Novel and Emerging Treatments in Relapsing-Remitting MS
Novel and Emerging Treatments in Relapsing-Remitting MS
In CHOICE, daclizumab was generally well tolerated, and the incidence of common adverse events was similar across treatment groups. However, serious adverse events (SAEs) were seen more commonly in the daclizumab and IFNβ treatment arms (13% SAEs) in comparison to the IFNβ and placebo arm (5% SAEs). The most commonly observed SAEs were infections, which resolved with standard therapies. Cutaneous events were also seen more commonly with daclizumab versus placebo (24 vs. 6%). Two malignancies were observed, both in patients on daclizumab: one case of breast ductal carcinoma in-situ in a patient with a positive family history of breast cancer, and one case of pseudomyxoma peritonei, which was a recurrence of a pre-existing condition. There were no observed opportunistic infections or deaths.
In SELECT, the incidence of SAEs was relatively similar across treatment arms (5, 6, and 8% in placebo, low-dose daclizumab, high-dose daclizumab, respectively). SAEs that occurred more frequently in the daclizumab treatment arms included serious infections (2%), serious cutaneous events (1%), and elevations in liver function tests (4%). There was a single death in SELECT because of a psoas muscle abscess complication in a patient recovering from a serious skin adverse event; and a contributory role of daclizumab could not be excluded.
In SELECTION, the incidence of serious infections (2%) and serious cutaneous events (1%) was identical to SELECT, whereas AST/ALT elevations more than five times the upper limit of normal were less common (1.5 vs. 4% in SELECTION vs. SELECT). In patients who were on continuous low-dose daclizumab treatment throughout the study period, there were no AST/ALT elevations more than five times the upper limit of normal, or serious cutaneous events during the second year of treatment. Importantly, there was one reported death in SELECTION because of autoimmune hepatitis in the 300 mg daclizumab treatment arm and the contributory role of daclizumab could not be excluded in this case.
The safety profile of daclizumab in DECIDE was consistent with previous phase II studies. The incidence of adverse events was similar in both treatment arms (91% in both arms), and the majority were mild-to-moderate in severity. Serious adverse events excluding MS relapse were seen more frequently in the daclizumab group (15% in daclizumab arm vs. 10% in IFNβ-1a arm), as were treatment discontinuations because of adverse events (14% in daclizumab arm vs. 9% in IFNβ-1a arm). Adverse events of special interest occurring more frequently in the daclizumab treatment group in comparison to IFNβ-1a included serious infections (4 vs. 2%), cutaneous events (any cutaneous event: 37 vs. 19%; serious cutaneous event: 2 vs. <1%), and liver enzyme abnormalities (6 vs. 3%). There was a single death in the daclizumab arm after the patient withdrew from the study because of aspiration pneumonia following a severe MS relapse involving the brainstem. There were three reported deaths in the IFNβ-1a arm because of one case each of suicide, myocardial infarction, and metastatic pancreatic cancer. Additional safety results from DECIDE are expected in the near future.
Daclizumab: Safety
In CHOICE, daclizumab was generally well tolerated, and the incidence of common adverse events was similar across treatment groups. However, serious adverse events (SAEs) were seen more commonly in the daclizumab and IFNβ treatment arms (13% SAEs) in comparison to the IFNβ and placebo arm (5% SAEs). The most commonly observed SAEs were infections, which resolved with standard therapies. Cutaneous events were also seen more commonly with daclizumab versus placebo (24 vs. 6%). Two malignancies were observed, both in patients on daclizumab: one case of breast ductal carcinoma in-situ in a patient with a positive family history of breast cancer, and one case of pseudomyxoma peritonei, which was a recurrence of a pre-existing condition. There were no observed opportunistic infections or deaths.
In SELECT, the incidence of SAEs was relatively similar across treatment arms (5, 6, and 8% in placebo, low-dose daclizumab, high-dose daclizumab, respectively). SAEs that occurred more frequently in the daclizumab treatment arms included serious infections (2%), serious cutaneous events (1%), and elevations in liver function tests (4%). There was a single death in SELECT because of a psoas muscle abscess complication in a patient recovering from a serious skin adverse event; and a contributory role of daclizumab could not be excluded.
In SELECTION, the incidence of serious infections (2%) and serious cutaneous events (1%) was identical to SELECT, whereas AST/ALT elevations more than five times the upper limit of normal were less common (1.5 vs. 4% in SELECTION vs. SELECT). In patients who were on continuous low-dose daclizumab treatment throughout the study period, there were no AST/ALT elevations more than five times the upper limit of normal, or serious cutaneous events during the second year of treatment. Importantly, there was one reported death in SELECTION because of autoimmune hepatitis in the 300 mg daclizumab treatment arm and the contributory role of daclizumab could not be excluded in this case.
The safety profile of daclizumab in DECIDE was consistent with previous phase II studies. The incidence of adverse events was similar in both treatment arms (91% in both arms), and the majority were mild-to-moderate in severity. Serious adverse events excluding MS relapse were seen more frequently in the daclizumab group (15% in daclizumab arm vs. 10% in IFNβ-1a arm), as were treatment discontinuations because of adverse events (14% in daclizumab arm vs. 9% in IFNβ-1a arm). Adverse events of special interest occurring more frequently in the daclizumab treatment group in comparison to IFNβ-1a included serious infections (4 vs. 2%), cutaneous events (any cutaneous event: 37 vs. 19%; serious cutaneous event: 2 vs. <1%), and liver enzyme abnormalities (6 vs. 3%). There was a single death in the daclizumab arm after the patient withdrew from the study because of aspiration pneumonia following a severe MS relapse involving the brainstem. There were three reported deaths in the IFNβ-1a arm because of one case each of suicide, myocardial infarction, and metastatic pancreatic cancer. Additional safety results from DECIDE are expected in the near future.
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