Rheumatoid Arthritis Patients Receiving Anti-TNF Therapy Can Be Effectively Immunized

Newswise — Despite being immunosuppressed, patients with rheumatoid arthritis are able to develop protective antibodies following pneumococcal and influenza vaccinations when also treated with anti-TNF agents, thus reducing their risk for developing the flu and the most common type of bacterial pneumonia, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Washington, DC.

Flu shots are given annually to combat the influenza that plagues 5 to 20 percent of Americans each year. In many cases, these infections can lead to severe complications, especially in the elderly and patients with chronic illnesses, causing approximately 36,000 annual deaths among Americans. Because patients with rheumatoid arthritis are immunosuppressed, there is longstanding concern about the effectiveness of vaccinations for disease prevention.

To examine the effectiveness of anti-bacterial pneumococcal vaccination and anti-viral influenza vaccinations, 226 patients with active rheumatoid arthritis participated in a double-blind study during the 2003-2004 influenza season. Each patient received either the biologic, adalimumab, or a placebo over a 30-day period. Those taking the biologic drug were given 80 mg on day 1 followed by 40 mg on days 15 and 29. Vaccines for pneumococcus (23-valent) and influenza virus (trivalent subvirion) were administrated intramuscularly to all patients on day 8. Response to vaccination was determined 4 weeks following vaccination (day 36).

Researchers found no significant difference between the adalimumab and placebo groups among the 208 patients with analyzable data when comparing the percentages of patients with protective antibody concentrations in response to both vaccines. This indicates that adalimumab therapy did not diminish the participants' abilities to develop the necessary protective immune response. Preliminary studies of several other biologic agents in rheumatoid arthritis suggest similar results, but this is the largest placebo-controlled study conducted to date.

"As physicians, we believe all patients at risk of influenza or pneumococcal pneumonia should receive vaccination regardless of whether or not they have rheumatoid arthritis," says Jeffrey Kaine, MD, Director, Sarasota Arthritis Research Center, Sarasota, Florida, and an investigator in the study. "However, the fact that we now have evidence to suggest that these vaccines are effective in the rheumatoid arthritis patient population offers physicians and their patients peace of mind."

The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see http://www.rheumatology.org/annual.

Presentation Number: 1235

Abilities to Develop Protective Antibodies to Pneumococcal and Influenza Vaccine are Maintained in Rheumatoid Arthritis (RA) Patients Treated with Adalimumab (Humira®)

J. Kaine1, A. Kivitz2, C. Birbara3, A. Y. Luo4. 1Sarasota Arthritis Center, Sarasota, FL; 2Altoona Center for Clinical Research, Duncansville, PA; 3Clinical Pharmacology Study Group, Worcester, MA; 4Abbott, Parsippany, NJ

Purpose: Streptococcus pneumoniae and influenza virus are prominent infectious agents that can cause morbidity and mortality in RA. Although routine pneumococcal and influenza vaccinations are recommended, treatment with steroids, immunosuppressants, and/or TNF antagonists may affect immune response. This study evaluated the effects of adalimumab on antibody (Ab) response to pneumococcal (pneum) and influenza (infz) vaccines in adult RA pts.Methods: Patients (pts) with active RA were enrolled during the 2003-04 US infz season into this double-blind, placebo-controlled study. Pts randomized to adalimumab received 80 mg on Day 1 followed by 40 mg on Days 15 and 29. Standard 23-valent pneum and trivalent subviron infz virus vaccines were administered intramuscularly to all pts on Day 8. Ab titers (9V, 14, 18C, 19F, and 23F for pneum; H1N1, H3N2, and Hong Kong for infz) were measured on Day 8 (prevaccination) and Day 36. Protective Ab status for pneum vaccine was defined as ≥1.6 mg/mL in ≥3 of 5 antigens and response to vaccination was defined as ≥2-fold increase from baseline (BL) in Ab titer in ≥3 of 5 antigens. Protective Ab status for infz vaccine was defined as ≥1:40 titer in ≥2 of 3 antigens, and response to vaccination was defined as ≥4-fold increase from BL in Ab titer in ≥2 of 3 antigens.Results: A total of 226 pts were randomized. The analysis comprised data from 208 pts who had received at least the first 2 doses of blinded study drug (on Days 1 and 15) and had both pre- and post-vaccine Ab analyses. No significant difference between groups existed in either BL demographics or Ab levels.For pneum vaccine, the %s of pts with protective Ab status 4-weeks after vaccination were comparable in both arms, as were the %s of pts in both groups who developed Ab response. For infz vaccine, the %s of pts who had protective Ab status 4-weeks after vaccination were also comparable in the 2 groups. The % of pts who developed infz Ab response was smaller in the adalimumab arm, driven by the subgroup of pts that already had protective Ab status at BL. Among pts without protective Ab status at baseline, the response rates were similar in the 2 groups. The frequencies and types of adverse events were similar to those observed in other adalimumab studies.

4 Weeks After Vaccination Placebo AdalimumabInfluenza: protective antibody status 103/109 (94.5%) 97/99 (98.0%)Influenza: developed antibody response 69/109 (63.3%) 51/99 (51.5%)Response in patients with protective influenza antibody status at baseline 35/63 (55.6%) 21/58 (36.2%)

Response in patients without protective influenza antibody status at baseline 34/46 (73.9%) 30/41 (73.3%)

Pneumococcal: protective antibody Status 89/109 (81.7%) 85/99 (85.9%)Pneumococcal: developed antibody response 44/109 (40.4%) 37/99 (37.4%)Response in patients with protective pneumococcal antibody status at baseline 17/62 (27.4%) 16/57 (28.1%)

Response in patients without protective pneumococcal antibody status at baseline 27/47 (54.7%) 21//42 (50.0%)

Conclusion: Adalimumab does not diminish ability to develop protective antibody from pneumococcal and influenza vaccines in RA pts. These findings demonstrate that RA pts on adalimumab can be effectively and safely immunized with these vaccines.

Disclosure Block: J. Kaine, Abbott, 5 Consulting fees.