Table 3.
Trial data on systemic medications and the risk of infection
| Trial | Trial Type | Type of infectious risk assessed | Number | |
|---|---|---|---|---|
| Cyclosporine | Grattan et al. 54 | Randomized, double‐blind, placebo controlled | URTI | 10% of 20 vs. not reported/10 placebo |
| Flu‐like symptoms | 15% of 20 vs. not reported/10 placebo | |||
| Vena et al. 125 | Randomized, double‐blind, placebo controlled | Infections | 3.2% of 62 vs. 8.6% of 35 | |
| Karanikolas et al. 126 | Non‐randomized, unblinded, ADA vs. CsA | Any infection | 3.5% CsA of 57 vs. 10.3% of 58 ADA | |
| Any serious infection | 0% of 57 CsA vs. 1.7% of 58 ADA | |||
| URTI | 1.8% of 57 CAsA vs. 8.6% of 58 ADA | |||
| Lai et al. 127 | Randomized, double‐blind, placebo controlled | Infections (UTI a ) | 5.6% of 18 vs. 0% of 18 placebo | |
| Mycophenolate mofetil | Beissert et al. 128 | Randomized, non‐blinded, methylpred + MMF vs. methylpred + AZA | Grade 3 Infections (severe) b | 11% of 35 Methylpred + MMF vs. 0% of 38 Methylpred + AZA |
| Grade 4 Infections (life threatening) | 0% of 35 Methylpred + MMF vs. 3% of 38 Methylpred + AZA | |||
| Beissert et al. 62 | Randomized non‐blinded, Prednisone (Pred) + MMF vs. Pred monotherapy c | Nasopharyngitis | 12% of 58 Pred + MMF vs. 0% of 36 Pred | |
| URTI | 10% of 58 Pred + MMF vs. 3% of 36 Pred | |||
| Influenza viral | 0% of 58 Pred + MMF vs. 3% of 36 Pred | |||
| LRTI | 3% of 58 Pred + MMF vs. 0% of 36 Pred | |||
| Overall Infections | 59% of 58 Pred + MMF vs. 36% of 36 Pred P = 0.04 | |||
| Akhyani et al. 129 | Randomized, open‐label MMF vs. MTX | Infections d | 0% of 20 vs. 0% of 18 MTX | |
| Ioannides et al. 130 | Randomized, non‐blinded, methylpred vs. methylpred + MMF | Internal Infection | 8% of 24 Methylpred + MMF vs. 4% of 23 Methylpred (P = 1.0000) | |
| Zhou et al. 131 | Open‐label | Infection | 0% of 23 | |
| Azathioprine | Meggitt et al. 68 | Randomized, double‐blind, placebo controlled | LRTI | 5% of 41 vs. 0% of 20 |
| URTI | 5% of 41 vs. 5% of 20 | |||
| Berth‐Jones et al. 67 | Double blind, randomized, placebo crossover | URTI | 20% of 25 vs. 8% of 25 | |
| Schram et al. 69 | Randomized, single blind compared to methotrexate | Infection | 70% of 22 vs. 64% of 20 MTX | |
| Moderate intensity infection | 36% of 22 vs. 25% of 20 MTX | |||
| Methotrexate | METOP 73 | Randomized, double‐blind, placebo‐controlled | Any infection | 44% of 91 weeks 0–16 and 41% of 76 weeks 16–52 vs. 45% of 29 weeks 0–16 placebo |
| Serious infection | 0% of 91 vs. 3% of 29 placebo | |||
| Pasnoor et al. 74 | Randomized, double‐blind, placebo‐controlled | Infection | 16% of 175 vs. 11% of 161 placebo | |
| Kingsley et al. 75 | Randomized, double‐blind, placebo‐controlled | Respiratory tract infection | 28% of 109 vs. 22% of 112 placebo | |
| Apremilast | UNVEIL 84 | Double‐blind, placebo‐controlled, 52 weeks | Nasopharyngitis | 10% of 211 vs. N/A placebo |
| URTI | 7% of 211 vs. N/A placebo | |||
| LIBERATE 85 | Randomized, double‐blind, Aprem vs. Enbrel vs. placebo with Aprem extension a | URTI | 7% of 74 vs. 7% of 73 placebo/Aprem | |
| Nasopharyngitis | 3% of 74 vs. 6% of 73 placebo/Aprem | |||
| Bronchitis | 5% of 74 vs. 1% of 73 placebo/Aprem | |||
| Bissonette et al. 86 | Randomized, double‐blind, placebo‐controlled | URTI | 26% of 53 vs. 14% of 50 placebog | |
| Bronchitis | 6% of 50 vs. 0% of 50 placebo | |||
| ESTEEM 1 87 | Randomized, double‐blind, placebo‐controlled | URTI |
10% of 560 EAIR/100 py = 37.6 vs. 7% of 282 EAIR/100 py = 27.3 placebo |
|
| Nasopharyngitis |
7% of 560 EAIR/100 py = 26.6 vs. 8% of 282 EAIR/100 py = 30.1 |
|||
| ESTEEM 2 88 | Randomized, double‐blind, placebo‐controlled | URTI | 5% of 272 EAIR/100 py = 17.3 vs. 4% of 136 EAIR/100 py = 16.7 | |
| Nasopharyngitis |
7% of 272 EAIR/100 py = 27.3 vs. 4% of 136 EAIR/100 py = 16.9 placebo |
|||
| Any type of infection | 25% vs. 21% placebo | |||
| Vossen et al. 88 | Randomized, double‐blind, placebo‐controlled | Common cold | 26% of 15 vs. 20% of 5 placebo | |
| Thalidomide | Droitcourt et al. 132 | Randomized, double‐blind, placebo‐controlled | Cough and fever | 5% of 20 vs. 0% of 19 placebo |
| Kaur et al. 133 | Randomized, double‐blind, thalidomide vs. prednisolone | Infection d , e | 0% of 30 vs. 0% of 30 prednisolone | |
| Lazzerini et al. 134 | Randomized, double‐blind, placebo‐controlled | Infection d | 0% of 12 vs. 0% of 31 placebo | |
| Hamuryudan et al. 135 | Randomized, double‐blind, placebo‐controlled | Infection d | 0% of 63 vs. 0% of 32 placebo |
URTI, upper respiratory infection; ADA, adalimumab; CsA, Cyclosporine; UTI, urinary tract infection; MEP, methylprednisolone; MMF, mycophenolate mofetil; AZA, azathioprine; Pred, prednisone; LRTI, lower respiratory infection; MTX, methotrexate; Aprem, apremilast; EAIR, exposure‐adjusted incidence rate; py, patient years.
a
Urinary tract infection.
b
Three infections were URTIs; one infection was recurrent HSV.
c
No patients withdrew due to infection.
d
No infections reported in paper.
e
One patient had amoebic dysentery within 2 weeks of initiation of study and stopped therapy.