IOP, intraocular pressure; SD, standard deviation.

Figure 5 Decrease of mean IOP (±SD) for different subgroups with prior fixed combinations: PGA/timolol (N=163), carbonic anhydrase inhibitor/timolol (N=66) and other fixed combinations (N=9) treated with preservative-free tafluprost/timolol fixed combination as the only medication at final visit.

Notes: *P<0.001, **P=0.007.
Abbreviations: CAI, carbonic anhydrase inhibitor; FC, fixed combination; IOP, intra-ocular pressure; PGA, prostaglandin analog; SD, standard deviation; TIM, timolol.

Figure 6 Decrease of mean IOP (±SD) in patients with prior medical therapy with different preserved prostaglandin analog/timolol fixed combinations: latanoprost/timolol (N=47), bimatoprost/timolol (N=73) and travoprost/timolol (N=36) treated with the preservative-free tafluprost/timolol fixed combination as the only medication at final visit.

Notes: *P<0.001, **P=0.058.
Abbreviations: BIM, bimatoprost; FC, fixed combination; IOP, intraocular pressure; LAT, latanoprost; SD, standard deviation; TRA, travoprost; TIM, timolol.

Figure 7 Decrease of mean IOP (±SD) for different subgroups with prior non-fixed combinations: PGA + beta-blocker (N=55), PGA + carbonic anhydrase inhibitor (N=18) and nonfixed combinations of three different products (N=35) treated with the preservative-free tafluprost/timolol fixed combination as the only medication at final visit.

Notes: *P<0.001, **P=0.007, ***P=0.005.
Abbreviations: CAI, carbonic anhydrase inhibitor; IOP, intraocular pressure; NFC, non-fixed combination; PGA, prostaglandin analog; SD, standard deviation.

Figure 8 Decrease of IOP (mmHg) from different baseline IOP levels in treatment-naïve patients after initiation of medical treatment with the preservative-free tafluprost/timolol fixed combination (N=127).

Note: Numbers in brackets indicate numbers of patients, percentages below bars indicate percentage decrease of IOP for each baseline IOP level.
Abbreviation: IOP, intraocular pressure.

Figure 9 Conjunctival hyperemia at baseline and after initiation of medical therapy with or change of medication in patients treated with the preservative-free tafluprost/timolol fixed combination as the only medication at final visit: All patients with prior medical therapy (N=948), naïve patients (N=127), patients with prior PGA monotherapy (N=338), patients with prior fixed combination PGA/timolol (N=163) and patients with prior non-fixed combinations of a PGA and timolol (N=55).

Abbreviations: BL, baseline; FC, fixed combination; NFC, nonfixed combination; FV, final visit; PGA, prostaglandin analog; TIM, timolol; N/D, no data; ns, not significant.

Figure 10 Conjunctival staining at baseline and after initiation of medical therapy with or change of medication in patients treated with preservative-free tafluprost/timolol fixed combination as the only medication at final visit: All patients with prior medical therapy (N=948), naïve patients (N=127), patients with prior PGA monotherapy (N=338), patients with prior fixed combination PGA/timolol (N=163) and patients with prior nonfixed combination of a PGA and timolol (N=55).

Abbreviations: BL, baseline; FC, fixed combination; NFC, nonfixed combination; FV, final visit; PGA, prostaglandin analog; TIM, timolol; N/D, no data; ns, not significant.

Figure 11 Grading of lid-parallel conjunctival folds at baseline and after initiation of medical therapy with or change of medication in patients treated with preservative-free tafluprost/timolol fixed combination as the only medication at final visit: All patients with prior medical therapy (N=948), naïve patients (N=127), patients with prior PGA monotherapy (N=338), patients with prior fixed combination PGA/timolol (N=163) and patients with prior nonfixed combination of a PGA and timolol (N=55).

Abbreviations: BL, baseline; FC, fixed combination; FV, final visit; NFC, nonfixed combination; PGA, prostaglandin analog; TIM, timolol; N/D, no data; ns, not significant.

Figure 12 Severity of ocular symptoms in patients with prior medical treatment at baseline and after change of medication to the preservative-free tafluprost/timolol fixed combination (N=948).

Abbreviations: BL, baseline; FV, final visit; N/D, no data.

Figure 13 Severity of ocular symptoms in treatment naïve patients at baseline and at final visit after initiation of medical treatment with the preservative-free tafluprost/timolol fixed combination (N=127).

Abbreviations: BL, baseline; FV, final visit; N/D, no data; ns, not significant.

Table 3 Adverse events and terminations of treatment for the overall study population (N=1,157)

Reason for termination of treatment	Patients (N)	%
Lack of efficacy (intraocular pressure)	25	2.2
Adverse events
Systemic adverse events	6	0.5
Asthmatic disease	1	0.1
Beta-blocker contraindication	1	0.1
Hair loss	1	0.1
Hypertonia	1	0.1
Vertigo	1	0.1
Vertigo, palpitation	1	0.1
Systemic and local adverse events	1	0.1
Coughing, breathing issues, irritation	1	0.1
Local adverse events	29	2.5
Hyperemia	3	0.3
Hyperemia, chemosis	1	0.1
Hyperemia, foreign body sensation	1	0.1
Hyperemia, eye pain	1	0.1
Hyperemia, dry eye sensation	1	0.1
Hyperemia, allergy	1	0.1
Hyperemia, irritation	1	0.1
Blepharitis	1	0.1
Burning	6	0.5
Burning, itching	2	0.2
Burning, stinging	1	0.1
Blurred vision, irritation	1	0.1
Dry eye sensation	1	0.1
Dry eye sensation, itching	1	0.1
Dry eye sensation, tired eyes	1	0.1
Eye pain, irritation	1	0.1
Foreign body sensation	1	0.1
Irritation	3	0.3
Tearing, blurred vision	1	0.1
Handling issue unit doses	3	0.3
Compliance	1	0.1
Patient preference	4	0.3
Cost	1	0.1
Unspecified reasons for termination	15	1.3
Total terminations	85	7.3

Note: These also include patients who were treated concomitantly with the preservative-free tafluprost/timolol fixed combination at final visit.