IMPROVEMENT OF PREDOMINANT NEGATIVE SYMPTOMS IN PATIENTS WITH SCHIZOPHRENIA ON PALIPERIDONE PALMITATE 6-MONTH LONG-ACTING INJECTABLE: POST-HOC ANALYSIS OVER 3 YEARS

Background

Schizophrenia is an often debilitating disorder with persistent negative symptoms, cognitive impairments and functional deficits, which are key contributors to long-term disability. Negative symptoms often persist long-term, and their remission is critical for functional recovery. Paliperidone palmitate 6-month formulation (PP6M) has demonstrated efficacy in preventing relapse in patients with schizophrenia. This post-hoc analysis of phase 3 studies assessed the effect of PP6M over 1–3 years in patients with predominant negative symptoms (PNS).

Methods

Adults previously stabilized on PP1M or PP3M in a 12-month (M) phase 3 noninferiority double-blind (DB) study (NCT03345342), who completed the DB phase without relapse, and continued on PP6M in a 24M single-arm, open-label extension (OLE; NCT04072575) study, were analyzed. Improvements in the Positive and Negative Syndrome Scale for Negative Subscale Score (PANSS-NSS) and Negative Symptoms Factor Score (PANSS-NSFS), secondary negative symptoms (SNS; Disorganized Thoughts, Uncontrolled Hostility-Excitement, and Anxiety-Depression), Personal and Social Performance (PSP), and PANSS total score over 36M were assessed in a subset of pts with PNS from DB and OLE phases. PNS was defined as a clinically meaningful elevation of negative-symptom severity (≥2 items in the moderate or greater range [≥4]) and a global negative symptom burden exceeding a predefined threshold (sum score > 20), while positive and depressive symptoms remained low/< moderate [ < 4].

Results

Of 701 patients from the DB phase, 87 had PNS (mean[SD] age: 41.6 (11.93) years; 71.3% male) of which 80 completed the DB phase; 31 patients continued PP6M in the OLE. At baseline (BL), the mean (SE) PANSS NSS was 20.8 (0.26; n=86). Scores improved to 18.4 (0.43; n=80) at 12M, a mean (SE) change from baseline (CFB) was −2.3 (0.36; 95% CI: −3.03, −1.60; p < 0.001), and further improved to 16.3 (0.84; n=23) at 36M (mean [SE] CFB: −3.9 [0.91; 95% CI: −5.75 −1.98]; p < 0.001). Median (range) CFB in PANSS NSS were −2.0 (−10, 6) at 12M and –5.0 (–11, 7) at 36M. At BL, the mean (SE) PANSS NSFS was 19.7 (0.25; n=86). Scores improved to 16.7 (0.40; n=80) at 12M, with a mean (SE) CFB of −3.0 (0.37; 95% CI: −3.70, −2.23; p < 0.001) and were maintained through 36M at 15.1 (0.83; n=23). Median (range) CFB in PANSS NSFS were −2.0 (−11, 6) at 12M and −5.0 (−12, 7) at 36M. Mean (SE) CFB to 36M (n=22) in SNS were minimal for Disorganized Thoughts (−2.9 [0.56; 95% CI: −4.08, −1.74; p < 0.001], from BL of 15.2 [0.34]); for Uncontrolled Hostility-Excitement (0.0 [0.34; 95% CI: −0.66, 0.75; p=0.894], from BL of 4.7 [0.10]); and for Anxiety-Depression (−0.9 [0.50; 95% CI: −1.96, 0.14; p=0.086], from BL of 5.4 [0.19]). The mean (SE) BL PANSS total score was 58.5 (0.68). Mean (SE) CFB at 12M: −5.0 (0.76), 95% CI (−6.54, −3.51) p < 0.001, improved to −9.5 (1.76), 95% CI (−13.21, −5.88), p < 0.001at 36M; median (range) CFB 12M: −4.0 (−22, 13), 36M: −12.5 (−21, 6). The mean (SE) BL PSP total score was 59.0 (1.18). Mean (SE) CFB to 12M was 4.9 (0.84; 95% CI: 3.18, 6.52; p < 0.001), increasing to 10.5 (2.09; 95% CI: 6.21, 14.87; p < 0.001) at 36M. Median (range) CFB in PSP were 4.0 (−9, 27) at 12M and 10.5 (−5, 33) at 36M.

Conclusion

In patients with PNS, significant reductions were observed in PANSS NSS and PANSS NSFS, with improvements maintained through long term follow up of 1–3 years. Corresponding significant improvements in PSP scores demonstrated meaningful enhancement in personal and social functioning. Together, these findings support that the PP6M treatment was associated with consistent and clinically meaningful improvements in negative symptoms and functioning over 3 years in patients with schizophrenia displaying PNS.