<p>Longitudinal changes in dry eye symptoms and signs following lifitegrast therapy and relationship to tear osmolarity</p>

Abstract

Background This study measured longitudinal changes in dry eye disease (DED) symptoms and signs following lifitegrast therapy and assessed their relationship to tear osmolarity to test the hypothesis that a decline in tear osmolarity is a reliable leading indicator of subsequent improvement in DED symptoms and signs after initiating lifitegrast treatment. Methods This phase IV, prospective, single-arm, open-label, 12-week study enrolled subjects aged ≥18 years with eye dryness score ≥40 (0–100 VAS) and tear osmolarity ≥308 mOsm/L. Subjects were prescribed lifitegrast ophthalmic solution 5%, twice daily in each eye. DED symptoms were assessed via VAS at baseline and 2, 6, and 12 weeks. Signs included tear osmolarity, meibomian gland dysfunction, tear breakup time, and fluorescein corneal staining. In post-hoc analysis, subjects with ≥5 mOsm/L decrease in osmolarity over 12 weeks were Responders. Results Of 26 subjects in the intent-to-treat population, 23 were female; mean age was 67.4 years. Baseline mean±SD eye dryness was 68.7±16.5 and tear osmolarity was 317.8±8.5 mOsm/L. All seven symptoms (dryness, burning, foreign body sensation, pain, photophobia, itching, blurred vision) declined significantly ( P <0.01) from baseline to 6 and 12 weeks. Signs did not change significantly. For 13 Responders, tear osmolarity decreased from baseline to 12 weeks (319.2±8.5 to 300.6±12.3 mOsm/L, P <0.001) and corneal staining trended toward improvement (1.1±0.9 to 0.6±0.7, P =0.136). Among Nonresponders, osmolarity increased from 316.4+8.7 to 329.6+13.9 ( P <0.01) and corneal staining showed no change (1.3±0.8 to 1.0±0.7 at 12 weeks, P =0.293). Conclusions Lifitegrast reduced DED symptoms among subjects with moderate-to-severe disease (severity defined by VAS for eye dryness). Potential reasons that may underlie the dichotomous effect of drug treatment on tear osmolarity are discussed.

TNF-α inhibitor tanfanercept (HBM9036) improves signs and symptoms of dry eye in a phase 2 trial in the controlled adverse environment in China

“…Additionally, this effect was more apparent in subjects who have not used artificial tears (US P2). The proportion of subjects in this study who have used artificial tears was much lower ( n = 5, 5%) compared to subjects in both, the US study and other studies [ 7 , 23 ]. Despite the key differences in subject populations between the two studies (USA and China), the replication of clinically significant efficacy at the primary endpoint signals the robust potential of 0.25% tanfanercept to be highly efficacious for the treatment of DED.…”

Selective Pharmacologic Therapies for Dry Eye Disease Treatment: Efficacy, Tolerability, and Safety Data Review from Preclinical Studies and Pivotal Trials

“…A phase 4, open-label, 12-week study measured longitudinal changes in DED signs and symptoms [ 50 ]. Over 12 weeks of treatment, statistically significant reductions from baseline were observed for all DED symptoms (dryness, burning, foreign body sensation, pain, photophobia, itching, and blurred vision) at week 6 and 12 ( P < 0.010) [ 50 ]. In contrast, no significant changes from baseline in clinical signs were noted at any time point over the 12-week treatment period.…”

The role of Th17 immunity in chronic ocular surface disorders

“…The Lifitegrast ophthalmic solution 5.0% (Xiidra®), approved in the US in 2016, has shown promise in reducing corneal staining and improving DED symptoms across 4 clinical trials [126][127][128][129]. Notably, one study reported that patients with moderate-to-severe DED had significant improvement in their symptoms, but demonstrated no effect on the clinical signs of DED [130]. This contrasts with a recent study showing significant improvements in conjunctival and corneal staining as well as tear film breakup time (TBUT) in patients with moderate-to-severe DED [131].…”