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Healing Choices for RA, Issue #013 -- Does smoking affect your chances of responding to therapy?
November 22, 2012

Does smoking affect your chances of responding to therapy?

Here in the US, we wish you a wonderful Happy Thanksgiving, a celebration and a time of gratitude for the fall harvest. No matter where you are, let’s be thankful for fresh air and …..

While some may smoke or live with friends and family who smoke, let’s be grateful that we have an option to choose what we put into our bodies.

Smoking is considered a risk factor for getting rheumatoid arthritis. I recently summarized the effects of smoking on bone health, joint issues, immune responses, and response to therapy for RA patients. This review is published online in Journal of Clinical and Cellular Immunology (1) in the “articles in press” section.

Smoking is a personal type of environmental pollution.

Smoking releases more than 4000 compounds. Smoke harms the health of bones and joints as well as the cardiovascular and respiratory systems. Second-hand smoke may have similar effects.

Smokers have a higher risk for bone fractures, osteoporosis, bone loss, and degeneration of intervertebral discs. Bone fractures in most smokers heal slower than broken bones in healthy non-smokers.

Smoke and citrullination of proteins

Smoke causes some proteins in the lungs to become citrullinated. Whether smoking induces citrullination of some proteins in the joints has not been reported.

However, some RA patients develop antibodies to citrullinated proteins found in the joints. Antibodies to citrullinated proteins in RA patients are measured by the CCP test.

RA patients who generated antibodies to cyclic citrullinated proteins (CCP) have a higher risk for joint damage.

Smoking lowers responses of recently-diagnosed RA patients

Recently-diagnosed RA patients have higher response rates to most medications than RA patients with long-standing disease. Physicians refer to treatment of recently-diagnosed RA patients as a “window of opportunity”.

However, recently-diagnosed RA patients who smoke have lower response rates than recently-diagnosed nonsmokers.

In contrast to non-smokers, the response rates of recently-diagnosed RA smokers are similar to long-term RA patients.

Smoking increases serum levels of TNF

Smoking increases serum levels of TNF alpha but not TNF production from isolated dendritic cells. Many RA patients (15-65%) benefit from treatment with one of the biologic therapies that inhibit TNF alpha. Three anti-TNF inhibitors have been used for years: infliximab (Remicade), etanercept (Enbrel) or adalimumab (Humira).

Smoking reduces responses to one of the three anti-TNF inhibitors

Several studies suggest that smokers with RA have lower response rates to TNF blockers. Additional studies indicate that RA patients who smoked had significantly lower response rates to infliximab (Remicade) (2, 3). In contrast, both smokers and nonsmoking RA patients responded to treatment with two other anti-TNF agents, etanercept (Enbrel) or adalimumab (Humira) at similar rates (2, 3). If interested, see the JCCI paper for more details and for references. This paper is an open access article so you can make as many copies as you’d like.

Choices to Consider

Thus, if you’re an RA patient who smokes, first consider giving up or at least reducing your smoking.

In the meantime, if your physician suggests that you consider taking a TNFalpha inhibitor and you decide that it’s the best course of action, then discuss the possibility of trying etanercept (Enbrel) or adalimumab (Humira) before infliximab (Remicade).

As a smoker, your chances of responding to etanercept (Enbrel) or adalimumab (Humira) are similar to those of nonsmokers.

Other Lifestyle Choices

You may also want to consider lifestyle choices that reduce your inflammation.

Mild exercise helps reduce levels of inflammatory cytokines. Adequate vitamin D (800U or more) helps reduce inflammation. Best source is still Sunlight for 20 min a day.

Omega-3 oils in freshly ground flaxseed, walnuts, and cold water fish help reduce inflammation: after modification, they act as an “off” signal for inflammation. Omega 6 oils and transfats (any hydrogenated vegetable or animal oil) increase your level of inflammation. The omega 6 oils — corn, safflower, sunflower— provide the building blocks for some molecules that increase inflammation. Wishing you a wonderful day of thanks, no matter where you are. Here’s to your healing!

Have a great weekend!



Kathy Molnar-Kimber, Ph.D.

P.S. I recently gave a slide presentation on Nutritional deficiencies as a risk factor for rheumatoid arthritis in Montreal at a conference on Traditional Chinese Medicine. Very interesting presentations but I’ll write about them another time.

P.P.S. Consultations for a second opinion on your specific case of RA are available. Potential causes and lifestyle suggestions that have helped me reduce and eliminate disruptions from RA symptoms can be discussed. Disclaimer: This information is solely information and not intended to diagnose, treat, mitigate or cure any disease. Discuss any suggestions with your healthcare provider to determine their suitability for your case of RA. Please see the disclaimer.


1. Molnar-Kimber KL. 2012. Effects of Smoking on Immunologic and Skeletal Mechanisms Involved in Rheumatoid Arthritis and Responses of Various Biologic Therapies for Ra J. Clin. Cell. Immunol. S6: in press.

2. Hyrich KL, Watson KD, Silman AJ and Symmons DP. 2006. Predictors of Response to Anti-Tnf-Alpha Therapy among Patients with Rheumatoid Arthritis: Results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford). 45: 1558-1565.

3. Soderlin MK, Petersson IF, Bergman S and Svensson B. 2011. Smoking at Onset of Rheumatoid Arthritis (Ra) and Its Effect on Disease Activity and Functional Status: Experiences from Barfot, a Long-Term Observational Study on Early Ra. Scand. J. Rheumatol., 40: 249-255.

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