Meaningful Within-Patient Change Threshold Range for the FACIT-Fatigue in Paroxysmal Nocturnal Hemoglobinuria (PNH)

OBJECTIVES: Derivation of patient-centered, evidence based meaningful within-patient change thresholds (MWPC) for the FACIT-Fatigue in PNH reflecting patient experience using anchor-based methods. PNH is a rare disease lacking rigorously determined MWPC for the FACIT-Fatigue.

METHODS: The analysis used data from the APPLY-PNH study with a PNH patient population with residual anemia despite use of C5 inhibitor treatment where FACIT-Fatigue changes from baseline to Days 126, 140, 154 and 168 during the 24 week-active-controlled treatment period were a secondary endpoint. A patient global impression of fatigue (PGIS) was included to determine the anchor-based MWPC from baseline in FACIT-Fatigue scores, regardless of patient treatment assignment. Data from patient interviews conducted at the end of the treatment period supported MWPC determination.

RESULTS: Using a one level change in severity category of PGIS as indicated by patient interviews as meaningful change, the MWPC for the FACIT-Fatigue change at Days 126, 140, 154, and 168 was 7.5-9.5 points. Results from patient interviews were described individually and collapsed into a group of patients who said that they had experienced meaningful improvement in 50% or more of these individual perceptions of fatigue. The median of change in the FACIT-Fatigue scores was 13.2 and was weighted by transporting the scores to the overall study population (median, 5.8). These values enclosed the range and were therefore considered as supportive of the MWPC derived from the PGIS.

CONCLUSIONS: A change in the range of 7.5-9.5 points on the FACIT-Fatigue would be a useful starting point for classifying individuals as meaningfully changed, thereby identifying a MWPC for the FACIT-Fatigue in patients with PNH with anemia.