Table 2 Studies which demonstrated an increased incidence of malignancy associated with systemic immunosuppressive therapy in autoimmune diseases

Cyclophosphamide

1

461 patients with RA treated with CYP found 5 bladder cancers developed during 5-year follow-up compared to the expected incidence for the general UK population (0.38)

[22]

2

15 malignancies developed in 81 RA patients treated with CYP with a fourfold increase in the expected risk of malignancy compared to matched control RA patients not on cytotoxic therapy

[23]

3

119 patients with RA treated with CYP were compared to 119 matched controls that found 37 malignancies in 29 patients and 16 malignancies in 16 patients in the control (p < 0.05); the major differences were in the number of bladder and NMSC observed (6 and 8, respectively) in the CYP-treated group and none in the control

[24]

Azathioprine

1

Analysis of data from 643 patients with RA found a 13-fold increase in NHL (whether treated with AZA or CYP)

[25, 26]

2

202 patients with RA treated with AZA compared to 202 RA patients without found a tenfold increase in NHL in patients treated with AZA and a fivefold increase in RA patients without therapy compared to the general population approximately 12-year follow-up

Methotrexate

1

458 RA patients treated with MTX found a fivefold increase in NHL and threefold increase in melanoma compared to the general population with age standardisation; however, risk was increased with prior CYP exposure prior to MTX (2.5-fold increase)

[27]

Cyclosporine

1

In 1,252 patients with psoriasis followed up for 5 years, it was found that 47 patients (3.8%) developed malignancies; the standardised incidence ratio was 2.1 as compared with the general population; the study found a sixfold higher incidence in skin malignancies

[28]

Biologics

1

A RCT of 619 patients with RA treated with adalimumab and with previous MTX exposure found 4 adalimumab-treated patients developed NMSC, 1 non-Hodgkin's lymphoma and 1 adenocarcinoma

[29]

2

In a JIA cohort of 7,812 treated with TNF inhibitors, an increased risk of malignancy in JIA patients compared to children without JIA was found; however, any increased risk of malignancy in patients treated with TNF inhibitors was not found

[30]

An epidemiologic study of non-transplant patients treated with systemic immunosuppression treated for greater than 3 months with AZA, CYP or chlorambucil found an increase in NHL by 11-fold, SCC by fivefold and carcinoma of the bladder by fourfold compared to the general population

[25]