The role of real-world evidence in TRD/MDD decision making

INTRODUCTION

Esketamine nasal spray (NS) is approved by the European Medicines Agency, in combination with an SSRI or SNRI, for patients with treatment‑resistant depression (TRD).[1] After depressive symptoms improve, treatment is recommended for at least 6 months; however data on the durability of treatment effects and the risk of symptom recurrence or relapse following treatment cessation in real-world practice remain limited. This study presents the first structured real‑world post‑treatment follow‑up (PTFP) data on clinical outcomes after esketamine NS cessation.

AIMS

To evaluate the durability of the effectiveness of esketamine NS, in combination with antidepressants, after treatment cessation in adult patients with TRD, using real-world data from the Esketamine CoHOrt (ECHO) study.

METHODS

ECHO was a prospective, non-interventional, open-label study in Belgium, Germany, Israel, Italy, Netherlands, Spain and Sweden. Esketamine NS was prescribed per local clinical practice, independent of study participation. The study included a variable-length treatment period (TP) and a 6-month PTFP after esketamine NS cessation. Clinical outcomes in the PTFP included Montgomery-Åsberg Depression Rating Scale (MADRS) total score, relapse rate (for patients who achieved remission/response during the TP/PTFP) and the reason for and time to first relapse. Outcomes are reported for all patients and stratified by TP remission (MADRS ≤10) and response (≥50% improvement in MADRS from treatment initiation) subgroups, using the full analysis set to 6 months after esketamine NS treatment cessation.

RESULTS

Overall, 301/570 patients enrolled in the TP continued to the PTFP. Mean MADRS total score in the PTFP are reported in the Table. At any point during the TP, 166/301 patients achieved remission or response; 81.3% (135/166) of these patients remained relapse-free during the PTFP. Of the 31 patients who relapsed, mean (SD) time to first relapse in the PTFP was 52.4 (47.9) days. First relapses in the PTFP were defined according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria (58.1% [18/31]), and by a confirmed MADRS total score of ≥22 (41.9% [13/31]).[2]

For patients who achieved remission or response at the TP endpoint (following 48 weeks of esketamine NS treatment), 93.2% (69/74) and 85.4% (105/123) remained relapse-free during the PTFP.

CONCLUSION

In this real-world cohort, most patients who achieved remission or response with esketamine NS remained relapse-free during the 6 months after treatment cessation. Achieving remission with esketamine NS reduced relapse risk compared with response alone, supporting the clinical relevance of achieving and consolidating stable remission before treatment cessation. These ECHO data thus provide important clinical guidance into TRD treatment trajectories.

TABLE

	MADRS total score in PTFP, mean (standard deviation) N
	Patient status at end of TP
PTFP visit	All patients in PTFP	Achieved remission	Achieved response	Did not achieve remission or response
Baseline	19.6 (11.7) 296	5.2 (3.7) 74	9.0 (5.7) 123	27.4 (8.4) 171
Week 4	18.7 (12.1) 222	5.7 (4.9) 59	10.3 (8.7) 95	25.0 (10.0) 122
Week 24	18.7 (11.4) 208	9.8 (8.8) 49	13.1 (9.6) 83	22.3 (10.6) 122

MADRS: Montgomery-Åsberg Depression Rating Scale; PTFP: post-treatment follow-up period; TP: treatment period.

References

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