Application of biological agents in rheumatism and immunology

What is a biological agent

Refers to preparations produced or extracted from antibodies, enzymes, hormones or other biological sources
.

The biological preparations currently on the market that are used in rheumatism immunity are:

Targets of action-TNFα: Etanercept (enaciprecept), Infiximab (infliximab), Adalimumab (Adalimumab), Golimumab (Golimumab), Certolizumab ( Certuzumab)
.

Targets of action-IL-1: Anakinra (Ambiol), Rilonacept (rilocept), IL-6: Toclizumab (tocilizumab)

Target of action-B cells: Belimumab, Rituximab, Ofatumumab, Ocerelizumab

Target of action-T cells: Abatacept (Abatacept)

Classification and characteristics of biological agents

Tumor Necrosis Factor Inhibitors:

1) Etanercept (Etanercept, Yisaipu, Enli): Dimer fusion protein : human TNF receptor is connected to the FC part of human IgG1, which binds to soluble and cell model TNF, preventing TNF from TNF on the cell surface Receptor binding
.

2) Inflixi (like gram): anti-TNF mouse/human chimeric monoclonal antibody, which binds to soluble and cell model TNF and prevents TNF from binding to cell surface receptors
.

3) Adamu (Humira): Human monoclonal antibody against TNF , which binds to soluble and cell model TNF and prevents TNF from binding to cell surface receptors
.

Clinical application of biological agents

1.
Mandatory spondylitis

Recommended usage:

Inacipr: 25mg, twice a week, subcutaneously

Inflixide: 5mg/kg, instilled every 2, 4, 8 weeks after the first infusion, and every 8 weeks thereafter, intravenous infusion, dissolved in 250-500mlNS, infusion time is not less than 2 Hour Adalimumab: 40mg, once every 2 weeks, subcutaneous injection

2.
Clinical application:

A large number of clinical trials at home and abroad have confirmed that TNF inhibitors have a good effect on AS, not only can better control the inflammation, but also have long-term use.

Can delay or even improve bone destruction
.

3.
Clinical indications:

①Patients poorly treated with traditional medicines;

②Those who cannot tolerate traditional medicines;

③Patients with joint damage (especially hip joint);

④Severe active inflammation, such as severe peripheral joint swelling and pain, bright

Obvious lumbosacral stiffness, etc.
, and economic conditions permit
.

Note: Due to consideration of patients' affordability and drug side effects, we have improved the usage of TNF inhibitors: reduce the dosage and use density
.

  For example: Inacipu is changed to once a week, or even once every two weeks, the longest one is once a month
.

  Cut the dose of inflixil in some patients by half
.

Rheumatoid Arthritis

(1) Recommended usage

Inacipr: 25 mg twice a week, subcutaneously

Inflixil: 3 mg/kg, instilled every 2, 4, 8 weeks after the first infusion, and once every 8 weeks thereafter, intravenous infusion, dissolved in 250-500 ml NS, the infusion time is not Less than 2 hours
.

Adalimumab: 40 mg, once every 2 weeks, subcutaneously

(2) Clinical application

A large number of clinical trials and use have confirmed that TNF inhibitors have a good effect on RA, not only can better control the performance of joint inflammation, but also long-term use (over 6 months) may delay or even improve bone destruction
.

2.
Indications:

① Those whose condition cannot be controlled by traditional combination therapy with MTX as the mainstay
.

②The disease progresses rapidly, with bone destruction in the early stage
.

③Patients with high disease activity and risk factors for developing progressive RA:

       a) The number of joints involved during disease activity>20

       b) Rheumatoid nodules, especially those with multiple numbers

       c) High titer RF or anti-CCP antibody (+)

       d) Continuous increase in erythrocyte sedimentation rate, CRP and blood eosinophils

       e) Imaging bone erosion manifestations

④ Early active patients who can afford it
.

 Note: ① TNF inhibitors must be combined with immunosuppressive agents such as MTX to better control the RA condition, which is different from AS
.

      ②For Inflix, combined with MTX can also reduce the production of human anti-chimera antibodies and reduce drug resistance
.

Psoriatic arthritis

      (1) Traditional treatment is mainly based on a larger dose of MTX (15-25mg/w), which has larger side effects
.

      (2) TNF inhibitors not only have a significant effect on arthritis, but also have a good effect on skin rash and ophthalmia
.

Reactive arthritis and undifferentiated spondyloarthropathy

      (1) Average reactive arthritis and undifferentiated spondyloarthropathy used to control NSAID, small doses of hormones, MTX and the like
.

      (2) TNF inhibitors can be used for refractory cases, which can not only control the condition well, but also reduce or shorten the dose and treatment course of hormones and MTX
.

      (3) In reactive arthritis and undifferentiated spondyloarthropathies, inaercept seems to be more suitable than inflix
.

Contraindications and countermeasures of using TNF inhibitors

(1) During active infection

Countermeasures: TNF inhibitors are not suitable for severe infections, and can be used after the infection is cured; it is not recommended for patients with hepatitis B, but there is no evidence that the use of hepatitis C patients will increase hepatitis and viral load; for tuberculosis, first respond to all patients before treatment For TB screening , patients with active tuberculosis should be adequately treated; patients who have had tumors should be used with caution.
If the tumor has not recurred in 10 years, it is not a contraindication to TNF therapy, but it should be used with caution for those with precancerous lesions
.

(2) In the last 12 months, septic arthritis of the proper joint or sepsis of the artificial joint occurred
.

(3) Congestive heart failure grade 3 or 4 (NYHA standard)

Countermeasures: Patients with grade 3-4 heart failure should not be treated with anti-TNF therapy, and patients with mild heart failure should be cautious
.

(4) Pregnant women or breastfeeding women

Although animal experiments have not found that anti-TNF therapy has the risk of teratogenicity or miscarriage, it is still unclear for humans
.

(5) A clear history of demyelination

People with a clear or suspicious history of demyelinating disease and a clear family history of demyelinating disease should avoid using it; if demyelinating disease manifestations occur during treatment, anti-TNF therapy should be stopped and a neurologist should be asked for treatment