
Nicole Droz, MD
How do rheumatologists choose treatments for their patients? What are the differences between generic, brand names and biosimilars? How are the treatments administered? What are the common side effects for the most frequently prescribed medications?
Choosing a Medication
Every patient with RA is unique. Treatment options are individualized based on multiple factors including severity of disease, other medical problems, lifestyle factors and the desire to become pregnant amongst others. In general, we tend to start with a traditional Disease Modifying Anti-Rheumatic Drug (DMARD), such as methotrexate, before moving on to biologic therapies.
DMARDs may be given alone or in combination with another DMARD or biologic. Biologics are never given together due to risk of infectious complications.
Differences between Brand Names, Generics and Biosimilars
Brand Names vs. Generics
We do have generic versions of our DMARD medications. The FDA follows a rigorous review and monitoring process for generic medications to ensure they have the same safety, efficacy and quality as brand name medications. The active ingredients are identical, however, inactive ingredients may differ and can cause side effects in some patients. The generic medications may look different than the brand name and often come with significant cost advantages.
Biologics vs. Biosimilars
The biologics are large protein molecules that are manufactured through a complex, proprietary process. Because of the size of the molecule and the intricacies for development, it is not possible to make an exact replica of the medication. We can make what are termed biosimilars. These are products that have demonstrated they are highly similar (but not an exact copy) of the original reference product. They have to go through more stringent studies proving no clinically meaningful differences in terms of safety or efficacy compared to the original product. This is a much higher standard and more rigorous process than what generic medications have to go through for approval.
Studies in patients with RA have not demonstrated a significant difference in side effects or disease control when comparing a biologic to a biosimilar.
Patient Assistance Programs
Biologics and biosimilars are expensive, with average wholesale cost estimates ranging in the thousands of dollars per dose. Health insurance will often cover most of this but there can be times when patients do have high out of pocket costs. Each biologic manufacturer offers patient assistance programs which offer many benefits, including financial savings.
Each program offers a variety of benefits which can include:
- A nurse ambassador to answer any medication related questions and to help navigate the insurance approval process and program benefits
- Co-pay assistance to reduce out of pocket costs
- Prescription rebates
- Injection training and safe needle disposal (for injectable biologics)
- Medication reminders
- Symptom tracking
Treatment Goals- How do we Define Remission?
Our goal is to achieve remission or near remission in every patient. We have many standardized assessments that allow us to understand the status of the disease. These include factors like physical exam, laboratory tests, functional assessments and physician and patient overall assessment of disease.
Pharmacologic Treatments and Side Effects
A comprehensive listing of RA treatments and the most common side effects
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
- Methotrexate/Rheumatrex®, Trexall®, Otrexup®, Rasuvo® (oral/Sub Q)
- Side effects: infection, GI upset, blood count abnormalities, liver function abnormalities, mouth sores, fatigue, hair loss, lung problems (rare), fetal toxicity.
- Things to avoid when taking methotrexate: drinking alcohol, pregnancy
- Leflunomide/Arava® (oral)
- Side effects: infection, blood count abnormalities, liver function abnormalities, diarrhea, nausea, fatigue, hair loss, skin rash, fetal toxicity.
- Things to avoid when taking leflunomide: pregnancy
- Hydroxychloroquine/Plaquenil® (oral)
- Side effects: skin rash, low blood sugar, muscle weakness (rare), heart arrhythmias (rare), retinal toxicity
- Sulfasalazine/Azulfidine® (oral)
- Side effects: Blood count abnormalities, nausea, vomiting, diarrhea, skin rashes, reduced sperm count in men (reversible with discontinuation)
Biologics:
- TNF-inhibitors-
- Side effects: Injection site reactions or infusion reactions, infection (especially TB and fungal infections), malignancy (lymphoma, skin cancers), neurologic syndromes (rare), heart failure exacerbations
- Patient assistance:
- Adalimumab/Humira® (Sub Q): HUMIRA® (adalimumab) Cost, Copay, and Savings Card
- Etanercept/Enbrel® (Sub Q): ENBREL Support® | Enbrel® (etanercept)
- Golimumab/Simponi® (IV or SubQ: Talk to Your Doctor | SIMPONI® (golimumab)
- Infliximab/Remicade®: https://www.remicade.com/cost-support.html
- Infliximab/Renflexis®: Patient Education and Support for RENFLEXIS® (infliximab-abda)
- Infliximab/Inflectra®: Reimbursement & Support | Pfizer for Professional (pfizerpro.com)
- Infliximab/Avsola®: HCP Support & Resources | AVSOLA®(infliximab-axxq)
- Certolizumab/Cimzia® (Sub Q): https://www.cimzia.com/cimplicity-program
- IL-6 inhibitors
- Side effects: Injection site reactions or infusion reactions, infection (especially TB, shingles and fungal infections), cholesterol elevation, blood count abnormalities, liver function abnormalities, perforation of the GI tract
- Patient assistance:
- Tocilizumab/Actemra® (IV or Sub Q): ACTEMRA and Rituxan Immunology Co-pay Program (racopay.com)
- Sarilumab/Kevzara® (SubQ): Apply for KevzaraConnect® | KEVZARA® (sarilumab)
- CTLA4-Ig
- Side effects: Injection site reactions or infusion reactions, infection, high blood pressure, nausea, GI upset, blood count abnormalities, COPD flares
Patient assistance:- Abatacept/Orencia® (IV or subQ): Moderate to Severe RA Resources for HCPs | ORENCIA® (abatacept) (orenciahcp.com)
- Anti-CD20 antibodies
- Side effects: Infusion reactions, infection (hepatitis B reactivation), PML (rare), blood count abnormalities
- Patient assistance:
- Rituximab/Rituxan®: ACTEMRA and Rituxan Immunology Co-pay Program (racopay.com)
- Rituximab/Ruxience®: Patient Resources | RUXIENCE® (rituximab-pvvr) | Safety Info
- Rituximab/Truxima®: Support Services – TRUXIMA® (rituximab-abbs) (truximahcp.com)
- Side effects: Injection site reactions or infusion reactions, infection, high blood pressure, nausea, GI upset, blood count abnormalities, COPD flares
Targeted synthetic DMARDs:
- Jak-inhibitors
- Side effects: infection (especially TB, shingles and fungal infections), cholesterol elevation, blood count abnormalities, liver function abnormalities, perforation of the GI tract, blood clots, cardiovascular events (stroke, heart attack) malignancy (lymphoma, skin cancer), increased risk of death
- Patient assistance:
- Tofacitinib/Xeljanz® (oral): Savings And Support | XELJANZ® (tofacitinib) For RA | Safety Info
- Baricitinib/Olumiant® (oral): Savings | Olumiant (baricitinib)
- Upadacitinib/Rinvoq® (oral): RINVOQ® Complete Patient Support and Assistance (rinvoqhcp.com)
Patients should work closely with their rheumatologist to address any medication side effects and to determine which treatment option is right for them.