Common rheumatoid arthritis (RA) drugs methotrexate and biologics, but not prednisolone, may increase the risk for herpes zoster, according to a study presented at the European League Against Rheumatism (EULAR) Congress 2017, held June 14-17 in Madrid, Spain.1 These results highlight a shift in RA’s treatment paradigm, in which biologics are increasingly being prescribed. Indeed, a 2006 study implicates prednisone, cyclophosphamide, azathioprine, and leflunomide, as well as COX-2 nonsteroidal anti-inflammatory drugs but not methotrexate or biologics, as risk factors for herpes zoster.2
The same study reported an incidence of 13.2 per 1000 patient-years (95% CI, 11.9-14.5) of herpes zoster among individuals with RA, and a 2015 analysis by the group from the current study found that incidence to be 9.1 per 1000 patient-years (95% CI, 6.2-12.9).2,3 The latter study, which was conducted on the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) Japanese cohort, found that 3% of the patients enrolled between 2005 and 2010 had their RA treated with biologics at baseline.
The use of biologics for RA management has dramatically increased in recent years, with a rise from an estimated 2.8% in 2000-2001 to 18.9% in 2008-2009.4 The researchers sought to evaluate the impact of new prescribing trends, with the introduction of new disease-modifying antirheumatic drugs and the increasing use of biologics, on the incidence of herpes zoster, as its risk had previously been associated with drug use in patients with RA.
They leveraged data from the IORRA cohort of patients with RA who consulted the Institute of Rheumatology at Tokyo’s Women’s Medical University in Japan from 2010 to 2015. A total of 7815 records were analyzed (84.7% women; median age, 61.0 years [interquartile range, 49.7-68.9]; 10 years disease duration [interquartile range, 4-18 years]), corresponding to 25,863 observed patient-years. Patients were treated a baseline with the following drugs: 36.8% with a median prednisolone dose of 4 mg/day (interquartile range, 2-5 mg/day), 70.4% with a median methotrexate dose of 8 mg/week (interquartile range, 6-10), and 14.7% with biologics.
A total of 309 patients reported being infected with herpes zoster, verified with medical records, with a total of 340 events and 21 patients displaying multiple events. The standardized incidence rate of herpes zoster for the whole cohort was 8.5 per 1000 patient-years (95% CI, 6.9-10.5), with a sex distribution of 6.0 in men (95% CI, 3.7-9.2) and 11.0 in women (95% CI, 8.7-13.7).
Hazard ratios (HRs) were as follows:
Unit increase of age: 1.14 (95% CI, 1.03-1.26; P <.05)
Japanese version of the Stanford Health Assessment Questionnaire score 0.5-1.5 (with 0 as a reference score): 1.51 (95% CI, 1.09-2.10; P <.05)
Methotrexate use: 1.58 (95% CI, 1.06-2.36; P <.05)
Biologics use: 1.88 (95% CI, 1.44-2.47; P <.01)
Prednisolone was not found to constitute a risk factor (for doses <5 mg/day: HR, 1.17 [95% CI, 0.91-1.51; P =.22]; for doses ≥5 mg/day: HR, 1.17 [95% CI, 0.72-1.91; P =.52]).
According to the researchers, this shift in the identity of RA drugs that represent a risk factor for herpes zoster (ie, methotrexate and biologics vs prednisolone) is a sign of an “era when the use of biologic [has become] frequent.”
A number of study authors report receiving consulting fees from pharmaceutical companies, including Bristol-Myers, Novartis, and Pfizer.
1. Yamaguchi R, Nakajima A, Inoue E, et al. Risk of herpes zoster in patients with rheumatoid arthritis in the biologics era based on the IORRA cohort. Presented at: European League Against Rheumatism (EULAR) Congress 2017; June 14-17, 2017; Madrid, Spain. doi: 10.1136/annrheumdis-2017-eular.3046.
2. Wolfe F, Michaud K, Chakravarty EF. Rates and predictors of herpes zoster in patients with rheumatoid arthritis and non-inflammatory musculoskeletal disorders. Rheumatology (Oxford). 2006;45(11):1370-1375. doi: 10.1093/rheumatology/kel328
3. Nakajima A, Urano W, Inoue E, Taniguchi A, Momohara S, Yamanaka H. Incidence of herpes zoster in Japanese patients with rheumatoid arthritis from 2005 to 2010. Mod Rheumatol. 2015;25(4):558-561. doi: 10.3109/14397595.2014.984829
4. Ng B, Petersen N, Yu H-J, et al. 10-Year Trends in the Use of Disease Modifying Anti-Rheumatic Drugs (DMARDs) and Biologic Agents in Rheumatoid Arthritis: A National Veteran Affairs Study. Presented at: American College of Rheumatology (ACR) 2012 Annual Meeting; November 9-14, 2012; Washington, DC.