Table_1_Precision in treatment evaluation: importance of minimal clinically important differences (MCIDs) of outcome measures for autoimmune blistering diseases.docx

Autoimmune blistering diseases (AIBDs) comprise a group of rare conditions marked by autoantibodies that specifically target intercellular adhesion molecules. Despite the progress made in comprehending the disease and the increasing number of treatment options available, there is still no definitive cure for AIBDs such as pemphigus, and it continues to have a devastating impact on those affected. The challenges in achieving new approved therapies for AIBDs are complex and multifaceted. One significant obstacle was the prior lack of validated and standardized outcome measures, which are crucial for ensuring precise comparisons between new and traditional therapies. This gap in knowledge has prompted the development of minimal clinically important differences (MCIDs), which enable efficient and reliable comparison of therapeutic outcomes between trials. MCID is defined as the minimum difference in an outcome measure that indicates a clinically significant improvement/deterioration in disease severity. Additionally, MCIDs provide a patient-centered approach to evaluating treatment efficacy, by considering whether patients experience a subjective improvement in their symptoms. Therefore, this literature review will examine the derivation and significance of MCIDs for various scoring systems in AIBDs.</p

Ophthalmologic examination characteristics.

<p>Ophthalmologic examination characteristics.</p

Representative clinical findings, SD-OCT and macular map from an ALS subject.

<p>OCT results were compared to the age-adjusted normative database by the integrated SD-OCT analysis software. Thin retinal areas are presented in a report format used in a typical clinic visit for ophthalmic examinations.</p

Bivariate fit for RNFL thickness and ALFRS-R progression rate.

<p>No significant correlation between mean RNFL thickness and ALSFRS-R progression rate was found. Again, data shown are from right eyes only, but the same result was obtained from left eyes.</p

Demographic characteristics of the study population.

<p>Demographic characteristics of the study population.</p

Differences in RNFL thickness between ALS subjects and normative database.

<p>Differences in RNFL thickness between ALS subjects and normative database.</p

Retinal thinning in amyotrophic lateral sclerosis patients without ophthalmic disease - Fig 6

<p><b>Bivariate fit for ALFRS-R score and intraocular pressure (A), and ALFRS-R score and visual acuity (B).</b> (A) No significant correlation between ALSFRS-R score and intraocular pressure (IOP) were found. (B) Similarly, there was no correlation between ALSFRS-R score and visual acuity (VA). Data shown are from right eyes only, but analyses with left eye data were comparable.</p

Mean and sectorial RNFL thickness comparison between ALS subjects and age-adjusted normal values.

<p>Total and six sector RNFL values were compared to the age-adjusted normal value utilized by the Spectralis SD-OCT system. The data presented here include mean ± standard error of the mean. Data for the right eye is indicated by OD and the left eye by OS. The right eye group showed significant thinning in total RNFL thickness, temporal sector RNFL thickness, and superonasal sector RNFL thickness. The left eye group had significant thinning in total RNFL thickness, temporal sector RNFL thickness, and superotemporal sector RNFL thickness.</p

Bivariate fit for RNFL thickness and ALFRS-R score.

<p>No significant correlation between mean RNFL thickness and ALSFRS-R score was found. Please note that most ALSFRS-R scores were relatively high, indicating mild ALS disease severity. Data shown are from right eyes only, but we obtained the same result from left eyes: there was no correlation observed between ALSFRS-R and RNFL thinning.</p