Indications for: LEMTRADA
Relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease in adults who have had an inadequate response to ≥2 MS drugs.
Limitations of Use:
Not recommended for use in patients with clinically isolated syndrome.
The efficacy of Lemtrada was demonstrated in two studies (Study 1 and 2) that evaluated Lemtrada 12 mg in patients with relapsing-remitting multiple sclerosis (RRMS). Lemtrada was administered by intravenous infusion once daily over a 5-day course, followed one year later by intravenous infusion once daily over a 3-day course. Both studies included patients who had experienced at least 2 relapses during the 2 years prior to trial entry and at least 1 relapse during the year prior to trial entry. Neurological examinations were performed every 12 weeks and at the time of suspected relapse. Magnetic resonance imaging (MRI) evaluations were performed annually.
- Study 1 was a 2-year randomized, open-label, rater-blinded, active comparator (interferon beta1a 44 micrograms administered subcutaneously three times a week) controlled study in patients with RRMS.
- Patients entering Study 1 had Expanded Disability Status Scale (EDSS) scores of 5 or less and had to have experienced at least one relapse while on interferon beta or glatiramer acetate therapy.
- Patients were randomized to receive Lemtrada (n=426) or interferon beta-1a (n=202). The clinical outcome measures were the annualized relapse rate (ARR) over 2 years and the time to confirmed disability progression.
- Confirmed disability progression was defined as at least a 1 point increase above baseline EDSS (1.5 point increase for patients with baseline EDSS of 0) sustained for 6 months.
- The MRI outcome measure was the change in T2 lesion volume.
The annualized relapse rate was significantly lower in patients treated with Lemtrada than in patients who received interferon beta-1a. Time to onset of 6-month confirmed disability progression was significantly delayed with Lemtrada treatment compared to interferon beta1a. There was no significant difference between the treatment groups for the change in T2 lesion volume. The following results are for Lemtrada vs interferon beta-1a, respectively:
- ARR: 0.26 vs 0.52 (relative reduction, 49%; P <.0001)
- Proportion of patients with disability progression at year 2: 13% vs 21% (relative risk reduction, 42%; P =.0084)
- Percent of patients remaining relapse-free at year 2: 65% vs 47% (P <.0001)
- Percent change in T2 lesion volume from baseline: -1.3 vs -1.2 (P =.14)
- Study 2 was a 2-year randomized, open-label, rater-blinded, active comparator (interferon beta1a 44 micrograms administered subcutaneously three times a week) controlled study in patients with RRMS.
- Patients entering Study 2 had EDSS scores of 3 or less and no prior treatment for multiple sclerosis.
- Patients were randomized to receive Lemtrada (n=376) or interferon beta-1a (n=187).
- The clinical outcome measures were the annualized relapse rate (ARR) over 2 years and the time to confirmed disability progression, as defined in Study 1.
- The MRI outcome measure was the change in T2 lesion volume.
The annualized relapse rate was significantly lower in patients treated with Lemtrada than in patients who received interferon beta-1a. There was no significant difference between the treatment groups for the time to confirmed disability progression and for the primary MRI endpoint (change in T2 lesion volume). The following results are for Lemtrada vs interferon beta-1a, respectively:
- ARR: 0.18 vs 0.39 (relative reduction, 55%; P <.0001)
- Proportion of patients with disability progression at year 2: 8% vs 11% (relative risk reduction, 30%; P =.22)
- Percent of patients remaining relapse-free at year 2: 78% vs 59% (P <.0001)
- Percent change in T2 lesion volume from baseline: -9.3 vs -6.5 (P =.31)
Premedicate with high-dose corticosteroids (eg, methylprednisolone 1000mg or equivalent) immediately prior to infusion and for the first 3 days of each treatment course; may consider antihistamines and/or antipyretics. Administer antivirals for herpetic prophylaxis on 1st day of each treatment course and for ≥2 months following treatment or until CD4+ lymphocyte count ≥200cells/μL, whichever occurs later. Give by IV infusion over 4 hours. ≥17yrs: First course: 12mg daily for 5 consecutive days; Second course: 12mg daily for 3 consecutive days given 12 months after first course. May administer subsequent courses as needed (12mg daily for 3 consecutive days given ≥12 months after last dose of any prior courses).
<17yrs: not recommended.
Infection with HIV. Active infection.
Autoimmunity. Infusion reactions. Stroke. Malignancies.
Increased risk of serious autoimmune conditions (eg, immune thrombocytopenia, anti-glomerular basement membrane disease); treat promptly if occur. Obtain CBCs (w. differential), serum creatinine, urinalysis with urine cell counts prior to initiation and at monthly intervals, urine protein to creatinine ratio (at baseline), thyroid function tests (at baseline, every 3 months, then clinically indicated), and serum transaminases, total bilirubin (at baseline then periodically) until 48 months after last dose. Monitor for infusion reactions during and for ≥2 hours after each dose; discontinue immediately if severe reactions occur. Have equipment and personnel available to manage anaphylaxis. Stroke and cervicocephalic arterial dissection: monitor. Increased risk of malignancies (eg, thyroid cancer, melanoma, lymphoproliferative disorders); monitor. Perform baseline and yearly skin exams. Preexisting or ongoing malignancies; monitor. Cardiovascular or pulmonary function compromised: monitor more frequently. Glomerular nephropathies. Thyroid disorders. Other autoimmune cytopenias (eg, neutropenia, hemolytic anemia, pancytopenia). Autoimmune hepatitis. Hemophagocytic lymphohistiocytosis. Adult Onset Still's disease. Thrombotic thrombocytopenic purpura. Autoimmune encephalitis. Acquired hemophilia A. Perform annual HPV screening in female patients. Screen for TB and treat if positive prior to initiation. Avoid potential sources of Listeria monocytogenes (eg, deli or undercooked meat, soft cheeses, unpasteurized milk); monitor for symptoms. HBV/HCV carriers. Monitor for progressive multifocal leukoencephalopathy (PML); withhold and evaluate at the first sign suggestive of PML. Increased risk of acute acalculous cholecystitis; if suspected, evaluate and treat promptly. Monitor for other autoimmune cytopenias. Complete necessary immunizations ≥6 weeks prior to treatment initiation. Pregnancy. Advise females of reproductive potential to use effective contraception during and for 4 months after the last dose. Nursing mothers.
Monoclonal antibody, CD52 (recombinant, humanized).
Avoid live virus vaccines (after recent alemtuzumab therapy). Delay therapy for 6 weeks after varicella zoster vaccination. Increased risk of immunosuppression with concomitant antineoplastics or immunosuppressants. Additive effects following other previously received alemtuzumab-containing therapy (eg, Campath); caution.
Rash, headache, pyrexia, nasopharyngitis, nausea, UTI, fatigue, insomnia, URTI, 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, vomiting; autoimmune disorders, infusion reactions, stroke (may be serious), pneumonitis (monitor).
The elimination half-life was approximately 2 weeks and was comparable between courses. The serum concentrations were generally undetectable (<60 ng/mL) within approximately 30 days following each treatment course.
Generic Drug Availability:
Single-dose vial (1.2mL)—1