Introduction:Results from the open-label extension of the phase 3b CONQUER trial are presented to evaluate the effectiveness and safety of galcanezumab, a monoclonal antibody targeting calcitonin gene-related peptide, for up to 6 months in patients with multiple prior migraine preventive treatment failures. Methods: Patients were 18-75 years old with episodic or chronic migraine and 2-4 standardof-care migraine preventive medication category failures. After 3 months of randomized treatment with galcanezumab (120 mg/month with 240 mg loading dose; n = 232) or placebo (n = 230), patients entered a 3-month open-label extension (120 mg/month galcanezumab with a blinded 240 mg loading dose for previous-placebo patients). Primary efficacy measure was mean change from double-blind baseline in monthly migraine headache days. Results: A total of 432/449 patients (96%) who entered open-label treatment completed the study. Mean change in monthly migraine headache days in the total population, which was -1.3 for placebo and -4.4 for galcanezumab patients at the end of double-blind treatment (p \ 0.001), was -5.2 and -5.6, respectively, at the end of open-label treatment with galcanezumab. Among patients with episodic migraine, mean change in monthly migraine headache days had been -0.6 for placebo and -2.8 for galcanezumab after double-blind treatment (p \ 0.001) and was -4.5 and -3.8, respectively, after open-label treatment. Among patients with chronic migraine, mean change in monthly migraine headache days had been -2.5 for placebo and -6.6 for galcanezumab after double-blind treatment (p \ 0.001) and was -6.5 and -8.2, respectively, after open-label treatment. Adverse events were similar to those observed during double-blind placebo treatment. Review of data in elderly patients (65-75 years of age) indicated that galcanezumab was well tolerated in this age group, with no safety issues identified.
The study evaluated whether the renal function decline rate per year with age in adults varies based on two primary statistical analyses: cross-section (CS), using one observation per subject, and longitudinal (LT), using multiple observations per subject over time. A total of 16628 records (3946 subjects; age range 30-92 years) of creatinine clearance and relevant demographic data were used. On average, four samples per subject were collected for up to 2364 days (mean: 793 days). A simple linear regression and random coefficient models were selected for CS and LT analyses, respectively. The renal function decline rates per year were 1.33 and 0.95 ml/min/year for CS and LT analyses, respectively, and were slower when the repeated individual measurements were considered. The study confirms that rates are different based on statistical analyses, and that a statistically robust longitudinal model with a proper sampling design provides reliable individual as well as population estimates of the renal function decline rates per year with age in adults. In conclusion, our findings indicated that one should be cautious in interpreting the renal function decline rate with aging information because its estimation was highly dependent on the statistical analyses. From our analyses, a population longitudinal analysis (e.g. random coefficient model) is recommended if individualization is critical, such as a dose adjustment based on renal function during a chronic therapy.
Objective
To evaluate changes in interictal burden with galcanezumab versus placebo in patients with episodic (EM) or chronic migraine (CM).
Background
The disruptive effects of migraine occur both during attacks (ictal period) and between attacks (interictal period), affecting work, school, family, and social life. Migraine clinical trials typically assess ictal burden endpoints, neglecting interictal burden.
Methods
CONQUER was a 3‐month, double‐blind study that randomized adult patients with EM or CM who had experienced failure of two to four standard‐of‐care migraine preventive medication categories to receive monthly galcanezumab (n = 232) or placebo (n = 230), followed by 3 months of open‐label galcanezumab. The mean change in interictal burden, a secondary objective, was measured using the four‐item Migraine Interictal Burden Scale (MIBS‐4). The total score for MIBS‐4 can range from zero to 12, with scores ≥5 indicating severe interictal burden. Post hoc analyses evaluated shifts in MIBS‐4 severity categories and item‐level improvement.
Results
The MIBS‐4 total score indicated severe interictal burden at baseline (mean [SD]: all patients, 5.5 [3.5]; EM, 5.0 [3.4]; CM, 6.2 [3.5]). Reductions in the MIBS‐4 score were significantly greater with galcanezumab versus placebo at Month 3 (mean [SE]: all patients −1.9 [0.2] vs. −0.8 [0.2], p < 0.0001; EM, −1.8 [0.3] vs. −1.1 [0.3], p = 0.033; CM, −1.8 [0.4] vs. −0.3 [0.4], p < 0.001), with further improvement at Month 6 after all patients had received galcanezumab (mean [SE]: all patients, −2.4 [0.2] vs. −2.0 [0.2]; EM, −2.3 [0.3] vs. −2.2 [0.3]; CM, −2.1 [0.4] vs. −1.5 [0.4]). The percentage of patients with severe interictal burden decreased substantially for the galcanezumab‐treated patients, from 59% (137/232) at baseline to 27% (58/217) at Month 6 (EM from 51% [70/137] to 23% [30/131]; CM from 71% [67/95] to 33% [28/86]).
Conclusion
In addition to the known efficacy of galcanezumab in the ictal period, these findings suggest treatment with galcanezumab results in a significant reduction in interictal burden.
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