Efficacy of preserved Tafluprost 0.0015% in lowering intraocular pressure

Abstract

Objective:

To investigate the intraocular pressure (IOP) lowering effect of topical preserved tafluprost 0.0015% in a tertiary hospital setting in India.

Methods:

This is a retrospective chart review of patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) attending regular outpatient visits in December 2019 and January 2021, and treated with topical preserved tafluprost 0.0015%. Based on their medication history, patients were divided into two groups, the “treatment naïve” group and the “switched” group, which included patients switched to tafluprost monotherapy after treatment with at least one prior drug.

Results:

The mean IOP of the study population reduced significantly from baseline level by 20.6% and 25.5% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The mean IOP in patients with only OHT reduced significantly from baseline level by 21% and 26% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The mean IOP in patients with POAG reduced significantly from baseline level by 19% and 24% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The baseline IOP ± SD in POAG treatment naïve patients was 25.3 ± 0.3 mmHg, which reduced significantly by 24% and 28% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The baseline IOP ± SD in POAG switched patients was 24.3 ± 0.1 mmHg, which reduced significantly by 18% and 22% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). In the POAG switch group, the percent reduction in IOP at 3 months after preserved tafluprost 0.0015% treatment was 23% with timolol as first line, 22% with bimatoprost as first line, 20% with latanoprost as first line, and 19% with travoprost as first line (P < 0.001 for all).

Conclusions:

We show significant IOP reduction with preserved tafluprost 0.0015% in a real-world setting. As first-line monotherapy in patients with OHT and in POAG–naïve patients, preserved tafluprost 0.0015% significantly reduced IOP at 3 months. Even as second-line therapy in nonresponders (POAG-Switched) to various drugs (same class [PGAs] versus different class), treatment with preserved tafluprost 0.0015% resulted in significant IOP reduction at 3 months.

Glaucoma is the one of the leading causes of blindness across the world, and the global prevalence of glaucoma is projected to be 111.8 million in 2040.[1] India has approximately one fifth of global glaucoma cases.[2] An approximate 11.2 million persons aged 40 years and older in India are suspected to have glaucoma.[3] A study from India reported glaucoma in 2.7% of rural and 3.23% of urban population.[4]

The various types of glaucoma seen in India are primary open angle glaucoma (POAG), primary angle closure disease (PACD), normal tension glaucoma, and secondary glaucoma.[3,4,5] The Singapore Indian study reported age-standardized prevalence of POAG, PGCC, and secondary glaucoma was 1.25%, 0.12%, and 0.55%, respectively.[6] Another community-based study recently reported prevalence of POAG, PGCC, normotensive glaucoma, and secondary glaucoma as 1.3%, 1.2%, 1.2%, and 0.9%, respectively.[5] A tertiary care community program for primary glaucoma found POAG in 54.78% cases and narrow-angle glaucoma in 45.22% cases.[7]

Elevated intraocular pressure (IOP) is the only modifiable risk factors associated with the progression of glaucoma.[8,9] Persistent elevated IOP in glaucoma is associated with irreversible progressive optic nerve damage and associated visual field loss.[10] IOP reductions are the only effective evidence-based treatment that delays the progress of optic nerve damage in glaucoma.[11,12,13,14]

Several classes of topical IOP-lowering medications, in mono- or combination therapies, remain the mainstay of glaucoma therapy. These include beta blockers: timolol, betaxolol, levobunolol; prostaglandin analogs (PGAs): tafluprost, latanoprost, bimatoprost [prostamide], and travoprost; carbonic anhydrase inhibitors: dorzolamide, acetazolamide; adrenergic agonist: epinephrine, dipivefrin; Rho kinase inhibitors; cholineric agents: pilocarpine, carbachol, etc.; and fixed combination drops (e.g., tafluprost + timolol).[10,13,14,15,16,17]

Patients are more likely to adhere to topical medications with strong IOP-lowering effect, good topical and systemic tolerance, and ease of use such as once daily dosing.[18,19,20,21]

Prostaglandin analogs (PGAs) and beta-receptor blocker (typically timolol 0.5%) are most commonly recommended monotherapies.[14,18,21] However, PGA are preferred over beta-blockers due to their higher IOP reduction and overall safety.[14,20,21]

Tafluprost is a prostaglandin F2α analog and its prostanoid FP-receptor affinity is 12 times higher than that of latanoprost.[22,23,24,25] The IOP lowering effect of tafluprost is rapid (seen 2–4 hours after application) and occurs mainly as a result of increased uveoscleral outflow.[22] The maximum IOP lowering effect of once-daily tafluprost ophthalmic solution 0.0015% is seen on Day 7 of application in patients with POAG or ocular hypertension (OHT).[26] After seven days of treatment, tafluprost was shown to have a significantly greater 24-hour IOP lowering effective than latanoprost (P = 0.007).[25] Additionally, microcirculation of optic nerve head is preserved for three years with tafluprost but decreases with latanoprost.[27] Several prospective, randomized clinical trials have demonstrated that tafluprost 0.0015% is efficacious and safe in patients with POAG and OHT.[23,28,29,30] However, there is paucity of tafluprost IOP lowering data from clinical and real-world setting from India. To the best of our knowledge, real-world tafluprost IOP lowering data from India is lacking.

Hence, the current study retrospective chart review study was undertaken at a tertiary hospital in India to assess the IOP-lowering effect of tafluprost 0.0015%.

Material and Methods

Study design and study population

This is a retrospective chart review conducted at an outpatient clinic in a tertiary hospital in India and included patients with POAG or OHT attending regular outpatient visits between December 2019 and January 2021. Based on their medication history, patients were divided into two groups (for the purpose of analysis), the “treatment naïve” group that included patients who had no previous treatment for glaucoma (ocular or systemic); and the “switched” group that included patients switched to tafluprost monotherapy after treatment with at least one prior drug. The reason for switching was due to not achieving desired target IOP and/or significant ocular surface disease in prior treatment. All the patients received tafluprost 0.0015% preserved with benzalkonium chloride (BAK-C12) 0.001 % as part of their regular care. BAK-C12 preserved Tafluprost was found to be safe and free of ocular side effects in the treatment of POAG and OHT.[31,32,33,34]

IOP was routinely measured at baseline (before starting treatment with preserved tafluprost 0.0015%) and at each consecutive visit by the treating physician with Goldman applanation tonometer. The patients also underwent full glaucoma screening at the first visit, which included Humphrey visual field assessment, central corneal thickness, gonioscopy, and optic disc evaluation. IOP >21 mmHg on two or more hospital visits 30 days apart was considered as OHT, with 360 degrees open angles on gonioscopy. IOP >21 mmHg on two or more hospital visits 30 days apart with 360 degrees open angles on gonioscopy, optic disc cupping of 0.6 in either eye, or a difference of 0.2 between the two eyes, with or without RNFL defects, and/or corresponding visual field (VF) loss was considered as POAG, if no other secondary known causes of glaucoma was identified. Data collection from retrospective chart review covered patient demographics, diagnosis, prior/current medication, and IOP at baseline, one month and 3 months postinitiation of tafluprost 0.0015%. Data were collected and de-identified in accordance with the International Conference on Harmonization Guidelines for Good Clinical Practice.

Inclusion/exclusion criteria

Male or female; 18 years and older; and patients with raised IOP who were eligible for treatment with preserved tafluprost 0.0015% in one or both eyes were included in the analysis. Data were collected for patients who had a minimum follow-up of three months after starting preserved tafluprost. Patients with incomplete medical record and data were excluded from the study. Additionally, the following patients were also excluded from the analysis: patients with known allergy or hypersensitivity to preserved tafluprost 0.0015%; patients whose Humphrey visual fields analysis could not be performed due to poor visual acuity; patients with inadequate media clarity or ocular inflammation; patients who had undergone vitrectomy; and patients with corneal abnormality or any condition preventing reliable applanation tonometry results.

Study endpoints

The main outcome measure was the mean IOP change at Month 3.

Statistical analysis

Descriptive statistics along with t-test from sigma plot SPSS was used to determine the significance of association of the preserved tafluprost 0.0015 with reduction in IOP between groups (only OHT and POAG; within POAG group: treatment naïve and switched). In the POAG switched group, IOP lowering effect of preserved tafluprost 0.0015% was analyzed for each first-line treatment given.

Results

Baseline characteristics

Data were collected from 176 eyes of 88 consecutive patients (50 males; 38 females, with raised IOP who were followed up for at least three months after initiation of treatment with preserved tafluprost 0.0015%. The mean age ± standard deviation (SD of the patients was 49.6 ± 4.9 years. OHT was diagnosed in 52 eyes while 124 eyes had POAG [Table 1]. Of the eyes with POAG, 16 were treatment naïve and 108 had switched to preserved tafluprost 0.0015% [Table 2]. In the POAG switch group, treatment was most initiated with latanoprost (n = 34), followed by timolol (n = 24), bimatoprost (n = 22), and travoprost (n = 12) [Table 3].

Table 1.

Ocular hypertension versus POAG analysis

Group	Total eye	IOP (mm Hg)
		Baseline (±SD)	1 month (±SD)	3 months (±SD)
Only OHT	52	25±0.2	19.7±0.3	18.5±0.2
% reduction (P)			21 (<0.001)	26 (<0.001)
POAG	124	24.5±0.1	19.8±0.2	18.6±0.2
% reduction (P)			19 (<0.001)	24 (<0.001)
Total	176	24.8±0.2	19.7±0.3	18.5±0.2
% reduction (P)			20.6 (<0.001)	25.5 (<0.001)

Table 2.

Subgroup analysis in POAG group

Group	Total eye	IOP (mm Hg)
		Baseline (±SD)	1 month (±SD)	3 months (±SD)
POAG-Naïve	16	25.3±0.3	19.2±0.4	18.3±0.4
% reduction (P)			24 (<0.001)	28 (<0.001)
POAG-Switched	108	24.3±0.1	19.8±0.2	19.1±0.2
% reduction (P)			18 (<0.001)	22 (<0.001)

Table 3.

First-line treatment-wise analysis in POAG-Switched

Group	Total eye	IOP (mm Hg)
		Baseline (±SD)	1 month (±SD)	3 months (±SD)
POAG-Bimatoprost (prostaglandin analogue)	22	24.2±0.3	19.7±0.4	18.8±0.4
% reduction (P)			18 (<0.001)	22 (<0.001)
POAG-Latanoprost (prostaglandin analogue)	34	24.1±0.2	19.8±0.4	19.2±0.4
% reduction (P)			18 (<0.001)	20 (<0.001)
POAG-Timolol (beta blocker)	24	25.0±0.3	20.5±0.5	19.3±0.4
% reduction (P)			18 (<0.001)	23 (<0.001)
POAG-Travoprost (prostaglandin analogue)	12	23.9±0.3	19.7±0.4	19.3±0.5
% reduction (P)			18 (<0.001)	19 (<0.001)

Treatment outcomes

The mean IOP of the study population reduced significantly from baseline level by 20.6% and 25.5% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both) [Table 1]. The mean IOP in patients with only OHT reduced significantly from baseline level by 21% and 26% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The mean IOP in patients with POAG reduced significantly from baseline level by 19% and 24% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both).

The baseline IOP ± SD in POAG treatment naïve patients was 25.3 ± 0.3 mmHg, which reduced significantly by 24% and 28% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The baseline IOP ± SD in POAG switched patients was 24.3 ± 0.1 mmHg, which reduced significantly by 18% and 22% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both) [Table 2].

In the POAG switch group, the percent reduction in IOP at 3 months after preserved tafluprost 0.0015% treatment was 23% with timolol as first line, 22% with bimatoprost as first line, 20% with latanoprost as first line, and 19% with travoprost as first line (P < 0.001 for all) [Table 3, Fig. 1].

Figure 1.

First line treatment wise analysis of IOP lowering effect in POAG-Switched

Safety

The majority of patients did not experience any adverse signs or symptoms. Eye redness was the most common adverse symptom reported, and conjunctival hyperemia was the most commonly noted adverse event. No patients discontinued treatment due to adverse symptoms or signs during the reviewed period. The overall incidence of adverse effects was similar to those mentioned in global evidences of the safety of tafluprost 0.0015% in patients with POAG and OHT as shown in prospective, randomized clinical trials.[23,26,30,35]

Discussion

This retrospective chart review capturing real-word data from a tertiary care hospital in India showed a significant reduction in IOP in all patients after 3 months of treatment with preserved tafluprost 0.0015%. The IOP lowering effect was seen both in patients with OHT and in those with POAG. Within the POAG group, IOP lowering effect was seen in both treatment naïve patients and in the patients switched to preserved tafluprost 0.0015%. Among the patients with POAG switched to tafluprost, patients were initially treated with PGAs mainly. Of the PGAs, latanoprost was the most common treatment given followed by bimatoprost. Other than PGAs, timolol, a beta blocker, was the most common initial treatment given.

Our results were similar to other real-world studies from Asia. A prospective observational Japanese study (N = 4,180) found a significant decrease in IOP by 4.3 ± 5.2 mmHg in patients with POAG after two months of treatment with preserved tafluprost 0.0015%.[24] Within the POAG group, the treatment naïve monotherapy group saw a significant IOP reduction by 4.3 ± 4.0 mmHg, whereas the switch group reported a significant reduction of 1.9 ± 3.5 mmHg after two months of treatment with preserved tafluprost 0.0015%.[24] Our results were also similar to a retrospective analysis of glaucoma, and OHT patients from Philippines receiving tafluprost 0.0015% (BAK 0.001% preserved) with a minimum follow-up of three months showed a significant reduction in IOP by 26.37% (P < 0.001).[20] Subgroup analysis of 203 treatment naïve group demonstrated significant mean IOP reduction from baseline to month 3 by 31.24% (P < 0.001). The subgroup analysis of 73 patients for whom the primary therapy was replaced with tafluprost showed a significant post-switch 6.31% reduction in IOP from baseline d (P = 0.007). Latanoprost was the most common drug used before the switch, followed by bimatoprost.[20] Among POAG switched patients in the Japanese study, latanoprost was the most common previous PGA used followed by travoprost.[24] Significant IOP reductions by 1.5 ± 3.4 mmHg and 1.3 ± 3.7 mmHg were observed in switching from latanoprost and travoprost, respectively. In our study, bimatoprost was the second most common PGA after latanoprost. However, as seen the Japanese study, there was a significant IOP reduction (P < 0.001 for all) in all patients who failed on any previous PGAs (latanoprost, bimatoprost, and travoprost). The Japanese and Philippino studies evaluated tafluprost as an add-on therapy and reported significant IOP reductions as compared to monotherapy; however, in our study, no patient received tafluprost as an add-on therapy.

In our study too, though significant in both groups, the IOP reduction three months after treatment was greater in the treatment naïve than in switch group (by 28% versus 22%; P < 0.001 for both). Also, as seen in the Japanese and Philippines study, IOP reduction was higher in patients with higher baseline IOP; the POAG-naïve group had higher baseline IOP (25.3 ± 0.3 mmHg) and higher IOP reduction (to 18.3 ± 0.4 mmHg) that POAG switch group (from 24.3 ± 0.1 mm Hg to 19.1 ± 0.2 m Hg). Table 4 shows the comparative efficacy and safety of tafluprost from real-world studies from Asia.

Table 4.

Comparative efficacy and safety of tafluprost from real-world studies from Asia

Country/Study type	Population size	Duration of treatment	IOP lowering	IOP lowering as per previous drug used	IOP lowering other ophthalmic conditions	ADRs
Japan (tafluprost ophthalmic solution 0.0015%)[24]; real-world prospective observational	n=4180	2 months	POAG: -4.3±5.2 mmHg*	PGA: latanoprost (predominant): 1.5±3.4 mmHg travoprost: 1.3±3.7 mmHg	NTG: 2.4±2.5 mmHg*	7.7%
			OH: -5.3±4.8 mmHg*		Primary angle closure glaucoma: 3.6±5.3 mmHg*
			Treatment naïve: -4.3±4.0 mmHg*		Other types of glaucoma: 5.6±7.1 mmHg*
			Switched: -1.9±3.5 mmHg*
Philippines (tafluprost 0.0015% (BAK 0.001% preserved)[20]; real-world retrospective	n=177 (329 eyes)	≥3 months	Mean IOP change: −6.18 mmHg IOP reduction: −26.37% (P<0.001) Significant reduction for POAG/OH Treatment naïve: −8.34 mmHg*	Latanoprost was premedication in 57.5% of cases and Bimatoprost in 27.4% of cases Switched group −1.00 mmHg or −6.31% decrease	PAC glaucoma post-laser iridotomy, PAC post-laser iridotomy, secondary glaucoma, NTG	15% Conjunctival hyperemia
Our study (India) (preserved tafluprost 0.0015%); real-world retrospective	n=88 (176 eyes)	≥3 months	Reduction by 25.5%* POAG: reduction by 24%* OH: reduction by 26%* Treatment naïve: by 28%* Switched: by 22%	latanoprost (n=34), followed by timolol (n=24), bimatoprost (n=22) and travoprost (n=12) Reduction: 23% with timolol, 22% with bimatoprost, 20% with latanoprost and 19% with travoprost	NA	No major ADRs

*Significant reduction. BAK, benzalkonium chloride; OH, ocular hypertension; PAC, primary angle-closure; POAG, primary open-angle glaucoma; NA, not applicable; NTG, normal tension glaucoma

The efficacy and safety of tafluprost has also been confirmed in many clinical trials. In a Japanese study, (N = 30) patients who received latanoprost for 4 weeks were randomly assigned to latanoprost or tafluprost for 12 weeks and then switched to the other drug after 12 weeks.[36] The two groups (latanoprost to tafluprost switch and tafluprost to latanoprost switch) did not differ significantly in their IOP lowering effect. In our study, patients switched from latanoprost to tafluprost had 18% and 20% reduction in IOP at 1 month and 3 months, respectively (P < 0.001 for both). Keating (2016) reported IOP lowering benefit of tafluprost from several Asian studies in patients switched to the drug from latanoprost.[32]

The beneficial safety profile of tafluprost compared to other PAGs has been extensive studied in both treatment naïve patients and in those switched to tafluprost from other drugs. A study compared the ocular surface status of patients with POAG or OHT switched from latanoprost to tafluprost. Treatment with preserved tafluprost resulted in significant improvement in dryness (tear break-up time; TBUT), subjective symptoms, and hyperemia score (P < 0.05 for all).[31] A clinical study assessed the efficacy and safety of switching patients with glaucoma treated with latanoprost or travoprost to BAK-C12-preserved tafluprost.[37] After the switch to tafluprost, there was no change in IOP lowering effect, but the ocular scores improved significantly (P < 0.0001).

In a prospective randomized study, 30 patients with PAOG were switched from any of the following preserved PGAs (latanoprost, bimatoprost, travoprost) to preserved tafluprost. The TBUT was significantly lower after switching to tafluprost (P = 0.002).[38]

A systematic review and network meta-analysis data for POAG or OHT treatment was used to analyze patient preference for topical PAGs using the quality-adjusted life-years (QALY) 20-year model. The analysis showed that tafluprost conferred similar QALY gain as latanoprost (1.99 vs. 2.00 QALY gain equivalent to 17.9% vs. 17.8% quality-of-life gain). Tafluprost was found to be better than travoprost (l. 92 QALY gain) and timolol (1.42 QALY gain), which was equivalent to 17.2% and 12.8% quality-of-life gain, respectively.[39]

The improvement in ocular scores observed in the above studies is important in correlation with improved patient adherence, which in turn improves efficacy of treatment. Similarly, in our study, treatment with tafluprost was found to be safe and devoid of any serious side effects. Thus, tafluprost provides a balance between efficacy and safety required for effective treatment of POAG and OHT.

The European Glaucoma Society 2020 Guidelines recommend that target IOP should be decided based on several factors including stage of glaucoma, IOP level before treatment, and side effects of the prescribed treatment.[14] The guidelines recommend that normal IOP should be less than 21 mmHG.[14] In our study, all patients with POAG and OHT with mean baseline (SD) IOP of 24.8 ± 0.2 achieved an IOP level of <21 mmHg with tafluprost monotherapy (18.3 ± 0.4 mm Hg) and after switching to tafluprost from another therapy (19.1 ± 0.2 mmHg). Side effects were mild and did not require dose adjustments.

Strengths and limitations of the study

Our study has several limitations. The study is limited by its retrospective study design and by the fact that the efficacy and safety of tafluprost was not assessed against a comparator. Furthermore, the relatively short follow-up may not have been enough to capture the complete clinical course seen in real-world setting. However, the study adds to the clinical data on IOP-lowering efficacy of tafluprost 0.0015% in real-world setting, in both treatment naïve and in switched group. Also, to the best of our knowledge, this is the first study from India, reporting tafluprost 0.0015% IOP lowering data in real-world setting.

Conclusion

We present retrospective chart review of patients with OHT or POAG who had significant IOP reduction with preserved tafluprost 0.0015% in a real-world setting. As first-line monotherapy, preserved tafluprost 0.0015% significantly reduced IOP at 3 months, in patients with OHT and in POAG-treatment naïve patients. Even as second-line therapy in nonresponders (POAG-Switched) to various drugs (same class [PGAs] versus different class), treatment with preserved tafluprost 0.0015% resulted in significant IOP reduction at 3 months.

Ethics compliance

This was a retrospective chart review study, hence exempt from EC/IRB approval.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.