Updated: 12/22/2017

TNF-alpha Inhibitors

Topic
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Questions
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Evidence
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Overview

Snapshot
  • A 40-year-old woman presents to her physician’s office for management of her newly diagnosed rheumatoid arthritis. She reports that she has not tried any long-term medication for this disease and seeks advice. She is counseled on the immunosuppressive effects of this class of medications and is tested for latent tuberculosis prior to starting therapy.
Introduction
  • Tumor necrosis factor (TNF)-α inhibitors
    • categories
      • fusion proteins
      • monoclonal antibodies
  • Mechanism of action
    • inhibits physiologic response to TNFα, an important component of inflammation
  • Toxicity
    • immunosuppression
      •  risk of infections
      •  risk of lymphomas
    • reactivation of latent tuberculosis
      • TNF-α plays a key role in granuloma formation and stabilization
      • must always test for tuberculosis prior to starting TNF-α inhibitors
Fusion Proteins
  • Medications
    • etanercept
  • Mechanism of action
    • fusion protein of the receptor for TNFα and immunoglobulin (Ig) G1 Fc
      • produced by recombinant DNA
    • acts as a decoy TNFα receptor
  • Clinical use
    • ankylosing spondylitis
    • psoriasis
    • rheumatoid arthritis
  • Toxicity
    • immunosuppression
    • lupus-like syndrome
Monoclonal Antibodies
  • Medications
    • infliximab
    • adalimumab
    • certolizumab
    • golimumab
  • Mechanism of action
    • anti-TNFα monoclonal antibody
  • Clinical use
    • ankylosing spondylitis
    • hidradenitis suppurativa
    • inflammatory bowel disease
    • psoriasis
    • rheumatoid arthritis
  • Toxicity
    • immunosuppression
    • gastrointestinal irritation
 

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Questions (3)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.MK.75) A 43-year-old female presents with several years of pain and stiffness in her wrists and hands. Her symptoms have been getting progressively worse. She reports that her hands feel stiff for an hour or more after awaking in the morning. She undergoes subsequent testing, and is found to have anti-citrullinated protein antibodies. Her physician is concerned for rheumatoid arthritis, and discusses treatment with a biologic disease-modifying anti-rheumatic agent.

Which of the following must be done before beginning treatment with a TNF inhibitor? Review Topic

QID: 106868
1

Confirm diagnosis with a test for rheumatoid factor

6%

(7/110)

2

Confirm diagnosis with elevated ESR and CRP

6%

(7/110)

3

Test for latent mycobacterial infection

82%

(90/110)

4

Obtain a radiograph demonstrating osteophytes

0%

(0/110)

5

Obtain an exercise stress test

4%

(4/110)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M1.MK.201) A 36-year-old female presents with a 6-month history of stiffness in her joints. She reports bilateral knee pain that is worse in the morning prior to activity and stiffness of the fingers in both hands. Anti-CCP antibody tests are positive. Over several months, the patient's symptoms prove unresponsive to NSAIDs and methotrexate, and the decision is made to begin infliximab. Which of the following drugs has the most similar mechanism to inflixmab? Review Topic

QID: 106235
1

Imatinib

23%

(9/39)

2

Indomethacin

5%

(2/39)

3

Cyclophosphamide

5%

(2/39)

4

Trastuzumab

62%

(24/39)

5

Allopurinol

0%

(0/39)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 4
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