The following serious adverse reactions are described below and elsewhere in the labeling:
- Autoimmunity [see BOXED WARNINGand WARNINGS AND PRECAUTIONS]
- Infusion reactions [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
- Malignancies [see WARNINGS AND PRECAUTIONS]
- Immune Thrombocytopenia [see WARNINGS AND PRECAUTIONS]
- Glomerular Nephropathies [see WARNINGS AND PRECAUTIONS]
- Thyroid Disorder [see WARNINGS AND PRECAUTIONS]
- Other Autoimmune Cytopenias [see WARNINGS AND PRECAUTIONS]
- Infections [see WARNINGS AND PRECAUTIONS]
- Pneumonitis [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In controlled clinical trials (Study 1 and Study 2), a total of 811 patients with relapsing forms of MS received LEMTRADA. A total of 811 patients received 1 course of therapy, and 789 patients received a second course of therapy at 12 months. The overall follow-up in the controlled trials was equivalent to 1622 patient years, with an additional 3411 person-years of follow-up in an open label extension study. The population was 1855 years of age, 65% were female, and 92% were Caucasian.
Most Common Adverse Reactions
In clinical trials, the most common adverse reactions with LEMTRADA (in at least 10% of patients and more frequently than in interferon beta-1a) were rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infection, urticaria, pruritus, thyroid gland disorders, fungal infection, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting.
Table 1 lists adverse reactions occurring in ≥ 5% of LEMTRADA-treated patients in Study 1 and 2 and at the same or at a higher rate than interferon beta-1a.
Table 1: Adverse Reactions in the Pooled 2-Year Active-Controlled Studies in Patients with Relapsing-Remitting Multiple Sclerosis
|Urinary tract infection||19||8|
|Upper respiratory tract infection||16||13|
|Herpes viral infection||16||3|
|Thyroid gland disorders||13||3|
|Pain in extremity||12||9|
|Blood in urine||8||3|
|Decrease in CD4 lymphocytes||6||2|
|Decrease in CD8 lymphocytes||6||2|
|Decrease in T-lymphocyte count||5||3|
|Abnormal uterine bleeding||5||1|
Nearly all (99.9%) patients treated with LEMTRADA in MS clinical trials experienced lymphopenia. The lowest lymphocyte counts occurred approximately by 1 month after each course of treatment. The mean lymphocyte count at 1 month after LEMTRADA treatment was 0.25 x 109L (range 0.02-2.30 x 109L) and 0.32 (0.02-1.81 x 109L) for treatment courses 1 and 2, respectively. Total lymphocyte counts increased to reach the lower limit of normal in approximately 40% of patients by 6 months after each LEMTRADA treatment course and approximately 80% of patients by 12 months after each course [see CLINICAL PHARMACOLOGY].
Suicidal Behavior Or Ideation
In clinical studies, 0.6% of patients in both the LEMTRADA and interferon beta-1a groups had events of attempted suicide or suicidal ideation. There were no completed suicides in either clinical study treatment group. Suicidal behavior or ideation occurred in patients with or without a history of a psychiatric or thyroid disorder. Advise patients to report immediately any symptoms of depression or suicidal ideation to the prescribing physician.
As with all therapeutic proteins, there is potential for immunogenicity. Using an enzymelinked immunosorbent assay (ELISA) and a competitive binding assay, anti-alemtuzumab binding antibodies were detected in 62%, 67%, and 29% of LEMTRADA-treated patients, at months 1, 3, 12 (Course 1) as well as 83%, 83%, and 75% of LEMTRADAtreated patients at months 13, 15, and 24 (Course 2). Samples that tested positive for binding antibodies were further evaluated for evidence of in vitro inhibition using a flow cytometry assay. Neutralizing antibodies were detected in 87%, 46%, and 5% of positive binding antibody patients at months 1, 3, 12 (Course 1) as well as 94%, 88%, and 42% of positive binding antibody patients at months 13, 15, and 24 (Course 2). Antialemtuzumab antibodies were associated with decreased alemtuzumab concentration during Course 2 but not Course 1. There was no evidence from clinical trials that the presence of binding or inhibitory anti-alemtuzumab antibodies had a significant effect on clinical outcomes, total lymphocyte count, or adverse events.
The incidence of antibodies is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including inhibitory antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to LEMTRADA with the incidence of antibodies to other products may be misleading.
The following adverse reactions, not described elsewhere, were identified during postapproval use of alemtuzumab (CAMPATH) for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), as well as for the treatment of other disorders, generally at higher and more frequent doses (e.g., 30 mg) than that recommended in the treatment of MS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Congestive heart failure, cardiomyopathy, and decreased ejection fraction in non-MS patients previously treated with potentially cardiotoxic agents.