chapter 76: drug therapy of rheumatoid arthritis

main tx for RA

• relieve symptoms

• maintain joint function

• minimize systemic involvement

• delay progression of disease

• nondrug measures

DMARDs

• disease modifying antirheumatic drugs

• conventional DMARDs (traditional)

• biologic DMARDs

first generation NSAIDs

Inhibit COX-1( can cause gastric issues/ gi bleeds) and COX-2( cardio issues) 

2nd generation NSAIDs

Selectively inhibit COX-2 (Celecoxib)

safety of NSAIDs

All prescription-strength NSAIDs carry a boxed warning regarding risk of thrombotic events and gastrointestinal (GI) ulceration and bleeding ( example aspirin: it inhibits platelet aggregation) 

glucocorticoids for RA

use oral glucocorticoids for generalized symptoms

use intraarticular injections if one or two joints are affected

use prednisone or prednisolone for inflammation (mostly used for autoimmune things)

Methotrexate indication

• Most rapid-acting DMARD

• Therapeutic effect: 3 to 6 weeks

adverse effects for methotrexate

• Hepatic fibrosis

• Bone marrow suppression

• GI ulceration

• Pneumonitis

It is very teratogenic!!!

Leflunomide indications

• Powerful immunosuppressant for adults with active RA

• Anti-inflammatory and immunomodulatory actions

• Can decrease signs and symptoms and slow disease progress

• Reserved for second line use

major conventional DMARDs

• Leflunomide [Arava]

• Hydroxychloroquine [Plaquenil]

• Minocycline [Minocin]

• Penicillamine

• Azathioprine [Imuran]

• Cyclosporine

• Prosorba column

major biologic DMARDs MOA + adverse effects

• Tumor necrosis factor (TNF) inhibitors

• Suppress immune function

• Pose risk of serious infection (adverse effect)

• Work by neutralizing TNF

biologic DMARDs examples

• Etanercept [Enbrel]

• Adalimumab [Humira]

• Certolizumab pegol [Cimzia]

• Golimumab [Simponi]

• Golimumab [Simponi Aria]

• Infliximab [Remicade]

Etanercept MOA

inactivates TNF

Etanercept indication

moderate to severe RA

adverse effects of etanercept

• serious infections

• severe allergic rxns

• HF

• hematologic disorders

• liver injury

• CNS demyelinating disorders

etanercept drug interactions

TNF

MOA/ indications of Rituximab [Rituxan]

reduces the number of B lymphocytes

reduces symptoms of RA and slows disease progression

adverse effects of Rituximab [Rituxan]

Infusion reactions, monocutaneous reactions, hepatitis B reactivation, progressive multifocal leukoencephalopathy (PML), others

MOA/ indication for Abatacept [Orencia]

• First-in-class T-cell activation inhibitor

• Reduces symptoms of RA and disease progression

adverse effects for Abatacept [Orencia]

Headache, upper respiratory infection, nasopharyngitis, nausea, serious infections

interactions for Abatacept [Orencia]

vaccines

MOA for Tocilizumab

• Interleukin-6 (IL-6) receptor antagonist

• Monoclonal antibody

MOA for Tocilizumab

Blocks receptors for IL-6, a proinflammatory cytokine that helps mediate the autoimmune attack against the joints of patients with RA

adverse effects for Tocilizumab

Serious infections, GI perforation, liver injury, neutropenia, thrombocytopenia

MOA/ adverse effect for Anakinra (Kineret)

• Blocks receptors for interleukin-1, a proinflammatory cytokine that plays a central role in synovial inflammation and joint destruction

• Risk of serious infection