Herpes Reactivation Observed With TNF Inhibitors

BARCELONA — The risk of reactivation of herpesvirus infection is increased among patients with rheumatoid arthritis who are treated with the anti-tumor necrosis factor agents, and especially with the monoclonal antibodies infliximab and adalimumab, Dr. Anja Strangfeld said at the annual European Congress of Rheumatology.

“An increased risk of bacterial infections during treatment with the TNF-blocking drugs is well documented, but less attention has been paid to viral infection and reactivation in this regard, so we analyzed data from the German biologics register to ascertain the incidence and risk factors for reactivation of herpesvirus infection,” said Dr. Strangfeld, who is an epidemiologist with the German Rheumatism Research Center, Berlin.

Among the patients enrolled in the registry as of June 2006, 1,132 had received etanercept, 563 infliximab, and 1,155 adalimumab.

Among these patients, 160 cases of herpes in 144 patients were reported, with 84 cases being herpes zoster and 76 being herpes simplex, she said.

Of note, 15 of the cases of herpes zoster were serious, with 13 being the rare multidermatomal form. An additional two were serious ophthalmic herpes; this results when the virus, which remains latent and lifelong in the sensory ganglia, reactivates in the geniculate ganglion.

The incidence of zoster reactivation among patients being treated with infliximab, adalimumab, and etanercept was compared with rates among control RA patients receiving conventional disease-modifying antirheumatic drugs, and was found to be higher rates among the biologic-treated patients overall. (See box.)

“We also analyzed the rates for the TNF blockers according to their molecular type, because previous analyses of rates of tuberculosis reactivation found differences in rates among patients receiving the monoclonal antibodies infliximab and adalimumab, compared with those receiving the receptor fusion protein etanercept,” she said.

Higher rates were seen for the monoclonal antibodies than for etanercept, and particularly for the serious multidermatomal and ophthalmic infections, she noted.

Analysis of risk factors for reactivation identified higher risk for increasing age (hazard ratio 1.24) and for increased duration of disease (HR 1.10).

Drug exposure also influenced risk. Prednisone in daily doses of 10 mg or more was associated with a higher risk (HR 3.53) than were doses less than 5 mg (HR 2.4).

On multivariate analysis, exposure to any TNF blocker was associated with a higher risk (HR 1.77), compared with patients in the control group. A significantly higher twofold risk was seen for infliximab and adalimumab (HR 1.96) but not for etanercept (HR 1.51).

“We therefore concluded that prednisone and anti-TNF use increased the risk for herpes reactivation, and that the risk is higher with treatment with the monoclonal antibodies, which may be due to a different mode of action,” she said.

The study was supported by a joint unconditional grant from Wyeth Pharma GmbH, Essex Pharma GmbH, Amgen GmbH, and Abbott GmbH.

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BARCELONA — The risk of reactivation of herpesvirus infection is increased among patients with rheumatoid arthritis who are treated with the anti-tumor necrosis factor agents, and especially with the monoclonal antibodies infliximab and adalimumab, Dr. Anja Strangfeld said at the annual European Congress of Rheumatology.

“An increased risk of bacterial infections during treatment with the TNF-blocking drugs is well documented, but less attention has been paid to viral infection and reactivation in this regard, so we analyzed data from the German biologics register to ascertain the incidence and risk factors for reactivation of herpesvirus infection,” said Dr. Strangfeld, who is an epidemiologist with the German Rheumatism Research Center, Berlin.

Among the patients enrolled in the registry as of June 2006, 1,132 had received etanercept, 563 infliximab, and 1,155 adalimumab.

Among these patients, 160 cases of herpes in 144 patients were reported, with 84 cases being herpes zoster and 76 being herpes simplex, she said.

Of note, 15 of the cases of herpes zoster were serious, with 13 being the rare multidermatomal form. An additional two were serious ophthalmic herpes; this results when the virus, which remains latent and lifelong in the sensory ganglia, reactivates in the geniculate ganglion.

The incidence of zoster reactivation among patients being treated with infliximab, adalimumab, and etanercept was compared with rates among control RA patients receiving conventional disease-modifying antirheumatic drugs, and was found to be higher rates among the biologic-treated patients overall. (See box.)

“We also analyzed the rates for the TNF blockers according to their molecular type, because previous analyses of rates of tuberculosis reactivation found differences in rates among patients receiving the monoclonal antibodies infliximab and adalimumab, compared with those receiving the receptor fusion protein etanercept,” she said.

Higher rates were seen for the monoclonal antibodies than for etanercept, and particularly for the serious multidermatomal and ophthalmic infections, she noted.

Analysis of risk factors for reactivation identified higher risk for increasing age (hazard ratio 1.24) and for increased duration of disease (HR 1.10).

Drug exposure also influenced risk. Prednisone in daily doses of 10 mg or more was associated with a higher risk (HR 3.53) than were doses less than 5 mg (HR 2.4).

On multivariate analysis, exposure to any TNF blocker was associated with a higher risk (HR 1.77), compared with patients in the control group. A significantly higher twofold risk was seen for infliximab and adalimumab (HR 1.96) but not for etanercept (HR 1.51).

“We therefore concluded that prednisone and anti-TNF use increased the risk for herpes reactivation, and that the risk is higher with treatment with the monoclonal antibodies, which may be due to a different mode of action,” she said.

The study was supported by a joint unconditional grant from Wyeth Pharma GmbH, Essex Pharma GmbH, Amgen GmbH, and Abbott GmbH.

ELSEVIER GLOBAL MEDICAL NEWS

BARCELONA — The risk of reactivation of herpesvirus infection is increased among patients with rheumatoid arthritis who are treated with the anti-tumor necrosis factor agents, and especially with the monoclonal antibodies infliximab and adalimumab, Dr. Anja Strangfeld said at the annual European Congress of Rheumatology.

“An increased risk of bacterial infections during treatment with the TNF-blocking drugs is well documented, but less attention has been paid to viral infection and reactivation in this regard, so we analyzed data from the German biologics register to ascertain the incidence and risk factors for reactivation of herpesvirus infection,” said Dr. Strangfeld, who is an epidemiologist with the German Rheumatism Research Center, Berlin.

Among the patients enrolled in the registry as of June 2006, 1,132 had received etanercept, 563 infliximab, and 1,155 adalimumab.

Among these patients, 160 cases of herpes in 144 patients were reported, with 84 cases being herpes zoster and 76 being herpes simplex, she said.

Of note, 15 of the cases of herpes zoster were serious, with 13 being the rare multidermatomal form. An additional two were serious ophthalmic herpes; this results when the virus, which remains latent and lifelong in the sensory ganglia, reactivates in the geniculate ganglion.

The incidence of zoster reactivation among patients being treated with infliximab, adalimumab, and etanercept was compared with rates among control RA patients receiving conventional disease-modifying antirheumatic drugs, and was found to be higher rates among the biologic-treated patients overall. (See box.)

“We also analyzed the rates for the TNF blockers according to their molecular type, because previous analyses of rates of tuberculosis reactivation found differences in rates among patients receiving the monoclonal antibodies infliximab and adalimumab, compared with those receiving the receptor fusion protein etanercept,” she said.

Higher rates were seen for the monoclonal antibodies than for etanercept, and particularly for the serious multidermatomal and ophthalmic infections, she noted.

Analysis of risk factors for reactivation identified higher risk for increasing age (hazard ratio 1.24) and for increased duration of disease (HR 1.10).

Drug exposure also influenced risk. Prednisone in daily doses of 10 mg or more was associated with a higher risk (HR 3.53) than were doses less than 5 mg (HR 2.4).

On multivariate analysis, exposure to any TNF blocker was associated with a higher risk (HR 1.77), compared with patients in the control group. A significantly higher twofold risk was seen for infliximab and adalimumab (HR 1.96) but not for etanercept (HR 1.51).

“We therefore concluded that prednisone and anti-TNF use increased the risk for herpes reactivation, and that the risk is higher with treatment with the monoclonal antibodies, which may be due to a different mode of action,” she said.

The study was supported by a joint unconditional grant from Wyeth Pharma GmbH, Essex Pharma GmbH, Amgen GmbH, and Abbott GmbH.

ELSEVIER GLOBAL MEDICAL NEWS