Comparative risk of herpes zoster in patients with psoriatic disease on systemic treatments: a systematic review and network meta-analysis

Abstract

Background: Numerous previous studies have examined risk of herpes zoster (HZ) in psoriatic disease; however, the results of these studies are conflicting and the relative risks associated with different treatments remain largely unknown. In this meta-analysis, we examined the relative risk of HZ associated with systemic treatments for psoriatic disease. Methods: PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched to identify relevant English-language studies published up to April 2021. Data were extracted using a standardized data extraction form. Network meta-analyses (NMA) was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We examined the differences in HZ risk (incidence rate ratio; IRR) between treatments using a random-effects model for direct pairwise comparisons and NMA. The surface under the cumulative ranking area was calculated to rank the HZ risk for each treatment condition. Results: This study analyzed 13 studies including 19 treatment arms involving a total of 443,104 patients with psoriatic disease. Corticosteroids (CS) [IRR, 2.56; 95% confidence interval (CI), 1.59–4.13], a Janus kinase inhibitor (JAKi; tofacitinib) (IRR, 2.34; 95% CI, 1.03–5.32), infliximab (IRR, 2.32; 95% CI, 1.27–4.21), conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) + CS (IRR, 2.26; 95% CI, 1.23–4.17), anti-tumor necrosis factor-α (anti-TNF-α) + csDMARDs and/or CS (IRR, 2.13; 95% CI, 1.38–3.31), csDMARDs (IRR, 1.62; 95% CI, 1.18–2.22), and anti-TNF-α except infliximab (IRR, 1.61; 95% CI, 1.13–2.30) were all associated with a significantly higher HZ risk compared to controls. CS treatment possessed the highest HZ risk, followed by infliximab and JAKi (tofacitinib). Phosphodiesterase-4 inhibitor, anti-interleukin-17, -23 or -12/23, phototherapy, and acitretin showed a risk similar to controls without significant differences. Conclusion: The NMA demonstrated CS, infliximab, and JAKi (tofacitinib), and several combination treatments were associated with higher HZ risk in patients with psoriasis and psoriatic arthritis. Differences in HZ risk should be taken into consideration when considering optimal psoriasis treatment.

The Risk of Herpes Zoster Events in Patients with Spondyloarthritis and the Effect of BNT162b2 mRNA COVID-19 Vaccine

“…Second, some DMARDs which are known to be associated with HZ reactivation, such as rituximab, mycophenolate mofetil (MMF), and GC [ 36 , 50 ], are not utilized in the treatment arsenal of SpA and therefore were not included in our study. However, Jak-I, which is used in the treatment regimen of PsA and known to be associated with HZ risk [ 11 , 12 , 52 ], was represented in our study and indeed found to be associated with an increased risk of HZ reactivation.…”

“…For instance, in the case of AS, a study by Wong et al showed no increase in the incidence of HZ in AS relative to RA (stratified HR = 0.97; 0.58–1.61) [ 9 ], while a Taiwanese study by Wang et al showed no difference in the incidence rate of HZ between AS patients and non-AS controls (adjusted HR = 1.07; 0.84–1.37), with increasing age and cancer serving as significant risk factors for incidental HZ [ 10 ]. In the case of PsA, recent studies mostly discuss the risk of HZ in relation to baseline immunosuppressive treatments [ 11 , 12 ], but a previous study also relying on the CHS database demonstrated that the risk of HZ in an untreated PsA cohort without previous Zostravax ® vaccination is 9.21/1000 patient-years [ 13 ], which is somewhat higher than that in the general population, which is around 7–10/1000 after 50 years of age [ 14 ].…”

“…While most of the studies on this subject thus far included only RA patients, some studies also included patients with psoriasis (PsO) [ 24 ] and psoriatic arthritis (PsA) [ 12 , 13 , 25 ]. Of these studies, some implicate anti-TNF-α therapy in augmenting HZ risk [ 11 , 12 ], while others find no association between HZ events and therapy with bDMARDs alone in these patients [ 13 , 24 , 25 ].…”

Burden of Herpes Zoster Among Patients with Psoriasis in the United States

“…Patients on interleukin inhibitors had lower or similar HZ incidences to the PsO– cohort, while those on any other therapy had higher HZ incidences than the PsO– cohort. Other studies have reported that HZ risk is increased in patients taking systemic corticosteroids [ 13 , 15 , 16 ], TNF-alpha inhibitors [ 12 , 16 ], JAK inhibitors [ 15 , 16 ], and various combination treatments [ 13 – 16 ], but not in those on interleukin inhibitors [ 13 , 15 , 16 ], acitretin [ 16 ], or phototherapy [ 14 , 16 ].…”

“…Since many of these treatments target the immune system, patients are at increased risk of infection [ 5 – 7 ], including herpes zoster (HZ). Various studies have reported that patients with PsO are at increased risk of HZ [ 8 – 11 ], and that this risk varies by medication class [ 12 – 16 ].…”