Multiple sclerosis

• In this situation, no routine laboratory test is recommended

Before treatment

• FBC with platelets
• AST
• ALT
• GGT
• TSHif neededRebif: thyroid tests recommended before treatment in all patients ^[6]; Betaferon and Plegridy: only if there is a history or sign of thyroid dysfunction ^[7,8].

At 1, 3 and 6 months, then periodically (at least twice a year)

• FBC with platelets
• AST
• ALT
• Urine protein:creatinine ratioif neededRegular monitoring of proteinuria and renal function (glomerulopathies and nephrotic syndrome described on interferon beta), especially in patients at renal risk ^[6,7,8,9].
• Serum creatinineif neededRegular monitoring of proteinuria and renal function (glomerulopathies and nephrotic syndrome described on interferon beta), especially in patients at renal risk ^[6,7,8,9].
• TSHif neededRebif: if the initial tests are abnormal, repeat them every 6 to 12 months; if they are normal, only if there are signs of thyroid dysfunction ^[6]. Betaferon, Plegridy: regular checks in patients with a thyroid history ^[7,8].

• No routine laboratory monitoring.
• Serum creatinine (known renal failure)if neededPatient with renal failure: renal function must be monitored during treatment ^[12].
• ASTif neededSevere, rare liver injuries have been described; regular clinical monitoring and immediate consultation if symptoms occur ^[12].
• ALTif neededSevere, rare liver injuries have been described; regular clinical monitoring and immediate consultation if symptoms occur ^[12].
• Bilirubinif neededSevere, rare liver injuries have been described; regular clinical monitoring and immediate consultation if symptoms occur ^[12].

Before treatment

• FBC with platelets
• ALT
• Serum β-hCG (woman of childbearing potential)if neededWoman of childbearing potential: pregnancy must be excluded before starting (contraindication, teratogenic) ^[14].
• IGRA (to look for latent tuberculosis before starting)if needednon-French guidelineThe US prescribing information asks for screening for latent tuberculosis before starting, as cases of tuberculosis were observed in the trials ^[15]. The European SmPC does not require it: it points out that this screening was not routine in the trials, that safety in latent infection is unknown and that a positive screen requires prior treatment ^[14]. In Germany, the KKNMS network requests it if a history is suspected or in case of increased individual risk ^[5].

Every 4 weeks for 6 months, then regularly

• ALT
• FBC (if signs of infection)if neededDuring treatment, the FBC is done according to clinical signs, for example an infection ^[14].

Before treatment

• FBC with lymphocytes
• Serum creatinine
• Urea
• Urine dipstick
• AST
• ALT
• Bilirubin

Every 3 months

• FBC with lymphocytes

At 3 and 6 months, then every 6 to 12 months

• Serum creatinine
• Urine dipstick
• Urea

Before treatment (results less than 6 months old)

• FBC with lymphocytes
• AST
• ALT
• Bilirubin
• Varicella serology (IgG)if neededNo confirmed history of chickenpox or complete vaccination: VZV serology, and vaccination before starting if it is negative ^[19,20].

Fingolimod: at 1, 3, 6, 9 and 12 months, then regularly

• AST
• ALT
• Bilirubin
• FBC with lymphocytes (at 3 months, then at least once a year)

Before treatment

• FBC with lymphocytes
• Anti-JC virus antibodies (JCV serology)

Within 3 months of starting

• ASTif neededThe European SmPC asks for liver function to be monitored “appropriately”, without setting a frequency, after serious liver disorders occurring at any time during treatment ^[21]. The German KKNMS network asks for baseline liver function tests and a mandatory measurement within 3 months, then advises a check every 3 months in the first half-year ^[5].
• ALTif neededThe European SmPC asks for liver function to be monitored “appropriately”, without setting a frequency, after serious liver disorders occurring at any time during treatment ^[21]. The German KKNMS network asks for baseline liver function tests and a mandatory measurement within 3 months, then advises a check every 3 months in the first half-year ^[5].
• GGTif neededThe European SmPC asks for liver function to be monitored “appropriately”, without setting a frequency, after serious liver disorders occurring at any time during treatment ^[21]. The German KKNMS network asks for baseline liver function tests and a mandatory measurement within 3 months, then advises a check every 3 months in the first half-year ^[5].

Every 6 months (if negative or low index)

• Anti-JC virus antibodies (JCV serology)

Before treatment

• Hepatitis B serology (HBsAg, anti-HBc, anti-HBs)
• FBC
• Serum immunoglobulins (IgG, IgA, IgM)
• ASTif neededThe European SmPC of Ocrevus asks for liver function tests before starting, then before the second infusion, following drug-induced liver injuries that are sometimes severe ^[24]. The US prescribing information for Ocrevus and Kesimpta requests them before starting ^[25,26]. The European SmPC of Kesimpta does not ask for them ^[27], and the German KKNMS network makes them mandatory for ocrelizumab, optional for ofatumumab ^[5].
• ALTif neededThe European SmPC of Ocrevus asks for liver function tests before starting, then before the second infusion, following drug-induced liver injuries that are sometimes severe ^[24]. The US prescribing information for Ocrevus and Kesimpta requests them before starting ^[25,26]. The European SmPC of Kesimpta does not ask for them ^[27], and the German KKNMS network makes them mandatory for ocrelizumab, optional for ofatumumab ^[5].
• Alkaline phosphataseif neededThe European SmPC of Ocrevus asks for liver function tests before starting, then before the second infusion, following drug-induced liver injuries that are sometimes severe ^[24]. The US prescribing information for Ocrevus and Kesimpta requests them before starting ^[25,26]. The European SmPC of Kesimpta does not ask for them ^[27], and the German KKNMS network makes them mandatory for ocrelizumab, optional for ofatumumab ^[5].
• Bilirubinif neededThe European SmPC of Ocrevus asks for liver function tests before starting, then before the second infusion, following drug-induced liver injuries that are sometimes severe ^[24]. The US prescribing information for Ocrevus and Kesimpta requests them before starting ^[25,26]. The European SmPC of Kesimpta does not ask for them ^[27], and the German KKNMS network makes them mandatory for ocrelizumab, optional for ofatumumab ^[5].

During treatment, according to clinical findings

• FBC (signs or symptoms of infection)if neededLate neutropenias, most often grade 1 or 2, have been reported at least 4 weeks after the last ocrelizumab infusion; the SmPC recommends measuring neutrophils in patients with signs or symptoms of infection ^[24].
• IgG (if severe or recurrent infections)if needednon-French guidelineThe US prescribing information for Ocrevus and Kesimpta has immunoglobulins monitored during treatment and after discontinuation until B-cell recovery, especially in case of infections ^[25,26]. The German KKNMS network measures IgG every 6 months ^[5]. The European SmPCs describe these falls without setting a monitoring frequency ^[24,27].

Before each year of treatment (years 1 and 2)

• FBC with lymphocytes
• HIV serology
• Hepatitis B serology
• Hepatitis C serology
• AST
• ALT
• Alkaline phosphatase
• Bilirubin
• IGRA (QuantiFERON)
• Serum β-hCG (woman of childbearing potential)if neededPregnancy must be excluded before each year of treatment ^[28].
• Varicella serology (IgG)if neededPatient never exposed to varicella-zoster virus: vaccinate in the absence of antibodies, 4 to 6 weeks before treatment ^[28].

2 and 6 months after the start of each year of treatment

• FBC with lymphocytes