Table 2.

FDA Recommended Pre-Treatment Screening and Monitoring during Treatment with Newer Disease Modifying Therapies.

Disease Modifying Therapy	Routine Screening Prior to Initiation	Routine Monitoring while on Treatment
Oral therapies
Teriflunomide (AUBAGIO®, Sanofi Genzyme, Massachusetts, United States) [22,144,196]	Baseline CBC and LFTs (within 6 months before starting therapy) Latent tuberculosis screening with a tuberculin skin test. Baseline blood pressure Pregnancy test, counseling on use of effective contraception in males and females of reproductive potential	CBC if signs/symptoms of hematologic toxicity, LFTs monthly for 6 months, then every 6 months thereafter Periodic blood pressure monitoring Confirm use of effective contraception at each encounter for both male and female patients during therapy
Dimethyl fumarate (TECFIDERA®, Biogen Idec, Massachusetts, United States) [144,197,198]	Baseline CBC with absolute lymphocyte count Baseline LFTs and renal function tests Pregnancy test, counseling on use of effective contraception in females of reproductive potential	CBC with lymphocyte count after 6 months, every 6 to 12 months thereafter or as clinically indicated LFTs and renal function tests after 3 and 6 months, every 6 to 12 months thereafter and as clinically indicated Confirm use of effective contraception at each encounter for female patients during therapy
Fingolimod (GILENYA®, Novartis, Basel, Switzerland) [37,42,199,200,201,202]	Baseline CBC and LFTs (within 6 months before starting therapy) Baseline ECG, review of medications (concomitant use of medications causing bradycardia or conduction abnormalities) Baseline ophthalmologic examination (or optical coherence tomography) Baseline skin examination (in most centers) Pregnancy test, counseling on use of effective contraception in females of reproductive potential VZV serology or confirmation of prior exposure. VZV vaccine in non-immunized patients prior to treatment start. Baseline clinical evaluation of respiratory function	CBC after 1, 3 and 6 months and periodically thereafter. LFTs after 1 month then every 3 months for the first year, then periodically thereafter First-dose cardiac monitoring Periodic blood pressure monitoring Ophthalmologic examination (or optical coherence tomography) 3–4 months after initiation, and at any time if patient reports visual disturbances. Regular ophthalmologic follow-up in patients with diabetes mellitus or a history of uveitis Self-check or dermatologist examination annually (in many centers) Confirm use of effective contraception at each encounter for female patients during therapy
Siponimod (MAYZENT®, Novartis, Basel, Switzerland) [203]	CYP2C9 genetic testing Baseline ECG. Baseline blood pressure Baseline ophthalmologic examination Baseline CBC and LFTs (within 6 months before starting therapy) Pregnancy test, counseling on use of effective contraception in females of reproductive potential VZV serology or confirmation of prior exposure. VZV vaccine in non-immunized patients prior to treatment start Baseline evaluation of respiratory function	First-dose observation in high-risk patients only. Periodic blood pressure monitoring Ophthalmologic examination if clinically indicated CBC and LFT 3–6 months after starting treatment, then every 6–12 months Confirm use of effective contraception at each encounter for female patients during therapy
Ozanimod (ZEPOSIA®, Celgene Corporation, New Jersey, United States) [46,204,205]	Obtain CBC and LFTs (within 6 months before starting therapy) Baseline ECG and baseline blood pressure Baseline ophthalmologic examination Pregnancy test, counseling on use of effective contraception in females of reproductive potential VZV serology or confirmation of prior exposure. VZV vaccine in non-immunized patients prior to treatment start. Baseline evaluation of respiratory function	CBC and LFT 3–6 months after starting treatment, then every 6–12 months Periodic blood pressure monitoring Ophthalmologic examination id clinically indicated onfirm use of effective contraception at each encounter for female patients during therapy
Cladribine (MAVENCLAD®, Merck group, Darmstadt, Germany) [206]	CBC including absolute lymphocyte count and LFTs before each dose Pregnancy test, counseling on use of effective contraception in females and males of reproductive potential for at least 6 months after each dose Baseline Antibodies to VZV; VZV vaccination in antibody-negative patients 1 month prior to treatment initiation Tuberculosis screening, Hepatitis B and C panels, and HIV serology Standard age-appropriate cancer screening recommendations	CBC at 2 and 6 months after each dose Confirm use of effective contraception at each encounter for female patients during therapy Anti-herpes prophylaxis with acyclovir in patients with ALC less than 200 cells per microliter, and close monitoring for infections if ALC is below 500 cells per microliter
Infusion therapies
Natalizumab (TYSABRI®, Biogen Idec, Massachusetts, United States) [84,126,128,207,208,209,210]	Anti-JCV antibody serostatus and index Baseline CBC and LFTs Obtain a recent brain MRI (usually within 3 months)	Anti-JCV antibody testing every 6 to 12 months in seronegative patients for the first 2 years, and every 3–6 months thereafter CBC and LFT after 1, 3 and 6 months and every 6 months thereafter. Brain MRI yearly in JCV seronegative patients for the first 2 years, and every 3–6 months thereafter depending on JCV serostatus and risk of PML Neutralizing antibodies to natalizumab 6 months after initiation or at any time in patients with hypersensitivity reactions or disease exacerbations while on therapy.
Alemtuzumab (LEMTRADA®, Sanofi, Genzyme, Massachusetts, United States) [116,211]	CBC, TSH, LFTs, creatinine, urine analysis with cell counts and urine protein to creatinine ratio Baseline skin (melanoma screening) and gynecologic (HPV/cervical dysplasia screening) exam Pregnancy test, counseling on use of effective contraception in females of reproductive potential for at least 4 months after each cycle Tuberculosis screening, Hepatitis B and C panels, and HIV serology VZV serology or confirmation of prior exposure. VZV vaccine in non-immunized patients prior to treatment start. Counselling on Listeria monocytogenes infection risk 2 weeks prior treatment initiation and while on treatment (avoidance of undercooked deli meat, seafood, or poultry, dairy products made with unpasteurized milk, and soft cheeses)	TSH every 3 months for 48 months following last course (second or subsequent course) CBC, creatinine and urine analysis with cell counts monthly for 48 months following last course (second or subsequent course). LFTs periodically until 48 months after the last dose Anti-viral prophylaxis with acyclovir 200 mg p.o twice daily for 24 months starting day 1 of first cycle, or for continue for a minimum of two months following treatment or until the CD4+ lymphocyte count is at least 200 cells per microliter, whichever occurs later Perform yearly skin and gynecologic exam Confirm use of effective contraception at each encounter for female patients during therapy
Ocrelizumab (OCREVUS®, Genentech, California, United States) [212]	Baseline CBC and LFTs Hepatitis B and C and Tuberculosis screening. Pregnancy test, counseling on use of effective contraception in females of reproductive potential for at least 2 months after each cycle Vaccines according to age-appropriate immunization guidelines at least 6 weeks prior to treatment start Age-appropriate breast cancer screening	CBC and LFTs every 6 months Immunoglobulin levels in patients with severe or recurrent infections Confirm use of effective contraception at each encounter for female patients during therapy

Abbreviations: ALT: alanine aminotransferase; AST: aspartate aminotransferase; CBC: complete blood count; ECG: electrocardiogram; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human Immunodeficiency Virus; LFT: liver function test; TSH: Thyroid-stimulating hormone. CBC and LFT dosage with oral medications are checked every 3–6 months depending on practice and patient profile.