. 2021 Jan 19;84(6):1652–1666. doi: 10.1016/j.jaad.2021.01.047

Table II.

Review of data on systemic immune targeting therapies and vaccines (see Table 2 in van Riel and de Wit¹²)

Drug	Type of vaccination	Adverse events	Effects on immunity	Level of evidence
Systemic corticosteroids (prednisone)	Influenza26, 27, 28, 29, 30, 31, 32, 33, 34^,⁷³^,⁷⁵^,⁸²^,¹¹³^,¹¹⁶^,¹²¹ PPSV23³⁵^,³⁶^,¹⁰¹^,¹¹⁷^,¹¹⁹^,¹²⁰ Hepatitis B³⁷ HPV³⁸ Herpes/varicella zoster (LZV)³⁹^,⁴⁰^,¹⁴⁵ Yellow fever⁴¹	Safe, generally well tolerated. Increased frequency of moderate/severe local reactions compared to healthy control individuals have been observed; as well as a few reports of increased incidence of clinical and/or biochemical parameters of disease flare³⁰ or increased herpes zoster risk observed in patients on immune-suppressive therapy³⁹	Variable effect on immunity: adequate seroprotection and/or no significant suppression of response in several studies and associated with doses up to <10-20 mg/day.³⁷^,³⁸ Reduced seroconversion rates and/or impaired immune response/humoral response noted in a number of studies and, in particular, associated with a high-dose regimen of >20 mg/day.²⁷^,²⁹^,³⁵^,¹¹⁶ In VZV, long-term seroprotection for VZV at the 2-year follow-up was also observed.⁴⁰^,¹⁴⁵	A-B
Methotrexate	Influenza: trivalent,⁴²^,⁴³^,⁷⁹^,⁸⁰^,¹⁴⁶ pandemic (A/H1N1)⁴⁴^,⁴⁵^,⁷³^,⁷⁶^,⁷⁸^,82, 83, 84 PPSV23⁴³^,¹¹¹ PCV7/13⁴⁶^,¹²⁰^,¹⁴³ HAV⁸⁶^,⁹⁹ HBV¹⁰⁰ Tetanus/diphtheria¹⁰² MMR¹^,47, 48, 49^,⁷⁴ Herpes/varicella zoster (LZV,³⁹^,50, 51, 52^,⁸⁵^,⁹³^,¹⁴⁵ RZV⁹²) Yellow fever53, 54, 55, 56^,¹²⁹	Safe, generally well tolerated with both nonviral and live-attenuated/live vaccines⁷^,⁵⁶^,⁵⁷^,^∗^,^† Rare risk of systemic rash and fever with live-attenuated/live vaccine (ie, MMR⁴⁸^,⁴⁹ and HZV³⁹^,¹⁴⁵)	Variable effect on immunity: Most studies involving live-virus vaccines showed no significant effect on children and adult populations and satisfactory vaccine response/adequate seroprotection with a methotrexate dose of 10-25 mg/week. There is some support for improved response with temporary discontinuation and/or second dose. Nonviral vaccine is overall associated with a negative effect on immunogenicity, including reduced humoral response and insufficient protection with a single dose, with the exception of HBV (no significant effect).⁸⁶^,⁹⁹^,¹⁰⁰	A-B
Azathioprine	Influenza: trivalent,³²^,58, 59, 60 pandemic (A/H1N1)⁶¹^,⁶²^,⁸²^,⁸⁴ PPSV23¹¹⁰^,¹¹⁸ PCV13⁶³^,¹¹⁸ HAV¹³¹ HBV⁹⁷^,¹⁰⁰ Tetanus, pertussis¹⁰⁷ Herpes/varicella zoster (LZV)³⁹^,64, 65, 66^,⁹² RZV⁹² Yellow fever⁶¹	Safe, consistently well tolerated with nonviral vaccines and live-attenuated/live vaccines	Variable effects on immune response for nonviral and live-attenuated/live vaccines described. Most studies report blunted to impaired immunogenicity for nonviral and live vaccines (eg, reduced humoral response). Comparable response to healthy control individuals also has been observed in pandemic influenza strains⁶¹^,⁸² and HAV¹³¹	B
Cyclosporine	Influenza: trivalent⁶² Pandemic (A/H1N1)⁴⁴^,⁶¹^,⁸⁴ Herpes/varicella zoster (LZV)³⁹^,¹⁴⁵ Yellow fever⁶¹ PPSV23⁷² HAV⁶⁷ Tetanus toxoid⁷²	Safe, consistently well tolerated with nonviral vaccines and live-attenuated/live vaccines.	Consistent findings describing overall negative effect on immune response with nonviral and live-attenuated/live vaccines (ie, reduced recall humoral response, reduced rates of seroconversion, in vitro cellular immune response).	A-B
Mycophenolate mofetil	Influenza: trivalent,⁵⁹^,⁸⁷ pandemic (A/H1N1)⁶⁸^,⁸⁴^,⁸⁸ PPSV23⁷² Tetanus toxoid⁷² Yellow fever⁶¹	Safe, generally well tolerated (few reports of mild adverse effects)	Variable effects on immune response described in the literature. Most studies describe reduced immunogenicity/reduced humoral response with nonviral vaccines and worse with doses >2 g/day. Some support for antibody response comparable to healthy control individuals or nonsignificantly reduced/improved response with second dose. No studies evaluating immunogenicity in live-attenuated or live vaccines.	A-B
JAK inhibitors	Influenza (trivalent)⁹⁵ PPSV23⁸⁹^,⁹⁴^,⁹⁵ Tetanus toxoid⁸⁹^,⁹⁵ Herpes/varicella zoster⁶⁹^,⁹¹^,⁹²	No reports of clinically significant adverse effects	Evidence is limited. Overall consistently preserved immunogenicity with nonviral and live-attenuated/live vaccine (ie, LZV^†); sustained/long-term seroprotection may be inadequate.^‡	B

HAV, Hepatitis A vaccine; LZV, live zoster vaccine; MMR, measles, mumps, rubella; PPSV, pneumococcal polysaccharide vaccine; RZV, recombinant zoster vaccine; VZV, Varicella zoster virus.

^∗

No significant adverse effects and no reports of increased clinical or laboratory index of disease activity. No exacerbation of disease activity in a number for autoimmune/inflammatory diseases. No adverse effects in function or graft failure in solid organ transplant recipients. One case report of fatal vaccine-associated viscerotropic disease.⁷⁴^,⁸³

^†

In a cohort of patients vaccinated 2 to 3 weeks before starting tofacitinib treatment.

^‡

Diminished humoral response to tetanus toxoid vaccine at week 12 and only 60% mounting 4-fold response to tetanus toxoid vaccine in patients with psoriasis on JAK inhibitors.