Achieving new targets set by the Landmark Studies in Glaucoma

(Cross-references:

  1. Introduction and Target Intra-ocular pressure - Dr. Ravin Das
  2. The role of intra-ocular pressure in glaucoma (Landmark studies in Glaucoma) - Dr. Shabbir Hussain (Slide 1-28)
  3. Implementing what we have learnt - Dr. Major Avinash Mishra (Slide 29-50)
  4. Achieving the targets set by the studies & reaching difficult target pressures - Dr. Rahul Shukla (Slide 51-85)
  5. Lumigan™ the Indian experience (L.E.E.D) - Dr. Shabbir Hussain. (Slide 86-100)


Evolution in the Medical Treatment of Glaucoma in India

Timolol still remains the mainstay because of cost considerations

Pilocarpine gradually getting replaced with Brimonidine after price revisions by major brands

Bimatoprost and Latanoprost still considered "Expensive", however tertiary Institutes and leading Consultants consider them as preferred option to surgery

Beta Blockers Some Limitations

May not achieve target pressures in many patients

Efficacy at night is not proven , hence may not help prevent early morning Spikes.

Not desirable in patients with COPD, Hypertension, Diabetes, Depression , hyperlipidemia etc


LUMIGAN offers superior IOP lowering efficacy

Lumigan offers superior diurnal control

Replace timolol with Lumigan for more IOP reduction


Lumigan efficacy maintained for over 2 years


Lumigan achieves superior IOP reduction to Timolol over 24 hours


Lumigan® demonstrates IOP reduction Vs Latanoprost


Lumigan® demonstrates diurnal control Vs Latanoprost


Lumigan® demonstrates better response rate Vs Latanoprost


Switch Latanoprost non-responder to Lumigan®


Latanoprost Vs Bimatoprost
Bimatoprost Monotherapy Lowers IOP More Effectively Than Latanoprost:

  • A 6-Month Randomized Clinical Trial
  • Multicenter, randomized, investigator-masked trial
  • Adult patients with OHT or chronic glaucoma
  • Treatment groups:
    • Bimatoprost 0.03% qPM, n = 133
    • Latanoprost 0.005% qPM, n = 136
  • Efficacy outcome measures:
    • Mean change from diurnal baseline IOP (1° endpoint)
    • Mean IOP
    • Percentage of patients reaching
      • Specific target pressures
      • 15% and 20% reductions in IOP

Significantly Greater Mean IOP Reductions With Bimatoprost at All Time Points


Bimatoprost Superior to Latanoprost in Primary Endpoint:

  • Mean Change From Baseline IOP
  • Bimatoprost superior to latanoprost at every time point, every visit
  • All differences statistically significant
  • Difference between groups ranged from 1.2 mm Hg to 2.2 mm Hg in diurnal measurements at month 6


Efficacy of Latanoprost Consistent With Reported Literature Values

  • IOP reduction from baseline at 8 AM:
  • 7.1 mm Hg at month 3 and 6.0 mm Hg at month 6
  • Similar to morning IOP reduction measured in other studies:
    • 5.5 mm Hg at month 3 and 6.0 mm Hg at month 6 (Suzuki et al, 2000)
    • 6.2 mm Hg at month 3 (Mishima et al, 1996)

Bimatoprost Also Superior to Latanoprost in All Other Efficacy Measures

  • Mean IOP
    • Significantly lower with bimatoprost at all 3 diurnal measurements at all 4 follow-up visits
  • Percentage of patients reaching specific target pressures
    • Significantly more bimatoprost patients reached low target pressures at all time points at month 6
  • Responder rates
    • Significantly more bimatoprost patients responded to treatment with = 15% and = 20% reductions in IOP

Favorable Safety Outcomes With Both Medications

  • Both drugs were well-tolerated
  • No treatment-related, serious AEs
  • Most common side effects:
    • Hyperemia (bimatoprost 44.4%; latanoprost 20.6%)
    • Eyelash growth (bimatoprost 10.5%; latanoprost 0.0%)
  • Similar rate of discontinuations due to AEs
    • Bimatoprost: 4.5% overall, 2.3% for hyperemia
    • Latanoprost: 3.7% overall, 0.0% for hyperemia
  • Uveitis: 1 patient in latanoprost group; no CME

Bimatoprost Is Consistently Better Than Latanoprost in Lowering IOP

  • 3 published head-to-head trials (1-month, 3-month, 6-month) with IOP follow-up measurements at 24 time points
  • Mean IOP lower with bimatoprost at 22 time points, tied at 2 time points, NEVER lower with latanoprost
  • Mean IOP reductions greater with bimatoprost at 23 time points, tied at 1 time point, NEVER greater with latanoprost


Primary Therapy Comparison: Bimatoprost vs Latanoprost

  • Bimatoprost lowers IOP 1-2 mm Hg more than latanoprost
  • The incidence of hyperemia is approximately twice as high with bimatoprost

Mean Hyperemia Scores With Bimatoprost


Respective Phase III Trial Results: Lower Incidence of Iris Pigmentation Changes With Bimatoprost

  • Increased iris pigmentation reported for 16.1% of patients treated with latanoprost QD for 1 year
  • Increased iris pigmentation reported for only 1.5% of patients treated with bimatoprost QD for 1 year
    • No new reports of iris pigmentation during the second year of bimatoprost treatment

Bimatoprost Reduced Mean IOP in Latanoprost Nonresponders
66% of IOP measurements were < 18 mm Hg on bimatoprost

Most Latanoprost Nonresponders Responded to Bimatoprost

Relative Disadvantages of the Hypotensive Lipids

  • Change in iris pigmentation
  • Eyelash changes
  • Hyperemia
  • Eyelid skin darkening
  • Macular edema in susceptible patients?
  • Exacerbation of uveitis?
  • Exacerbation of herpetic keratitis?
  • Expense

Primary Advantage of the Lipids: Efficacy

  • Excellent, sustained IOP lowering
    • 30%-35% reduction in IOP
    • Greater efficacy than nonselective beta-blockers
      • Effective in the black population, which shows reduced responsiveness to some therapies
    • As monotherapy, lower IOP as effectively as combinations of other drug classes
    • Flat diurnal curves
    • No known tachyphylaxis

     


Other Advantages of Lipids

  • Convenient, once-daily drugs
  • Side effects mostly local
    • Tolerability rather than safety issues
    • Contrasts with serious systemic effects of beta-blockers
  • Low incidence of topical allergies
  • Mechanism of action
    • Enhance outflow to counteract physiological deficit that causes high IOP

Pros and Cons of Bimatoprost as

  • First-Line Therapy
  • Important to maximize efficacy to reduce the risk of progression
  • Bimatoprost lowers IOP better than all other medications
    • Bimatoprost is as great an improvement over latanoprost as latanoprost was to timolol
    • Best chance of getting patient to target IOP
  • Conjunctival hyperemia is more common with bimatoprost than latanoprost

Manage Tolerability to Maximize Efficacy

  • Safety is an issue for the physician, but tolerability will ultimately be decided by the patient
  • The physician can have a large influence on how the patient views tolerability issues
  • Patient education is key:
    • Side effects of treatment should be weighed against possible loss of visual function
    • Side effects that are expected and transient may be best tolerated

Conclusions

  • Hypotensive lipids should be used as first-line therapy for glaucoma
  • Bimatoprost patients are more apt to reach low target pressures with bimatoprost than with latanoprost
  • Many patients who fail to respond adequately to latanoprost may be successfully switched to bimatoprost
  • Tolerability issues with the lipid agents can be addressed with patient education


Goal: Reach Target Pressure

Goal to reach target on initial monotherapy

If target not reached, choices:

  • Switch to more effective primary therapy
  • Add another medication

Benefits of Replacement Therapy

  • Single medication preferable to using multiple medications
    • Safety, tolerability, compliance
  • Eliminate medications no longer effective
    • Reverse therapeutic trial
    • One-eye trial
    • Stop medication weeks prior to next scheduled visit
    • Easy way to determine whether medication still effective

     

Bimatoprost Monotherapy in Patients
Previously on Dual Timolol/Latanoprost