II. Background
- Most important agents in Rheumatoid Arthritis
- Start early (within 3 months of active disease onset)
- Response to these agents is slow over 1-6 months
- Consider tapering DMARD if in remission for at least 6 months (esp. if anti-citrullinated protein negative)
- In some cases DMARDs may be tapered off with maintained remission
- Haschka (2016) Ann Rheum Dis 75(1):45-51 [PubMed]
- Combination therapy may be optimal (often 3 agents, see below)
- Used with NSAIDs or COX2 Inhibitors
- Screening before starting biologic agents and immunosuppressants
- Tuberculosis Screening (PPD or IGRA)
- Hepatitis B Screening (HBsAg, HBcAb, HBsAb)
- Hepatitis C screening (anti-HCV)
- Skin malignancy (increased risk of Squamous Cell Skin Cancer, Melanoma)
- Update Vaccines prior to starting DMARDs if possible
- Avoid Live Vaccines (e.g. Flumist or Zostavax) while on DMARDs
- Influenza Vaccine
- Pneumococcal Vaccine
- Hepatitis B Vaccine
- HPV Vaccine
- Herpes Zoster Vaccine
III. Indications: Studies suggest starting DMARD early
- Early DMARD start results in better longterm outcomes with less Disability, joint destruction and higher remission rate
- Randomized trial of n=238 over 1 year follow-up
- Less Functional Disability in DMARD and NSAID
- Placebo group was NSAID alone
- No XRAY differences
- Van der heide (1996) Ann Intern Med 124(8): 699-707 +PMID: 8633829 [PubMed]
- Randomized trial of n=102 over 2 years of follow-up
- Triple Therapy Combination Management
- Methotrexate 7.5 to 17.5 mg each week
- Sulfasalazine 500 mg PO bid
- Hydroxychloroquine sulfate (Plaquenil) 200 mg bid
- Good response (>50% improvement)
- Patients on triple therapy: 77% response
- Patients on 1 to 2 drugs: 33-40% response
- As effective as Methotrexate with biologic DMARD (Monoclonal Antibody or TNF agents)
- Drug toxicity
- Medications discontinued in 10% patients on 3 drugs
- References
- Triple Therapy Combination Management
IV. Protocol: Choice of intial agent
- First-line agent
- Other agents if higher risk of hepatotoxicity (e.g. pre-existing liver disease, Alcohol Abuse)
V. Preparations: First line in moderate to severe disease
-
Methotrexate
- Dosing
- Start: Methotrexate 10-15 mg orally once weekly
- Advance as needed up to 20 mg orally once weekly
- Coadminister with Folic Acid 1 mg orally daily (or 5 mg once weekly) to reduce side effects
- If gastrointestinal side effects limit use:
- Divide oral dose into 2 doses, 12 hours apart
- Methotrexate SQ/IM (vial $20/month or autoinjector $600/month)
- Efficacy
- Most effective single DMARD
- Good benefit to risk ratio
- Superior effect with Plaquenil or Sulfasalazine
- Methotrexate and
- Hydroxychloroquine sulfate (Plaquenil) and
- Sulfasalazine (may be used in place of Plaquenil)
- Combination with Etanercept reverses joint damage
- Dosing
-
Leflunomide (Arava)
- Dose: 10-20 mg orally weekly
- Alternative to Methotrexate (and now generic)
VI. Preparations: Second line (First line if mild disease)
- Hydroxychloroquine (Plaquenil) 100-200 mg orally twice daily
- Sulfasalazine (Azulfidine) 500 mg orally bid to tid
-
Minocycline 100 mg PO bid
- Modest effect
- May work best early
VII. Preparations: Third Line Agents (biologics in refractory cases)
- Precautions
- Do not start without an initial trial on Methotrexate (or similar DMARD) first
- Anti-Tumor Necrosis Factor Medications (see below)
- Advantages: Highly effective in refractory cases
- Disadvantages: Costs exceed $15,000 per year
- Containdicated in Congestive Heart Failure, skin malignancy
- Screen for Tuberculosis and Viral Hepatitis before starting (see above)
- Anti-TNF Agents
- Adalimumab (Humira)
- Etanercept (Enbrel)
- Infliximab (Remicade)
- Certolizumab (Cimzia)
- Golimumab (Simponi)
- Other biologic agents
- Interleukin-1 Receptor Antagonist
- Interleukin-6 Receptor Antagonist
- Anti-CD20
- Costimulator blocker (Cytotoxic T-CellAntigen 4)
- Abatacept (Orencia)
- Janus Kinase Inhibitor (JAK Inhibitor)
- Tofacitinib (Xeljanz)
- Increased risk of Thromboembolism
VIII. Preparations: Corticosteroids
- Indications
- Consider for severe symptoms when starting DMARD
- Symptoms refractory to above
- More cost-effective than NSAID with prophylaxis (PPI)
- Preparations
- Intra-articular Corticosteroid
- Prednisone 5-10 mg orally daily for 4-6 weeks
IX. Preparations: Last ditch effort (more serious adverse effects)
- D-Penicillamine
- Cyclophosphamide (Cytoxan)
- Effective for Vasculitis
-
Azathioprine (Imuran) 50 to 150 mg PO qd
- Slow onset
- Reasonably effective
X. Preparations: Rarely used due to decreased efficacy (historical)
- Parenteral Gold (Solganal)
- Slow onset
- Decreases progression but rarely remits
- Rarely used now
-
Oral Gold (Auranofin)
- Rarely used now due to decreased efficacy
- Staphylococcal Protein A Column (Prosorba)
- No longer available as of 2006
- Plasma filtering device with immunomodulatory effect via IgG binding
- Had been used in refractory RA at $1000 per column, performed weekly
- Felson (1999) Arthritis Rheum 42:2153-59 [PubMed]
XI. Monitoring
- All agents above need careful monitoring
- Lab Tests every 4-8 weeks
- Liver Function Tests
- Complete Blood Count
- Serum chemistry panel (Chem7)
- Physical Exam 3-6 times per year
XII. References
- (2014) Presc Lett 21(10): 56
- Boers (1997) Lancet 350: 309-18 [PubMed]
- Stein (1997) Arthritis Rheum 40: 1721-3 [PubMed]
- Rozman (1998) J Rheumatol 53:27-32 [PubMed]
- Moreland (1998) Rheum Dis Clin North Am 24: 579-91 [PubMed]
- Pincus (1993) Rheum Dis Clin North Am 19:123-151 [PubMed]
- Scott (2010) Lancet 376(9746):1094-108 [PubMed]
- Wasserman (2011) Am Fam Physician 84(11): 1245-52 [PubMed]
- Wasserman (2018) Am Fam Physician 97(7): 455-62 [PubMed]
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Definition (CSP) | agent that relieves or prevents rheumatic disease, especially rheumatoid arthritis. |
Definition (MSH) | Drugs that are used to treat RHEUMATOID ARTHRITIS. |
Concepts | Pharmacologic Substance (T121) |
MSH | D018501 |
SnomedCT | 88279005, 372888006 |
English | Agents, Anti-Rheumatic, Anti-Rheumatic Agents, antirheumatic agent, Agents, Antirheumatic, Anti Rheumatic Drugs, Anti-Rheumatic Drugs, Antirheumatic Agents, Antirheumatic Drugs, Drugs, Anti-Rheumatic, Drugs, Antirheumatic, ANTIRHEUMATICS, Antirheumatic Agent, Antirheumatic, Antirheumatic Agent [TC], [MS100] ANTIRHEUMATICS, antirheumatic agents, antirheumatic, anti rheumatic drug, anti-rheumatic drugs, anti rheumatic drugs, antirheumatic drugs, antirheumatic drug, antirheumatics, Anti Rheumatic Agents, Antirheumatic agents, Anti-rheumatic agent (product), Anti-rheumatic agent (substance), Anti-rheumatic agent, Anti-rheumatic agent, NOS |
Swedish | Antireumatiska medel |
Czech | antirevmatika |
Finnish | Reumalääkkeet |
Italian | Farmaci antireumatici, Antireumatici |
Russian | PROTIVOVOSPALITEL'NYE SREDSTVA ZOLOTOSODERZHASHCHIE, PROTIVOREVMATICHESKIE SREDSTVA, ANTIREVMATICHESKIE SREDSTVA ZOLOTOSODERZHASHCHIE, BOLEZN'-SMIAGCHAIUSHCHIE ANTIREVMATICHESKIE LEKARSTVENNYE SREDSTVA, ANTIREVMATICHESKIE SREDSTVA, KHRIZOTERAPEVTICHESKIE SREDSTVA, ANTIREVMATICHESKIE LEKARSTVA, SMIAGCHAIUSHCHIE TECHENIE BOLEZNI, PROTIVOREVMATICHESKIE SREDSTVA ZOLOTOSODERZHASHCHIE, ZOLOTOSODERZHASHCHIE PROTIVOVOSPALITEL'NYE SREDSTVA, DMARD, АНТИРЕВМАТИЧЕСКИЕ ЛЕКАРСТВА, СМЯГЧАЮЩИЕ ТЕЧЕНИЕ БОЛЕЗНИ, АНТИРЕВМАТИЧЕСКИЕ СРЕДСТВА, БОЛЕЗНЬ-СМЯГЧАЮЩИЕ АНТИРЕВМАТИЧЕСКИЕ ЛЕКАРСТВЕННЫЕ СРЕДСТВА, ПРОТИВОРЕВМАТИЧЕСКИЕ СРЕДСТВА, АНТИРЕВМАТИЧЕСКИЕ СРЕДСТВА ЗОЛОТОСОДЕРЖАЩИЕ, ЗОЛОТОСОДЕРЖАЩИЕ ПРОТИВОВОСПАЛИТЕЛЬНЫЕ СРЕДСТВА, ПРОТИВОВОСПАЛИТЕЛЬНЫЕ СРЕДСТВА ЗОЛОТОСОДЕРЖАЩИЕ, ПРОТИВОРЕВМАТИЧЕСКИЕ СРЕДСТВА ЗОЛОТОСОДЕРЖАЩИЕ, ХРИЗОТЕРАПЕВТИЧЕСКИЕ СРЕДСТВА |
Japanese | 疾病-修飾抗リウマチ薬, 抗リウマチ剤, 疾病-修飾第二線薬, 抗リウマチ薬 |
Croatian | Not Translated[Antirheumatic Agents] |
Polish | Leki przeciwreumatyczne, Leki przeciwreumatyczne modyfikujące chorobę, Leki zmieniające przebieg choroby |
Spanish | Antirreumáticos, Drogas Antirreumáticas Modificadoras de la Enfermedad, Agentes Antirreumáticos, agente antirreumático (producto), agente antirreumático (sustancia), agente antirreumático, antirreumático |
Norwegian | Antirevmatiske midler, DMARD, Antirevmatika |
Portuguese | Antirreumáticos, Drogas Modificadoras da Evolução de Doenças Reumáticas, Agentes Antirreumáticos |
French | Agents antirhumatismaux, Antirhumatismaux, Agent antirhumatismal, Antirhumatismal, Médicaments antirhumatismaux |
German | Antirheumatika, Rheumamittel |