Biologicals

Mechanism of action

Dosage regimen

Onset of action

The main adverse effects

Controls and its frequency

Pregnancy

References

TNF-alpha-blocking agents

1.

Etanercept

Blocking of TNF receptors

25 mg twice weekly; subcutaneously

Between 2 and 12 weeks

Infection, skin disorders (pruritus, herpes simplex, local skin reactions at the injection site), the risk of malignancy is unclear

Before therapy:

CBC with renal and liver functional test, chest X-ray, TST (tuberculin skin test) and/or interferon gamma assays for ruling out of TB, infection and heart failure with NYHA class III–IV

During therapy:

CBC, renal and liver functional test, CRP, ESR every 14 days for the first 2 months, then each month for the next 2 months and thereafter each month

Pregnancy category B: discontinue at least 3 weeks prior to conception

[8, 30, 35, 45, 46, 62, 69, 70, 77, 81]

2.

Infliximab

Blocking of the soluble and transmembrane forms of TNF-α

3–5 mg/kg intravenous infusion at weeks 0, 2, 6, and every 8 weeks thereafter

Between 2 and 3 weeks, if there is no onset of effect after 8–12 weeks, the dosage can be increased up to 7.5 mg/kg

Gastrointestinal, central nervous disorders (headache, vertigo), infection, skin disorders (pruritus, urticaria), infusion reaction, the risk of malignancy is unclear

Before therapy:

CBC with renal and liver functional test, chest X-ray, TST (tuberculin skin test) and/or interferon gamma assays for ruling out TB, ruling out of infection and heart failure with NYHA class III–IV

During therapy:

CBC, renal and liver functional test, CRP, ESR every 14 days for the first 2 months, then each month for the next 2 months and thereafter each month

Pregnancy category B: discontinue at least 6 months prior to conception

[1, 3, 5–7, 12, 16, 17, 25, 26, 29, 50, 51, 56, 57, 66, 68, 69, 77, 79, 80, 83]

3.

Adalimumab

Blocking of TNF-α receptors

40 mg biweekly;

subcutaneously

Between 2 and 3 weeks, if there is no onset of effect after 8–12 weeks, the dosage can be increased up to 40 mg weekly

Gastrointestinal, central nervous disorders (headache, vertigo), infection, skin disorders (pruritus, urticaria, herpes simplex), local skin reactions at the injection site, hypertension, flu-like symptoms, decreased hemoglobin, weight loss, the risk of malignancy is unclear

Before therapy:

CBC with renal and liver functional test, chest X-ray, TST (tuberculin skin test) and/or interferon gamma assays for ruling out TB, ruling out of infection and heart failure with NYHA class III–IV

During therapy:

CBC with differential blood count, liver functional test and urinalysis: every 7–14 days for the first 2 months and every 4 weeks thereafter

Pregnancy category B: discontinue at least 5 months prior to conception

[9, 16, 17, 22, 24, 25, 28, 31, 38, 39, 41, 45, 48, 49, 59, 64, 67, 69, 75, 77, 85]

4.

Golimumab

Blocking of TNF-α receptors

50 mg once monthly

Between 2 and 3 weeks, if there is no onset of effect after 8–12 weeks, the agent should be discontinued

Gastrointestinal, central nervous disorders (headache, vertigo, paraesthesia), infection, skin disorders (pruritus, urticaria, herpes simplex), local skin reactions at the injection site, hypertension, flu-like symptoms, decreased hemoglobin, weight loss, the risk of malignancy is unclear

Before therapy:

CBC with renal and liver functional test, chest X-ray, TST (tuberculin skin test) and/or interferon gamma assays for ruling out TB, ruling out of infection and heart failure with NYHA class III–IV

During therapy:

CBC, renal and liver functional test, CRP, ESR every 14 days for the first month, then each month for the next 2 months and thereafter, if necessary

Pregnancy category B: discontinue at least 6 months prior to conception

[17, 30, 53, 69, 77]

Interferon

5.

Interferon

Antiviral, antiproliferative, antiangiogenic, and immunomodulatory effect;

blocking of IL-1 seems to enhance barrier function of retinal vessel endothelium

3 or 6 Mio IU/day subcutaneously (depending on indication and body weight; </> 55 kg)

BD:

6 mio IU/day for 2–4 weeks, then 4.5 mio IU/day for 2–4 weeks, then 3 mio IU/day for 1–3 months, then 3 mio IU every 2nd day for 1–3 months, then 3 mio IU 3×/week for 1–3 months, then 3 mio IU 2×/week for 1–3 months, then stop;

Macular edema:

3 mio IU/day for 1 months, then 3 mio IU every 2nd day for 2–3 months, then 3 mio IU every 3rd day for 3 months, then 3 mio IU every 4th day for 3v months and so on; evaluate lowest possible dose that maintains absence of CME

Within 2 weeks, if there is no onset of effect, the dosage can be increased up to 9 Mio/IU/day

Flu-like symptoms, mild leukopenia, alopecia, depression

Before therapy: CBC with differential blood count, liver functional test, and thyroid function tests, ruling out of depression, discontinuation of other immunosuppressives on the day before start of IFN-alpha, except corticosteroids (max. 10 mg/day)

During therapy: Premedication with paracetamol for flu-like symptoms (500 mg two to four times daily), CBC with differential blood count, liver functional test

Pregnancy category C

[10, 13, 14, 21, 28, 32–34, 37, 38, 42, 43, 47, 57, 58, 61, 62, 69, 71, 72, 74, 78]

Anti-CD20-blocking agent

6.

Rituximab

Chimeric monoclonal antibody against the CD20 antigen

Corticosteroid infusion prior to RTX;

two 1000 mg intravenous infusions in interval of 14 days or 375 mg/m² weekly for four consecutive weeks

Between 2 and 8 weeks, if there is no onset of effect after 16–24 weeks, the agent should be discontinued

Infusion reaction, infection, flu-like symptoms, temporary hyperuricemia

Before therapy:

Ruling out of infection (also hepatitis B) and heart failure with NYHA class IV

Pregnancy category C: discontinue at least 12 months prior to conception

[18, 30, 36, 44, 52, 60, 69]

Anti-CD80/86 receptor fusion protein

7.

Abatacept

Blocking of CD80/CD86 receptor on antigen-presenting cells preventing CD28 activation and thus inactivation of T cells

10 mg/kg intravenous infusion at 0, 2, and 4 weeks and every 4 weeks thereafter

After 3 months, if there is no onset of effect after 6 months, the agent should be discontinued

Gastrointestinal, central nervous disorders (headache, vertigo), infection, skin disorders (urticaria, herpes simplex), hypertension, hyperlipidemia, weight loss, fatigue

Before therapy:

Chest X-ray, TST (tuberculin skin test) and/or interferon gamma assays for ruling out of tuberculosis, ruling out of infection

During therapy:

CBC, renal and liver functional test, CRP, ESR every 14 days for the first month, then every 3 months

Pregnancy category C : discontinue at least 14 weeks prior to conception

[4, 27, 40, 69, 86]

Anti-IL-6 receptor antibody

8.

Tocilizumab

Blocking of both the membrane and the soluble IL-6 receptors

8 mg/kg body weight intravenous infusion every 28 days

After 4–6 weeks, if there is no onset of effect after 12 weeks, the agent should be discontinued

Gastrointestinal, elevated liver enzymes, central nervous disorders (headache, vertigo), skin disorders (exanthem, pruritus), hypertension, leukopenia, neutropenia, conjunctivitis

Before therapy:

Chest X-ray, TST (tuberculin skin test) and/or interferon gamma assays for ruling out of tuberculosis, ruling out of infection CBC, renal and liver functional test, lipid status

During therapy:

CBC, liver functional test, CRP, ESR before each infusion in first 3 months, then every 8 weeks, lipid status: 4–8 weeks after the start of therapy

Pregnancy category C: discontinue at least 3 months prior to conception

[2, 30, 69, 76]

Anti-IL-2 receptor antibody

9.

Daclizumab

Blocking of IL-2 receptor expressed on activated T cells

1 mg/kg intravenous every 2 weeks for 3 months, then every 3 weeks for 3 months, and monthly thereafter

After 3–10 weeks, if there is no onset of effect after 16–26 weeks, the agent should be discontinued

Gastrointestinal, edema extremities, pulmonary edema, central nervous disorders (headache, vertigo, tremor), infection, skin disorders (impaired wound healing, acne), hypersensitivity reaction, fatigue, musculoskeletal aches, hypertension, tachycardia, thrombosis, bleeding, lymphocele

Before each infusion: CBC with differential blood count, liver functional test, and urinalysis, then every 14 days for the first 3 months, then every 3 weeks for 3 months, and monthly thereafter

Pregnancy category C

[11, 15, 54, 55, 65, 73, 82, 84]