DMARDs, Biologics for RA, and Needle-Free Injections

Patient Expert

Finding an effective medication and sticking with it are very important when you live with a serious disease such as rheumatoid arthritis.   RA doesn't damage only your joints, it can attack your lungs, heart, eyes, and the tissue surrounding your joints.   Disease-modifying anti-rheumatic drugs (DMARDs) are commonly used to treat RA by slowing down the disease.

Traditional DMARDs which have been used for decades to treat RA include methotrexate, (Plaquenil) hydroxychloroquine, Azulfidine (sulfasalazine), and Arava (leflunomide). Each of these medications is available as an oral pill, taken either daily or weekly.   Methotrexate is available both as a pill and as an injection.

Biologics, a more recent class of DMARDs, are genetically engineered medications which copy the effects of substances naturally made by the body's immune system to help block inflammation.   These drugs can target specific immune system abnormalities which lead to joint inflammation and other problems caused by RA.   Biologic drugs are very expensive due to their complex manufacturing process.

Biologic drugs have been used to treat RA during the past ten years. and are typically used as second-line drugs for patients who do not respond to traditional DMARDs.   Some biologics are used as first-line drugs for select patients with moderately to severely active RA.   There are nine biologics which are used for the treatment of RA, with the first receiving FDA approval in 2001.   A tenth biologic drug, Xeljanz (tofacitinib), was approved in November 2012 and should hit the market soon.

Traditionally, RA patients may be prescribed treatment with one or more of the non-biologic DMARDs before receiving treatment with a biologic drug (which is considered more aggressive).   A recent meta-analysis of 70 studies involving drugs used for RA compared the effectiveness of various treatments and combination of treatments in preventing joint erosion caused by RA as seen on x-ray image.   One outcome of the analysis revealed that combination treatment with 2 DMARDs plus periodic steroid treatment may be as effective as a biologic agent plus methotrexate (Graudal, 2010).

Besides being very expensive, a drawback to the biologic medications has been that they are given as subcutaneous injection (shot under the skin) or intravenous (IV) infusion.   However, many patients who fear self-injections are able to learn to give themselves shots with appropriate training and support.

Xeljanz (tofacitinib), the drug FDA approved in November for patients with moderately to severely active RA who didn't respond to or could not tolerate methotrexate, is an oral medication (oral tablet) taken twice daily.

A recent survey of over 300 rheumatoid arthritis patients sought to understand the factors that influence a patient's preference regarding self-injectable drug therapies, i.e. choosing to start treatment and stick with it.   One goal of the study was to explore how the availability of both standard needle/syringe therapies and novel needle-free alternatives impact a patient's willingness to use injectable therapy.

Preliminary findings from the survey were announced in November 2012.   In the survey, nearly half (45%) of RA patients reported being needle-phobic (8% extremely, 14% very, 23% somewhat).   Only 53% were likely to accept a prescription for a self-injected therapy.   If a needle-free option were offered, the number of patients willing to use a self-injected medication increased to 70% which represents a 30% increase in the acceptance rate of self-injected medication.   More than 20% would not consider using a medication that required self-injection.

One of the sponsors of the survey, Zolgenix, Inc., is a pharmaceutical company that has co-developed a novel needle-free alternative to traditional needle and syringe self-injections.   The DosePro ® drug delivery system is designed to give subcutaneous injection with pre-filled, single-dose syringes without a needle. With the DosePro ® system, compressed nitrogen gas when released propels a plunger forward in the syringe very quickly and under pressure such that the liquid pierces the skin and a full dose of medication is delivered under the skin (subcutaneously) in about 1/10th of a second.

Traditional DMARDs:
Methotrexate - Oral tablet, or Subcutaneous injection, or Intramuscular injection
Plaquenil (hydroxychloroquine) - Oral tablet
Azulfidine (sulfasalazine) - Oral tablet, approved in Oct 1996
Arava (leflunomide) - Oral tablet, approved in Sept 1998

Biologic DMARDs:
Remicade (infliximab) - IV infusion, approved in Jan 2001
Kineret (anakinra) - Subcutaneous injection, approved Nov 2001
Enbrel (etanercept) - Subcutaneous injection, approved in Jan 2002
Humira (adalimumab) - Subcutaneous injection, approved in Dec 2002
Orencia (abatacept) - IV infusion or Subcutaneous injection, approved Dec 2005
Rituxan (rituxumab) - IV infusion, approved Feb 2006
Simponi (golimumab) - Subcutaneous injection, approved Apr 2009
Cimzia (certolizumab) - Subcutaneous injection, approved May 2009
Actemra (tocilizumab) - IV infusion, approved Jan 2010
**Xeljanz (tofacitinib) - Oral tablet, approved in Nov 2012

Questions: Does it matter to you how medications are delivered (oral, injection, IV) if they are equally effective with similar side-effects?   Are you afraid of needles?   Would a needle-free option be something you are interested in?   How many DMARDs have you tried and what was your experience?

Report serious adverse events you may have experienced from medical products, including medication, through the FDA MedWatch online reporting system.


Cush JJ. Biologic Treatments for Rheumatoid Arthritis.   American College of Rheumatology website.   Accessed December 1, 2012.

Graudal N, Jürgens G. Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: Meta-analysis of 70 randomized placebo-controlled or drug-controlled studies, including 112 comparisons. Arthritis & Rheumatism 2010;62:2852-2863. doi:  10.1002/art.27592

Preliminary Findings From Rheumatoid Arthritis Patient Survey Reveal Strong Interest in Needle-Free Self-Injection.   Press release by Zolgenix, Inc. November 13, 2012.