|Year : 2022 | Volume
| Issue : 3 | Page : 227-233
A comparative study of efficacy and safety of alcaftadine 0.25% versus olopatadine hydrochloride 0.2% in allergic conjunctivitis at a tertiary care hospital
Akila Krishnan1, CR Jayanthi2, Sriya Sridhar3
1 Postgraduate, Department of Pharmacology, Bangalore Medical College and Research Institute, Bangalore, Karnataka, India
2 Dean cum Director and Professor, Department of Pharmacology, Bangalore Medical College and Research Institute, Bangalore, Karnataka, India
3 Assistant Professor, Department of Ophthalmology, RRMCH, Former Fellow in Cornea and Refractive Surgeries, Minto Ophthalmic Hospital, Regional Institute of Ophthalmology, BMCRI, Bangalore, Karnataka, India
|Date of Submission||25-Aug-2021|
|Date of Decision||05-Sep-2021|
|Date of Acceptance||08-Sep-2021|
|Date of Web Publication||22-Dec-2022|
Dr. Sriya Sridhar
Assistant Professor, Department of Ophthalmology, RRMCH, Former Fellow in Cornea and Refractive Surgeries, Minto Ophthalmic Hospital, Regional Institute of Ophthalmology, BMCRI, Bangalore, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Ocular itching is the hallmark symptom of allergic conjunctivitis, accompanied by tearing, conjunctival redness, eyelid swelling, and chemosis. Alcaftadine and olopatadine hydrochloride are classified as dual-acting antiallergic agents, used in the treatment of allergic conjunctivitis. Objective: The aim is to compare the efficacy and safety of alcaftadine 0.25% and olopatadine hydrochloride 0.2% eye drops among patients with allergic conjunctivitis. Settings and Design: Ophthalmology outpatient department at Minto Ophthalmic Hospital, Bangalore Medical College and Research Institute, Bengaluru; prospective, randomized, comparative study. Subjects and Methods: This study was conducted among 120 patients suffering from grade 3 Allergic conjunctivitis and efficacy measured in terms of proportion of patients achieving symptomatic relief of allergic ocular signs and symptoms from grade 3 to grade 0 from baseline to 2 weeks, using Total Ocular Symptoms Score (TOSS) and Conjunctival Hyperemia scale. Safety assessed by monitoring treatment-emergent adverse effects. Continuous data assessed by unpaired, paired t-test and repeated measures-ANOVA and categorical data by Chi-square test. P <0.05 was considered statistically significant, whereas < 0.001 as highly significant. Results: Greater proportion of patients achieved symptomatic relief in the Alcaftadine group (98.3%) compared to the olopatadine hydrochloride group (90%) at end of 2 weeks. A significant and faster reduction in TOSS score was observed from baseline to 2 weeks in alcaftadine treated group compared to the olopatadine hydrochloride group (P < 0.05). Adverse events reported were headache, burning sensation, and mild redness in both groups. Conclusion: Alcaftadine 0.25% demonstrated greater efficacy in reducing ocular signs and symptoms of allergic conjunctivitis from baseline to 2 weeks, compared to olopatadine hydrochloride 0.2% with minimal side-effects.
Keywords: Alcaftadine 0.25% eye drops, allergic conjunctivitis, conjunctival hyperemia scale, olopatadine hydrochloride 0.2% eye drops, total ocular symptoms score
|How to cite this article:|
Krishnan A, Jayanthi C R, Sridhar S. A comparative study of efficacy and safety of alcaftadine 0.25% versus olopatadine hydrochloride 0.2% in allergic conjunctivitis at a tertiary care hospital. Kerala J Ophthalmol 2022;34:227-33
|How to cite this URL:|
Krishnan A, Jayanthi C R, Sridhar S. A comparative study of efficacy and safety of alcaftadine 0.25% versus olopatadine hydrochloride 0.2% in allergic conjunctivitis at a tertiary care hospital. Kerala J Ophthalmol [serial online] 2022 [cited 2023 Feb 8];34:227-33. Available from: http://www.kjophthal.com/text.asp?2022/34/3/227/364716
| Introduction|| |
Allergic conjunctivitis affects 40% of the global population. Activation of H1, H2 histamine receptors leads to ocular itching and vasodilatation, respectively.,,, Olopatadine hydrochloride is a selective H1-receptor antagonist; mast-cell stabilizer with additional anti-inflammatory effects, whereas alcaftadine, a dual-acting agent (anti-histaminic, mast-cell stabilizer with anti-inflammatory property), provides relief from ocular itching by inverse agonistic effects on H1, H2, and H4 receptors., Considering the paucity of comparative studies, with regard to efficacy and safety among Indian patients, this study was undertaken. The objective was to compare the reduction in ocular signs and symptoms using the Total Ocular Symptoms Score (TOSS).
| Subjects and Methods|| |
It is a prospective, randomized, comparative study conducted from May 2019 to December 2019, after obtaining Institutional Ethics Committee approval and written informed consent, patients of either sex aged 18–40 years, diagnosed with allergic conjunctivitis with grade 1–3 ocular allergic symptoms were included in the study. Patients not willing for written informed consent, patients with grade 4 severity of ocular allergic symptoms, patients with known hypersensitivity to the study medications or their components (including benzalkonium chloride), intraocular pressure of more than 21 mm Hg in either eye or any type of glaucoma, those on other medications which may interfere with the study like decongestants, prostaglandin derivatives, ocular or systemic nonsteroidal anti-inflammatory drugs and corticosteroids, those having active ocular infection or serious ocular pathological condition, a history of dry eye syndrome, patients who have undergone ocular surgical interventions within the past 3 months, female patients who are pregnant or lactating or considering pregnancy, psychiatric or emotional disturbance in patients which would limit the ability of the patients to comply were excluded.
A total of 120 patients suffering from allergic conjunctivitis were recruited after fulfilling the inclusion and exclusion criteria, allotted into two groups of 60 each and randomized in 1: 1 ratio, to receive either alcaftadine 0.25% eye drops, 1 drop once daily or olopatadine hydrochloride 0.2% eye drops, 1 drop once daily for 14 days. Demographic data, ocular and medical histories, concomitant medications, physical examination, clinical examination including recording of vital signs, ophthalmological examination, and details of drug prescription by the treating Ophthalmologist were recorded in the study pro forma at the baseline visit (visit 1). Follow-up visits were on day 3 (visit 2), day 7 (visit 3) and day 14 (visit 4) after administering the study drugs. A deviation of ± 1 day for the first follow-up and ± 2 days for subsequent follow-up were accepted. At each follow-up visit, data on concomitant medications, ocular symptoms (graded by the patients) and ocular signs (graded by slit-lamp examination by the investigator) and adverse events (AEs) were collected. In case of relapse, the patient was asked to visit OPD on Day 21.
Ocular symptoms and signs were recorded from baseline (Day 1) and adverse effects if any were recorded on follow-up visits (Day 3, 7, 14). The primary efficacy outcome measure was the proportion of patients achieving symptomatic relief of allergic ocular symptoms from grade 3 to grade 0 from baseline to 2 weeks using TOSS score and conjunctival hyperemia as shown in [Table 1] (represents grading of ocular signs and symptoms) and [Table 2] (represents the scale of the assessment of conjunctival hyperemia), respectively, and the secondary outcome was the number and severity of AEs on the follow-up visits.
Sample size calculation:
Sample size is calculated using the formula:
n1 and n2 = sample size for Group 1 and Group 2
such that, N = n1 = n2
ratio r = n1/n2 = 1/1 = 1
Zα = normal deviate at a level of significance = 1.96 for 5% level of significance
Z1-β = normal deviate at 1-β +% power = 0.84 at 80% power
p1 − p2 = Difference in proportion of events in two groups = 0.26
P = Pooled prevalence = (p1 + p2)/2 = 0.63
Considering 10% drop out rate,
N1 = Total sample size including drop outs
N = Total sample size
q = anticipated drop outs = 0.1 (10%)
A sample size of 120 was taken for better validation of results.
The data collected were analyzed statistically using descriptive statistics, namely mean, standard deviation and proportion/percentage wherever applicable. Continuous data were assessed by the Unpaired t-test used between the two groups and RM-ANOVA within the group and categorical data were assessed using Chi-square test using VassarStats statistical computation. P <0.05 was considered statistically significant, whereas < 0.001 was highly significant.
| Results|| |
120 patients diagnosed with allergic conjunctivitis with grade 3 ocular allergic symptoms who met inclusion criteria were enrolled in the study. [Table 3] represents the baseline demographic profile of the patients included in the study. There was no statistical difference in age and gender in both the groups (P = 1.00; P = 0.74, respectively). Both the treatment groups were matched with respect to baseline demographic characteristics.
|Table 3: Baseline demographic characteristics (60 patients in each group)|
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Patients with a mean age of 27.9 ± 7.7 years in alcaftadine group and 26.7 ± 5.38 years in olopatadine group. There were 39 (65%) male and 21 (35%) female in alcaftadine group and 35 (58.3%) male and 25 (41.7%) female patients in the olopatadine group.
The ocular symptoms and signs assessed using TOSS score were itching (100%), tearing (83.3%), redness (71.6%), and swelling (19%) of the conjunctiva.
[Figure 1] shows the TOSS score from visit 1 (baseline) to visit 4 in both groups. [Table 4] and [Figure 2] represent the number of patients with their Total Ocular Symptom Score at different visits from baseline visit 1 (Day 1) to visit 4 (Day 14).
|Figure 1: TOSS Score from visit 1 (baseline) to visit 4 in both the groups|
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|Table 4: Number of patients with their total ocular symptoms score from baseline visit 1 to visit 4|
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Both the groups showed a significant improvement in TOSS scores from baseline to 14 days. The total ocular symptom score showed consistent decrease in subsequent visits in both the study groups and it was statistically significant from baseline to 14th day (P = 0.03). [Table 5] shows the TOSS score at different visits.
Conjunctival Hyperemia grading from baseline to day 14 is represented in [Table 6] and [Figure 3]. Conjunctival hyperemia was significantly reduced in both the treatment groups. There is no statistical significance between the groups while assessing the conjunctival hyperemia scale in all the visits.
|Table 6: Conjunctival Hyperemia Scale from visit 1 (baseline) to visit 4 in both the groups|
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|Figure 3: Conjunctival hyperemia grading from baseline (Day 1) to visit-4 (Day 14)|
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Within the individual group of alcaftadine 0.25% [Table 7] and olopatadine hydrochloride 0.2% [Table 8], the TOSS score and conjunctival hyperemia scale were statistically highly significant (P < 0.001) from baseline to follow-up visit 4. The number of patients in alcaftadine group who achieved faster symptomatic relief were higher, compared to olopatadine hydrochloride 0.2% group.
|Table 7: Total ocular symptoms score and Conjunctival Hyperemia Scale (within alcaftadine 0.25% group)|
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|Table 8: Total ocular symptoms score and Conjunctival Hyperemia Scale (within olopatadine hydrochloride 0.2% group)|
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| Safety parameter|| |
Adverse drug reactions (ADRs) encountered in our study were headache, burning sensation, dizziness, and mild redness in the conjunctiva. All four ADRs were mild, self-limiting and did not require the discontinuation of therapy. [Table 9] represents the ADRs in both groups.
| Discussion|| |
The conjunctiva of the eye is continually exposed to a variety of airborne antigens that can lead to inflammation, often termed allergic conjunctivitis. Allergic conjunctivitis is an ocular surface inflammatory disease that is predominantly IgE-mediated Type I hypersensitivity reaction where allergen binds to specific IgE molecules, triggers mast cell degranulation and subsequent increase in histamine release leading to activation of both H1 and H2 types of histamine receptors leading to ocular itching and vasodilatation associated with ocular redness, eyelid swelling, and chemosis, respectively.
Pharmacological treatment of allergic conjunctivitis includes H1 receptor blockage, mast cell stabilization, and blocking of cytokine production and prostaglandin formation. Topical antihistamines are first-line agents in the treatment of allergic conjunctivitis. Currently, alcaftadine 0.25% and olopatadine hydrochloride 0.2% are the only approved once-daily, dual-acting anti-allergic agents for allergic conjunctivitis which includes inhibition of histamine receptor activation directly and reduction of allergic responses by stabilizing mast cells indirectly.,
Olopatadine hydrochloride is a selective histamine H1-receptor antagonist and mast-cell stabilizer with additional anti-inflammatory effects such as suppression of interleukins 6 and 8 production by inhibiting histamine-related signaling pathways. Alcaftadine is an anti-allergic agent that provides relief from ocular itching by inverse agonistic effects on H1, H2 and H4 histamine receptors in the early phase and also stabilizes mast cells by inhibiting the release of mediators such as cytokines and lipid mediators in the late phase of ocular allergic response in allergic conjunctivitis. Furthermore, it decreases chemotaxis and inhibits eosinophil activation and thereby exerts anti-inflammatory properties.,
In the present study, the mean age was comparable and matched in both groups. The majority of patients enrolled in our study were 26.7 ± 5.38 years in olopatadine group and 27.9 ± 7.7 years in alcaftadine group. There were 35 (58.3%) male and 25 (41.7%) female patients in the olopatadine group and 39 (65%) males and 21 (35%) females in alcaftadine group, suggesting a slight male preponderance, that was also observed in a study by Nakatani et al., which could be due to the socioeconomic status of the patients visiting our Government hospital and the social set up where the majority of the females do not report to the hospital.
The present study was conducted to compare the efficacy and safety of dual-acting, once daily, topical antihistamine solutions, alcaftadine 0.25% versus olopatadine hydrochloride 0.2% eye drops in the treatment of allergic conjunctivitis. Our findings of the study showed greater reduction in TOSS (Total Ocular Symptom Score) from baseline to 2 weeks in alcaftadine group compared to olopatadine hydrochloride group (statistically significant, P < 0.05*). Similarly, the conjunctival hyperemia scale also showed larger reduction within the group of alcaftadine and olopatadine treated patients (P < 0.001) from baseline (Day 1) to follow-up visit (Day 14).
The study confirmed the treatment outcome differences between alcaftadine 0.25% and olopatadine hydrochloride 0.2% eye drops. Alcaftadine 0.25% treated group achieved faster symptomatic relief of allergic ocular symptoms from grade 3 to grade 0, using TOSS score at visit 2 (Day 3) and visit 3 (Day 7) than olopatadine hydrochloride 0.2% group. There was a significant reduction in ocular symptoms and signs at the end of the study (Day 14/visit 4) in the alcaftadine group than olopatadine hydrochloride group. The common adverse effects in both groups were headache, burning sensation, and mild redness.
A study by Meena and Gupta, showed that alcaftadine 0.25% ophthalmic solution provided greater symptomatic relief of ocular itching postadministration with a similar safety profile, compared to olopatadine hydrochloride 0.2%. It also mentioned that there were significantly lower mean ocular itch scores in alcaftadine 0.25% treated patients than olopatadine hydrochloride 0.2% group at the 2nd and 3rd follow-ups. The study also confirmed the difference in treatment outcomes between alcaftadine 0.25% and olopatadine 0.2% in preventing signs and symptoms of allergic conjunctivitis on day 3 and day 7 of post-treatment instillation. In the present study, alcaftadine 0.25% showed a statistically significant reduction in TOSS score on Day 14 (visit 4), compared to olopatadine group.
A study by Greiner et al. showed that alcaftadine 0.25% and olopatadine 0.2% had significantly lower mean scores of ocular itching and conjunctival redness compared to placebo at visits 3 and 4. Furthermore, alcaftadine 0.25% was found to be effective and superior over placebo, by reducing ocular symptoms and signs at 15 min and 16 h post instillation suggesting the rapid onset of action and substantial duration of action. Headache was one of the AEs observed in the present study was similar to the study by Greiner et al.
A study by Singh et al. mentioned that Alcaftadine showed marginal superiority in efficacy of reducing ocular itching and conjunctival redness score and found equally safe when compared to olopatadine group.
A study by Nakatani et al., revealed that alcaftadine 0.25% dosed 8 h before allergen challenge was found to be effective or superior in preventing ocular signs and symptoms of Japanese cedar pollen-induced allergic conjunctivitis, compared to olopatadine 0.2% ophthalmic solution (challenged 4 h postdose). The results of the study showed statistical significance in reduction of ocular itching score and conjunctival hyperemia scale in alcaftadine 0.25% group compared to olopatadine 0.2% group. Furthermore, the age and gender of patients enrolled in our study were similar to the study by Nakatani et al.
A study by Ackerman et al., showed differences in relief of itch between alcaftadine 0.25% and olopatadine 0.2% ophthalmic solutions, at the earliest time point measured postconjunctival allergen challenge (CAC) (3 min) and effective in preventing ocular itching at 16-and 24-h postinstillation in a CAC. Furthermore, it stated that alcaftadine group was only active treatment that provided statistical significance in relief of chemosis post 24 h instillation. The current study showed patients achieved faster relief of itching, redness, tearing and chemosis of the conjunctiva at day 14 (follow-up visit 4) more in the alcaftadine group compared to the olopatadine hydrochloride group.
In pooled analysis of two multicenter, randomized clinical trials, done by McLaurin et al., revealed that alcaftadine and olopatadine hydrochloride was superior to placebo at relieving ocular itching alcaftadine 0.25% ophthalmic solution provided greater relief at 16 h postadministration and significantly lower mean itch score at 3 min post CAC with similar safety profile, compared to olopatadine hydrochloride 0.2%
A study on the conjunctival epithelium and eosinophil recruitment in a murine model with allergic conjunctivitis by Ono and Lane, mentioned that alcaftadine significantly inhibited eosinophil recruitment by a broad spectrum of H1, H2, and H4 histamine receptors antagonism and have a protective effect on epithelial tight junction protein expression in the conjunctiva, compared to olopatadine hydrochloride treated group. It also demonstrated the ability to protect epithelial tight junction protein markers from allergic inflammation-based degradation, whereas olopatadine failed to protect from degradation ZO-1 junctional protein.
The present study shows that alcaftadine 0.25% is superior in efficacy and safety when compared to olopatadine hydrochloride 0.2% in the treatment of allergic conjunctivitis. This is a prospective, randomized study design and the use of standard validated tools such as TOSS score and conjunctival hyperemia scale for assessing the efficacy of treatments has added strength to the study.
The study was limited by its relatively smaller sample size. Therefore, further studies with larger sample size are required to evaluate the efficacy and safety of alcaftadine 0.25% versus olopatadine 0.2% in the treatment of allergic conjunctivitis.
| Conclusion|| |
In allergic conjunctivitis, both alcaftadine 0.25% and olopatadine hydrochloride 0.2% were found effective in relieving ocular signs and symptoms, but alcaftadine 0.25% was found to be superior in terms of efficacy, compared to olopatadine hydrochloride 0.2% with minimal side-effects.
The corresponding author would like to thank Dr Bhavyadharshini M., MD Senior Resident, Department of Pharmacology, for writing and editorial assistance
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]