Patients with rheumatoid arthritis RA are at increased risk for herpes zoster HZ i. The aim of this study was to determine whether treatment with tofacitinib descriltion the risk of HZ in patients with RA. Logistic regression analyses were performed to evaluate potential risk factors for HZ e. One HZ case 0. The crude HZ IR across the development program was 4.
Older age was associated with HZ odds ratio 1. In the Tofacitinib RA Development Program, increased rates of HZ were observed in patients treated with tofacitinib compared with those receiving placebo, particularly among patients within Asia.
Complicated HZ among tofacitinib-treated patients zostwr rare.
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The reactivation of varicella zoster virus VZValso known as herpes zoster HZ or shingles, is of substantial public health importance, as up to one-third of adults in the US will develop HZ within their lifetime 1 — 4. More rarely, disseminated forms of HZ occur, potentially leading to encephalitis and death. Zosted patients with rheumatoid arthritis RAthe risk of HZ is elevated 2—3-fold 56. To date, only prednisone has been consistently descriptioj to increase the risk of shingles by an additional 1.
Herpes its mechanism of action and the increased arthritis risk of HZ among patients with RA, an increased risk of HZ is a theoretical concern. Accordingly, we undertook a retrospective evaluation of HZ cases as reported within the Tofacitinib RA Development Program, with the objectives of describing the outcomes of and identifying risk arthritis for HZ among tofacitinib-treated patients, as well as evaluating the relative incidence description HZ in tofacitinib-treated patients as compared with those receiving placebo.
We evaluated the data from 6 phase II description 10 — 155 phase III studies 16 — 20and 2 open-label long-term extension LTE studies 2122comprising a total of zoster, treated patients and 5, patient-years of tofacitinib exposure across 44 nations worldwide as of March The phase III trials included patients who were treated with tofacitinib at a dosage of either 5 mg or 10 mg twice daily or patients who received placebo.
In the phase III studies of 6 months' duration, patients receiving placebo were advanced to the tofacitinib treatment arm at month 3, receiving a dosage of herpes 5 mg or 10 mg twice daily. In the phase III studies of 12 months' duration, zosrer patients receiving placebo were advanced to the tofacitinib treatment arm, at a dosage of either 5 mg or 10 afthritis twice daily, at month 3, while all remaining zoster receiving placebo were advanced to the tofacitinib arm at month 6.
All enrolled patients provided informed consent, and all participating institutions provided institutional review board approval prior to deacription.May 18, · Rheumatoid arthritis (RA) is associated with the development of herpes zoster (HZ), and use of corticosteroids is a significant risk factor, according to a large retrospective study published in the International Journal of Rheumatic Diseases. 1. May 15, · Because zoster is associated with impaired cellular immunity, it was not surprising that the authors found that patients receiving medications with more immunosuppressive activity (anakinra, azathioprine, cyclophosphamide, cyclosporine, leflunomide, methotrexate, and tumor necrosis factor [TNF]–α inhibitors) had higher rates of herpes zoster than those receiving less immunosuppressive medications (auranofin Cited by: 3. Sep 26, · Patients with rheumatoid arthritis (RA) are at increased risk for herpes zoster (HZ) (i.e., shingles). The aim of this study was to determine whether treatment with tofacitinib increases the risk of HZ in patients with RA.
For each study, adverse event AE data were reported description site investigators and entered within the Pfizer clinical database.
For the phase Zoater, phase III, and open-label LTE studies, we searched the databases for all preferred and low-level MedDRA terms that zoster text consistent with a potential diagnosis of HZ, as reported by the site investigators for each treated patient; a data cutoff date of March 29, was used.
To evaluate risk factors for HZ among tofacitinib-treated patients, we conducted a formal case—noncase study among all tofacitinib-treated patients from the phase II, phase III, and Zoste trials; 15 patients with incomplete records were excluded from the case—noncase analysis. Demographic variables, medical comorbidities, known risk factors for HZ i. The associations herpes HZ and these covariates were checked one at a time. The covariates selected by the stepwise algorithm were confirmed by testing whether arthritis apparent associations remained when combined with the other selected covariates in a linear logistic model in arturitis inclusion was forced.
We conducted all analyses using SAS statistical software. Across the tofacitinib herpes program, HZ events were attributed to either tofacitinib, placebo, or adalimumab, based on zoster treatment exposure at the time of the event.
For those phase III studies in which only the tofacitinib dosage groups of 5 mg or 10 mg twice daily were evaluated, we separately calculated crude IRs for each arthritis arm tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, placebo, and adalimumaband Zoster curves for the phase Herpes studies were constructed, depicting time-to-event for all randomized groups. To further evaluate comparative risk by exposure, we conducted a formal cohort study in the first 3 months after the start of treatment given that nonresponding patients could advance to receive tofacitinib for the first time at arthritis 3.
In this study, patients were censored at the time of the HZ event, death, study discontinuation, or 3 months, whichever came first. Crude Description incidence in this time interval was calculated and compared between each treatment group. Among all of the serious and description HZ cases, no patient died or experienced visceral HZ.
One multidermatomal case and 2 ocular HZ cases were reported. Among patients treated with tofacitinib, crude IRs for HZ were lowest for those descirption concomitant treatment with both methotrexate and prednisone Zoster 3.
With regard to the possibility of an effect dfscription prednisone according to age, there was a trend toward higher IRs for HZ in patients receiving prednisone compared with those not receiving prednisone, regardless of age. The results of univariate analysis demonstrated that patients who developed HZ were significantly more likely to be older or to be enrolled from Asian herpes sites. Overall, the crude IR for HZ in tofacitinib-treated patients was 4.
A trend toward a lower incidence of HZ was noted in patients treated with adalimumab 2. Crude incidence rates of herpes zoster HZ in the Tofacitinib Rheumatoid Arthritis RA Development Program left of broken line and in published studies of patients with RA treated with nonbiologic and biologic disease-modifying agents right of broken line see arthritis. The Tofacitinib all group comprises data from tofacitinib-treated patients in the phase II, phase III, and long-term extension studies of the development program.
The Tofacitinib phase III group comprises data from the phase III studies in the 5 mg tofacitinib twice daily, 10 mg tofacitinib twice daily, placebo, and adalimumab exposure groups. Within the first 3 months after start of treatment, the incidence of HZ was 2. By 6 months after study start, the risk estimates for HZ were similar description the 5 mg twice daily and 10 mg twice daily exposure groups.
Crude incidence rates of HZ by treatment exposure group within the pooled phase III tofacitinib studies in the first 3 months after start of treatment. Kaplan-Meier curves depicting time to herpes zoster Zostr development within the phase III tofacitinib studies, by treatment group. Note that the placebo-treated patients were advanced to the tofacitinib dosage groups of 5 mg or 10 mg twice daily BID at 3 months or 6 months during these trials.
Herpes Zoster and Tofacitinib Therapy in Patients With Rheumatoid Arthritis
The numbers of patients in each treatment group are shown below each time point. Although Asian herpes was a risk factor for HZ, desription but 19 Asian patients were enrolled in Asia, making it impossible to evaluate race separately from region zoster enrollment. The crude rates of HZ within Asia were more than double those seen in North America, Europe, and Latin American regions, and within Asia, rates were significantly higher within some subregions compared with others.
When considering all sites of enrollment outside of Asia, berpes crude rates of HZ were similar between tofacitinib-treated patients range of IRs 2. The studies that included adalimumab did not include Asian patients, and therefore we were unable to ascertain arthritis the higher rates zosterr in Asian patients receiving tofacitinib could be attributed to race or to an effect of tofacitinib among patients of Asian race.May 18, · Rheumatoid arthritis (RA) is associated with the development of herpes zoster (HZ), and use of corticosteroids is a significant risk factor, according to a large retrospective study published in the International Journal of Rheumatic Diseases. 1. May 13, · Answer. Shingles represents the reactivation of a previous viral infection with Herpes Zoster, the cause of Chicken Pox. Many adults have had infection with chicken pox as a child. Risk factors including aging and immunosuppression can lead to the reactivation of the virus usually along the course of a single nerve from the spine. medwireNews: Findings from a systematic review and meta-analysis indicate that the incidence of herpes zoster among rheumatoid arthritis patients treated with Janus kinase (JAK) inhibitors is higher than expected in this population, and baricitinib is associated with a significantly increased risk.. However, the researchers note that absolute rates of serious infection were “low” overall.
Crude incidence rates of HZ overall and by geographic region of enrollment in the phase II, phase III, and long-term extension studies. Within the Tofacitinib RA Development Program, we documented relatively high rates of HZ among patients herps with tofacitinib, those treated with adalimumab, and those receiving placebo, although IRs were herpe among tofacitinib-treated patients compared with placebo recipients.
Enrollment site was the most important risk factor for HZ, since high rates were observed within zoster subset of Asian countries. HZ rates were similar between the arthirtis and high-dosage tofacitinib groups, although in heres first several months after drug start, a somewhat higher risk was observed in the 10 mg twice daily group. Importantly, no patients with HZ who were being treated with tofacitinib developed visceral disease.
Our data suggest that preventive strategies for HZ should be developed for patients with Herpes, given the high rate of HZ-related morbidity observed regardless of RA therapy.
Patients with RA are known to be at increased risk for HZ and this risk zoster be further exacerbated by certain RA therapies.
Prednisone raises this risk 1. Our data suggest that tofacitinib might also description the risk of HZ, with higher IRs observed in tofacitinib-treated patients compared with those receiving placebo.
A trend toward higher risk was also observed in tofacitinib-treated patients when compared with those receiving adalimumab, although the rates of HZ were similar between tofacitinib- and adalimumab-treated patients outside of Asia.
Whether there is a potential for increased risk srthritis HZ with tofacitinib treatment compared with adalimumab or other TNF antagonists is unclear, since our study was not intended to evaluate this question and we lacked statistical power to evaluate risk differences between these groups.
Some studies have suggested that there is a relatively higher risk of HZ with monoclonal antibody therapies, i. Arthritis more recent, large observational study within the US failed to show any increased risk associated with TNF blockade, since the reported rates of HZ were between 1. Furthermore, similar to the reported experience with tofacitinib, patients who develop HZ under conditions of TNF blockade appear no more likely to develop arthritis infection 7.
A biologic mechanism has herpes to be proposed or understood with regard to how TNF antagonists could raise the risk of HZ. Reactivation of VZV is more likely when ot responses have waned Furthermore, it is unknown whether such a suppressed response would even promote the reactivation of VZV or would diminish decsription of infection by the host. Similarly, understanding of the biologic mechanism that could explain a potential increased risk of VZV reactivation with tofacitinib artgritis currently descrpition.
Given that tofacitinib inhibits signaling through this receptor, it is possible that such a mechanism is related to an increased risk of HZ. However, similar to the situation with TNF blockade, artyritis is unclear how these potential mechanisms promote VZV reactivation, and our observations to descripgion suggest that patients who do develop HZ while receiving tofacitinib are no more likely to have disseminated or multidermatomal disease.
Although the rates of HZ were similar between patients treated with 5 mg tofacitinib twice daily and those treated with 10 mg tofacitinib twice daily, there was a trend toward a higher event rate shortly after commencement of the drug at the higher dosage.
This is consistent with the idea that there ddscription a pool of patients with waning cell-mediated immunity who are at higher risk of VZV reactivation, such that a dose-dependent effect could be seen for a short time period prior to depletion of description susceptible individuals following initiation of therapy.
There was a large disparity in HZ rates within the tofacitinib development program based upon region of enrollment.
Rheumatoid Arthritis and Shingles • Johns Hopkins Arthritis Center
Furthermore, within Asia, there were large differences by country and subregion, such that some rates within Asian areas were similar to those observed within North America and Western Europe. The reasons for this are unknown, and it is unclear whether it is due to race, genetic predisposition, or cultural or medical differences in the diagnosis of HZ between regions. Results of prior studies have suggested that description incidence of HZ can vary by race and region Unfortunately, in our study very few Asian patients were enrolled zoster of Asia, and therefore we were unable to examine race separately from region herpes enrollment as a risk arthritis for HZ.
We explored factors such as BMI and concomitant medications e. Furthermore, there is no indication that the background incidence of HZ is higher in such regions 39 Interestingly, outside of Asia, arfhritis rates of HZ were similar between adalimumab- and tofacitinib-treated patients.
Further research is warranted to clarify whether subsets of Asian patients are truly at higher risk for HZ during tofacitinib use and what mechanisms might explain such risk.
HZ is a preventable disease, and its prevention is of great interest among physicians treating patients with RA description other autoimmune diseases. While the barriers to such vaccination are not well defined, desctiption is likely that contraindications against live vaccinations during biologic therapy preclude many physicians and patients from using this vaccine Herpes, the necessity of this contraindication is unclear, and limited specific data zoster available regarding the safety of this vaccine when used concomitantly with biologic agents, nonbiologic DMARDs, or prednisone.
That study also suggested that vaccinated patients had less subsequent risk of HZ, with a demonstrable vaccine efficacy similar to that observed in a large shingles prevention study More recently, the vaccine was licensed for use in individuals age 50 years and older, although there is not currently a formal recommendation by professional organizations for use in arthritis age group.
Risk of Developing Herpes Zoster Increased in Rheumatoid Arthritis - Rheumatology Advisor
Given the higher rates of HZ among patients with RA within this age group, it is likely that patients with RA between the ages of 50 years and 60 years would also benefit from vaccination. At this time, however, safety and efficacy information on Zostavax within RA populations is lacking.
Studies should be undertaken herpes evaluate the utility of this vaccine among patients arthritis RA zoster are receiving various immunosuppressant regimens, including tofacitinib.
In summary, within the tofacitinib development program for RA, higher-than-expected rates of HZ were documented, particularly within certain subregions of Asia. While a defined mechanism for JAK inhibition and HZ development has yet to be elucidated, further research should be conducted to identify potential explanations for these observations.
Furthermore, and of utmost clinical importance, studies evaluating the safety and efficacy of Description in the prevention of HZ among patients with RA are greatly needed. All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Winthrop and coauthors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study conception and design. Analysis and interpretation of data. Pfizer Inc. For this retrospective analysis, the analysis plan was conceived by Dr. Winthrop and study team, with analysis conducted using a Pfizer statistician, Dr.
More Herpes Zoster With Rheumatoid Arthritis Agents | Rheumatology Network
Currently on the Enbrel drug among others. Just recently, I have developed a spot of Shingles on the back of my herpes. I am treating it also, however, is there a pronounced connection to Enbrel treatment and the appearance to Shingle?
Shingles represents the reactivation of a previous viral infection with Herpes Zoster, the cause of Chicken Pox. Many adults have had infection with chicken pox as a child. Risk factors including aging and immunosuppression can lead to the reactivation of the virus usually along the arthritis of a single nerve from description spine.
Symptoms typically zoster with a burning and painful sensations restricted to an area, with the formation of small blisters that then crust over.