Six and eight weeks injection frequencies of bevacizumab are non-inferior to the current four weeks injection frequency for quality of life in neovascular age-related macular degeneration: a randomized controlled trial

NTR 6126 (Dutch Trial Register) | | Visser (2020) - Six

Visser MS, Amarakoon S, Missotten T, Timman R, Busschbach JJV. Six and eight weeks injection frequencies of bevacizumab are non-inferior to the current four weeks injection frequency for quality of life in neovascular age-related macular degeneration: a randomized controlled trial. Qual Life Res, 2020; 29:3305–3313.

Locations

Single-center study in the Netherlands

Study Period

June 2008 – March 2010

Study Design

Randomized, controlled, open-label, parallel-group trial

Study Population

Characteristic:

Type of AMD:

Wet

AMD Stage:

3 (Late)

Total Sample Size:

191 patients (64 in 4-week, 63 in 6-week, 64 in 8-week groups)

Age:

Randomized, controlled, open-label, parallel-group trial

Sex (Male) n%:

Not reported

Experimental Group

Intervention Therapy:

Exp 1 Bevacizumab 1.25 mg intravitreal injection every 6 weeks Exp 2 Bevacizumab 1.25 mg intravitreal injection every 8 weeks

Dose & Frequency:

Exp 1 Intravitreal bevacizumab injections every 6 weeks for 12 months (9 total injections) Exp 2 Intravitreal bevacizumab injections every 8 weeks for 12 months (7 total injections)

Age (Years):

Exp 1 77.4 ± 6.7 Exp 2 78.1 ± 6.1

Number of Patients:

Exp 1 63 randomized and treated Exp 2 64 randomized and treated

Male N %:

Exp 1 25 (39.7%) Exp 2 21 (32.8%)

Patients Followed Up:

Exp 1 57 (90.5%) Exp 2 53 (82.8%)

Control Group

Intervention Therapy:

Bevacizumab 1.25 mg intravitreal injection every 4 weeks

Dose & Frequency:

Intravitreal bevacizumab injections every 4 weeks for 12 months (13 total injections)

Age (Years):

76.5 ± 6.8

Number of Patients:

64 randomized and treated

Male N %:

18 (28.1%)

Patients Followed Up:

45 (70.3%)

Follow-up Time: 1 year

Outcomes

Durability

Number of Injections The mean number of injections over 12 months:
• 4-week group: 13 injections
• 6-week group: 9 injections
• 8-week group: 7 injections Dropouts
• 4-week group: 29.7%
• 6-week group:9.5%
• Difference: p=0.004
• Patients who dropped out had significantly worse baseline scores than retained patients on the physical component summary of the SF-36:
• t (176) = − 2.95, p=0.004

Vision

Not reported

Other

Quality of Life (QoL) Vision-Related QoL Change in vision-related quality of life (NEI VFQ-39, primary outcome):
• 4-week group: Reference
• 6-week group: +3.68 points (95% CI -0.63 to 8.00)
• 8-week group: +2.15 points (95% CI -2.26 to 6.56)
• Difference: p > 0.05.
• General QoL - Change in general quality of life (SF-36 Physical Component Score):
• 4-week group: Reference
• 6-week group: +0.35 points
• 8-week group: +0.63 points
• Difference: p > 0.05, non-significant
• Change in general quality of life (SF-36 Mental Component Score):
• 4-week group: Reference
• 6-week group: -2.35 points
• 8-week group: -0.54 points
• Difference: p > 0.05, non-significant

Immunognicity

Not reported

Pharmokinetics

Not reported

Anatomic

Not reported

Safety

Study Discontinuation Study discontinuation due to serious AEs:
• 4-week group: 4 (6.3%)
• 6-week group: 0
• 8-week group: 3 (4.7%)
• Difference: p=0.150 Death
• 4-week group: 2 (3.1%)
• 6-week group: 1 (1.6%)
• 8-week group: 0
• Difference: p=0.364

Outcomes

Conclusion

Bevacizumab administered every 6 or 8 weeks was non-inferior to the standard 4-week regimen in terms of quality of life, supporting the use of extended dosing intervals to reduce treatment burden.

Risk of Bias Assessment for Primary Outcome

Randomization Process

High risk
Note: the method of randomization and allocation concealment was not supplied. In addition, significant baseline differences were present for the NEI VFQ-39.

Missing Outcome Data

Low risk
Note: the evidence of the primary outcome analysis was not biased by missingness. “The sensitivity analysis was based on a matched sample (Fig.2).”

Selection of the Reported Results

Low risk Note: Registration with protocol

Deviations from Intended Observations

Some concerns Note: This is an open-label study. There is no information on whether the deviations arose because of the study context. ITT was applied for the primary outcome analysis.

Measurement of the Outcome

Some concerns Note: This is an open-label study. Although it is unlikely, there is no information on whether the QoL assessment was influenced by acknowledging the intervention.

Overall

High risk