Chapter 46 - Systemic Steroids and Autoimmune Conditions

Systemic Steroids

What are long-term effects of steroids

Glaucoma, cataracts, fat deposits in face, pink-purple marks on abdomen, thighs, breasts and arms (skin the bruises easily), growth retardation, infection and impaired wound healing, psychiatric changes, GI bleeding/esophagitis/ulcers, diabetes, hair growth on face and body as well as irregular menstrual periods

What is the systemic steroids (PO, IV) dose equivalency

Cortisone 25mg

Hydrocortisone (Solu Cortef) 20mg

Prednisone (Deltasone) 5mg

Prednisolone (Millipred, Orapred ODT) 5mg

Methylprednisolone (Medrol, Solu-Medrol) 4mg

Triamcinolone (Kenalog) 4mg

Dexamethasone (Decadron) 0.75mg

Betamethasone 0.6mg

What are some safety/side effects/monitoring information about systemic steroids?

Warnings: Adrenal suppression, must taper slowly

S/E used <1 month: Fluid retention, stomach upset, emotional instability, insomnia, increase appetite, weight gain, acute increase in blood glucose/pressure

Immunosuppression From Steroids tip

A patient is immunosuppressed when using ≥2mg/kg/day or ≥20mg/day of prednisone or prednisone equivalent. Avoid live vaccines due to a high risk of infection and taper when discounting steroids due to HPA axis suppression.

Rheumatoid Arthritis

What are some classic articular symptoms of RA?

Joint swelling, pain, stiffness, bone deformity

What are examples of traditional (non-biologic) disease-modifying antirheumatic drugs (DMARDs)?

Methotrexate (Trexall)

Hydroxychloroquine (Plaquenil)

Sulfasalazine (Azulfidine)

Leflunomide (Arava)

JAK inhibitors

Methotrexate brand name

Trexall

Hydroxychloroquine brand name

Plaquenil

Sulfasalazine brand name

Azulfidine

Leflunomide brand name

Arava

Methotrexate drug info

Dosing: 7.5 to 20mg once weekly

Boxed Warning: Hepatotoxicity, myelosuppresion, mucositis, stomatitis, pregnancy (teratogenic)

Monitoring: CBC and LFTs, chest X-ray, hepatitis B and C serologies

Notes: Folate can be given to decrease hematological, GI and hepatic side effects: give 5mg PO weekly on the day following MTX

Hydroxychloroquine drug info

Warnings: Irreversible retinopathy, QT prolongation

Side Effects: Vision changes

Monitoring: Eye exam

Sulfasalazine drug info

Contraindication: Patients with sulfa or salicylate allergy

Notes: Can cause yellow-orange coloration of skin/urine

Leflunomide drug info

Boxed warnings: Do not use in pregnancy (teratogenic), hepatotoxicity

Notes: Accelerated drug elimination options:

Can do cholestyramine or activated charcoal suspension. Must have negative pregnancy test prior and use 2 forms of birth control during treatment. If pregnancy is desired, must wait 2 years after discontinuation or use accelerated drug elimination procedure

What are examples of JAK inhibitors

Tofacitinib (Xelijanz)

Baricitinib (Olumiant)

Upadacitinib (Rinvoq)

(-citinib)

What are safety/side effects/monitoring parameters for JAK inhibitors in RA?

Boxed warnings: Serious infections including TB, fungal, viral, bacterial or other serious opportunistic infections. Malignancy and thrombosis as well.

Do not use with biologic DMARDs or potent immunosuppressants

What are Methotrexate drug interactions?

MTX should not be taken with alcohol due to an increase risk of liver toxicity

Renal elimination is decreased by aspirin/NSAIDs, resulting in MTX toxicity

What are examples of tumor necrosis factor alpha inhibitors? Anti-TNF Biologics

Entanercept (Enbrel)

Adalimumab (Humira)

Infliximab (Remicade)

Certolizumab pegol (Cimzia)

Golimumab (Simponi)

Entanercept brand name

Enbrel

Adalimumab brand name

Humira

Infliximab brand name

Remicade

Certolizumab pegol brand name

Cimzia

Golimumab brand name

Simponi

Dosing for Etanercept (Enbrel)

50 mg SC weekly

± MTX

Dosing for Adalimumab (Humira)

40mg SC every other week

± MTX

Dosing for Infliximab (Remicade)

3mg/kg IV at weeks 0, 2, and 6, then every 8 weeks

+MTX

Dosing for certolizumab pegol (Cimzia)

400mg SC at weeks 0, 2, and 4, then 200 mg SC every other week

± MTX

Dosing for Golimumab (Simponi)

SC 50mg monthly

There is an IV formulation and that requires a filter

+MTX

What are safety/side effects/monitoring parameters of Anti-TNF Biologics in RA?

Boxed Warnings: Serious infections including TB, fungal, viral, bacterial, or opportunistic: screen for latent TB. Lymphomas and malignancies

Warnings: Demyelinating disease, hepatitis B reactivation, heart failure, hepatotoxicity, lupus-like syndrome

Monitoring: TB test and treat if positive before starting therapy; test for HBV. Routine screen for signs of infection

Notes: Do not shake or frezee; require refrigeration. MTX is used 1st line and these are add-on therapy. Can be initial therapy if severe

What are examples of other biologics (Non-TNF inhibitors)?

Rituximab (Rituxan)

Anakinra (Kineret)

Abatacept (Orencia)

Tocilizumab (Actemra)

Sarilumab (Kevzara)

Rituximab brand name

Rituxan

Anakinra brand name

Kineret

Abatacept brand name

Orencia

Tocilizumab brand name

Actemra

Sarilumab brand name

Kevzara

Rituximab (Rituxan) drug information

Premedicate with a steroid, acetaminophen, and an antihistamine

Boxed warnings: Infusion-related reactions, HBV reactivation; screen for high-risk groups for HBV and HCV

Anakinra (Kineret) drug information

Warnings: Malignancies and serious infections

Systemic Lupus Erythematosus

What group of people does SLE predominately occur in?

Individuals 15-45 years old and more common in women of African-American and Asian decent.

What are clinical presentations of SLE?

flat, red rash on their face, across the nose bridge and cheeks. This is called a malar rash, commonly known as a butterfly rash because of its shape.

What are select drugs that can cause drug-induced lupus erythematosus (DILE)?

Methimazole, Propylthiouriacil, Methyldopa, Minocycline, Procainamide, Hydralazine, Anti-TNF agents, Terbinafine, Isoniazide, Quinidine

What is some non-drug treatment for SLE?

Photosensitivity is common in SLE, sunscreens and sun protection/avoidance are required

What are some agents that can help control SLE?

Hydroxychloroquine, cyclophosphamide, azathioprine, mycophenolate mofetil, and cyclosporine (options for chronic care)

What drugs are approved for the treatment of SLE?

Belimumab (Benlysta) (for tx of lupus and lupus nephritis)

Voclosporin (Lupkynis) (for tx of only lupus nephritis)

Multiple Sclerosis

What is multiple sclerosis (MS)?

It is a chronic, progressive autoimmune disease in which the patient’s immune system attacks the myelin sheath.

What are symptoms of MS?

Early symptoms: Fatigue, numbness, and blurred vision

As condition worsens: cognitive decline, muscle spasms, pain, bladder spasticity, difficulty walking with gait instability

Glatiramer acetate (copaxone) drug information for MS

An immune modulator thought to induce and activate T-lymphocyte suppressor cells in relapsing forms of MS

Dosing: 20mg SC qd or 40mg SC 3 times per week

Warning: Chest pain

S/Es: Injection site reactions, flushing, diaphoresis, dyspnea

Notes: Preferred agent is tx necessary during pregnancy

What are examples of interferon beta products with dosing?

Interferon beta-1a

Avonex: 30mcg IM weekly

Rebif: 22mcg or 44mcg SC three times per week

Interferon beta-1b (Betaseron, Extavia) 0.25 mg SC every other day

Peginterferon beta-1a (Plegridy) 63mcg SC on day 1, 94mcg SC on day 15, then 125mcg SC every 14 days starting on day 29

Safety/side effects/monitoring parameters of Interferon beta products

Warning: Psychiatric disorders, injection site necrosis, increase LFTs, thyroid dysfunction (hyper or hypo)

Notes: If refrigerated, let stand at room temperature prior to injection. Do not expel the small air bubble in prefilled syringes due to loss of dose. Some formulations contain albumin which can increase risk of Creutzfeldt-Jakob disease transmission (rare)

What are examples of Sphingosine 1-phosphate (S1P) receptor modulators for MS?

Fingolimod (Gilenya)

Ozanimod (Zeposia)

Ponesimod (Ponvory)

Siponimod (Mayzent)

What are safety/side effects/monitoring for S1P receptor modulators?

Contraindications: For Ozanimod severe untreated sleep apnea or concomitant use of an MAO inhibitor. Then for Siponimod CYP2C9 3/3 genotype

Warnings: Slow HR, monitored for at least 6 hours after the first dose (ECG required). Increase risk for infection (monitor CBC), screen for VZV. Macular edema (monitor with eye exams), hepatotoxicity (monitor LFTs)

Notes: MS can become much worse when treatment is stopped

What are examples of fumarates or nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activators in MS?

Dimethyl fumarate (Tecfidera)

Diroximel fumarate (Vumerity)

Monomethyl fumarate (Bafiertam)

What is one important counseling point for NrF2 activator agents?

Do not crush, chew, or sprinkle capsule contents on food

Drug information on Teriflunomide (Aubagio)?

It is a pyrimidine synthesis inhibitor

Severe hepatotoxicity and teratogenicity, can use accelerated elimination (same as leflunomide)

What are examples of CD20-directed monoclonal antibodies for MS?

Ofatumumab (Kesimpta)

Ubiltuximab (Briumvi)

Ocrelizumab (Ocrevus)

Other monoclonal antibodies (other than CD20)?

Alemtuzumab (Lemtrada) - REMS program required

Natalizumab (Tysabril) - Progressive multifocal leukoencephlopathy (PML) contraindication

Raynaud’s Phenomenon

What is Raynaud’s phenomenon?

Common condition that is triggered by exposure to cold and/or stress, leading to vasospasms in extremities (most commonly first in fingers and/or toes)

What drug is the most commonly used prevention agent for Raynaud’s?

Nifedipine

What are drugs that can cause or worsen Raynaud’s?

Beta blockers, bleomycin, cisplatin, sympathomimetics such as amphetamines, pseudoephedrine, and illicit drugs

If a patient has celiac disease what is the key word to look for on package inserts?

Starch

Myasthenia Gravis

What is Myasthenia Gravis?

Autoimmune condition that attacks the connections between nerves and muscles, often leading to weakness in the muscles that control the yes, face, neck, and limbs

What are drugs that can worsen myasthenia gravis?

Select antibiotics, magnesium salts, select antiarrythmics, beta blockers and calcium channel blockers, select antipsychotics, muscle relaxants, botulinum toxin

What is the treatment for Myasthenia Gravis?

Pyridostigmine (Mestinon)

warning: Has cholinergic effects

Sjogren’s Syndrome

What is Sjogren’s Syndrome?

It is an autoimmune disease most often characterized by severe dry eyes and dry mouth.

What is drug treatment for dry eyes in sjogren’s syndrome?

Popular OTC artificial teardrops available are Systane, Refresh, Clear Eyes, Liquifilm

Prescription include cyclosporine eye drops (Restasis) or can even use Lifeitegrast (Xiidra)

What is drug treatment for dry mouth in sjogren’s syndrome?

Sugar-free chewing gum or lozenges. Rinse daily with antimicrobial mouthwash.

Or can use prescription Pilocarpine which is a muscarinic agonist

Psoriasis

What is psoriasis?

Autoimmune disease that appears on the skin. Most common is plaque psoriasis, which appears as raised, red patches covered with a slivery-white buildup.

What is non-drug treatment for psoriasis?

Ultraviolet (UV) light exposure which causes activated T-cells in the skin to die

Examples of topical drug treatment for psoriasis?

Steroids, coal tar products (they are messy), tazarotene, anthralin, calcipotriene, and tapinarof

Examples of systemic psoriasis treatment?

Acitretin, Apremilast, monoclonal antibodies, deucravacitinib