Traditional DMARDs

Methotrexate

**MOA: **Inhibition of purine and pyrimidine synthesis (folic acid mimic)

SEs

• Bone marrow suppression
• N / V / D
• Stomatitis / mucositis
• Hepatic Cirrhosis
• Hepatitis
• Hepatic Fibrosis
• Pneumonitis
• Pulmonary Fibrosis
• Rash
• Urticaria
• Alopecia
• Teratogenicity
• Bone marrow suppression, N / V / D, and stomatitis / mucositis may be improved with folate 1mg QD

CIs

• Pregnancy
• Lactating
• Chronic liver disease
  • Caution w/ chronic EtOH use
• Immunodeficiency
• Existing blood dyscrasias
• Pleural or peritoneal effusion
• CrCl < 40

Monitoring

• Baseline
  • CXR
  • CBC w/ Plt
  • SCr
  • Full Hepatic Panel
  • Hep B & C Screening
• Maintenance: CBC, SCr, LFT
  • < 3mo from initiation: q2-4wks
  • 3-6mo: q8-12wks
  • > 6mo: q12wks

Leflunomide

**MOA: **Prodrug inhibitor of pyrimidine synthesis via dihydroorotate dehydrogenase, leading to inhibition of T-cell proliferation

SEs

• Diarrhea
• Rash
• Alopecia
• Increased LFTs
• Teratogenic in both males and females
  • Use cholestyramine 8g TID x11d to clear for conception

CIs

• Pregnancy

Monitoring

• Baseline
  • CBC
  • SCr
  • LFTs
• Maintenance: Same as MTX

Hydroxychloroquine

**MOA: **Inhibition of protein secretion by lysosomal accumulation

SEs

• N / V / D
• Increased skin pigmentation
• Rash
• Alopecia
• Retinal Toxicity
  • Avoid in pts > 70yo
  • Avoid cumulative lifetime dose > 800g

Monitoring

• Vision exam at baseline and q6-12mo

Sulfasalazine

**MOA: **Prodrug that surpasses cytokine release from macrophages via an unknown mechanism

SEs

• N / V / D
• Anorexia
• Rash
• Urticaria
• Photosensitivity
• Sulfa Allergy
• Leukopenia
• Thrombocytopenia
• Rare Hematologic SEs
  • Aplastic Anemia
  • Hemolytic anemia

Monitoring

• Baseline
  • LFTs
  • CBC
  • SCr
• Maintenance: Same as MTX

TNF Antagonists

Agents

• Etanercept (Enbrel)
• Infliximab (Remicade)
• Adalimumab (Humira)
• Golimumab (Simponi)
• Certolizumab (Cimzia)

SEs

• HA
• Rash
• URIs
• Injection site reaction
• CHF exacerbation
• Risk of malignancy
• Risk of demyelinating disease

Precautions / Warnings

• Increased risk of infection
• Not for use w/ anakinra due to increased infection risk
• Demyelinating disorders
• Malignancies
• CHF
• No concurrent live vaccines

CIs

• See precautions for class above

Monitoring

• TB skin test before starting therapy

Golimumab

Monitoring

• CBC w/ Plt
• LFTs

IL-1 Receptor Antagonists

Anakinra (Kineret)

SEs

• Injection site reaction
• HA
• N / V
• Flu-like SSx
• Hypersentivity to E. coli derived proteins
• Increased risk of serious infections
• Neutropenia

Warning / Precation

• Do not use w/ TNF inhibitors or abatacept due to infection risk

Monitoring

• Neutrophil count at baseline, monthly x3mo, then q3mo x1yr

Anti-CD20 Ig

Rituximab (Rituxan)

MOA: Binds CD20 on B cells and activates NK cells against B cells, leading to apoptosis

SEs

• T umor lysis syndrome
• Mucocutaneous reactions
• Viral infection
• Hypersensitivity
• Renal toxicity
• Bowel obstruction
• Hepatitis B reactivation
• Cardiac arrhythmia

Warnings

• Black Box: Fatal infusion reaction, tumor lysis syndrome, and mucocutaneous reactions

Monitoring

• CBC w/ plts
• SCr
• Vital signs during infusion

CTLA-4 Antagonist

Abatacept (Orencia)

MOA: Inhibits co-stimulatory signal by binding to CTLA-4 on T_C cells

SEs

• HA
• Nausea
• URI
• Nasopharyngitis
• Infusion reaction
• Serious infeciton
• Malignancy

Warning / Precautions

• Caution in COPD due to infection risk
• No live vaccinations
• Not for use w/ TNF inhibitors or IL-1 antagonists

Monitoring

• No hematologic monitoring

IL-6 Inhibitor

Tocilizumab (Actrema)

SEs

• Serious infection
• Hepatotoxicity
• Thrombocytopenia
• Neutropenia
• Infusion reactions
• Lipid abnormalities
• Intestinal perforation

Warnings

• Black Box: Serious infection

CIs

• Liver toxicity
• Thrombocytopenia
• Neutropenia

Monitoring

• Neutrophil Count q4-8wks
• Plt Count q4-8wks
• LFTs q4-8wks
• Lipid Panel: After 4-8wks then q6mo

Janus Kinase Inhibitors

Tofacitinib (Xeljanz)

SEs

• URI
• HA
• Diarrhea
• Nasopharyngitis

Warnings / Precautions

• CYP Interactions
• Do not use w/ hepatic impairment
• Black Box: Risk of infection and malignancy

CIs

• Hgb < 9
• ANC < 1000
• Lymphocyte Count < 500

Monitoring

• Lymphocyte Count at baseline then q3mo
• Neutrophil count at baseline, 4-8wks, then q3mo
• Hgb at baseline, 4-8wks, then q3mo