2. Challenges in assessment of therapeutic efficacy
Management algorithm proposed by Jodele et al (24) stratifies high risk TA-TMA patients as indication for eculizumab use with therapeutic drug level monitoring. Clinical utility of this guideline is limited in local setting as measurement of both soluble terminal complement complex (sC5b-9) and eculizumab drug level are not readily available in local laboratories. Long turnaround time due to transportation to overseas accredited laboratories limits its use in facilitating timely clinical decision making and management. Besides, eculizumab is currently licensed only for treating atypical hemolytic-uremic syndrome (HUS) and paroxysmal nocturnal hemoglobinuria. Off-label use of eculizumab for TA-TMA costs USD$6,700 per 300mg vial, which has great financial implication on public healthcare system. Moreover, although decline in glomerular filtration rate (GFR) and thus degree of kidney injury is better evaluated by cystatin C (by Larsson formula) instead of serum creatinine (by Schwartz formula) which is a late and insensitive parameter particularly in young patients with low muscle mass and low creatinine generation rates, cystatin C test is also not available in local setting.