The Risk of Malignancy in Patients With Secukinumab-treated Psoriasis, Psoriatic Arthritis and Ankylosing Spondylitis

Analysis of Clinical Trial and Postmarketing Surveillance Data With Up to Five Years of Follow-up

M. Lebwohl; A. Deodhar; C.E.M. Griffiths; M.A. Menter; D. Poddubnyy; W. Bao; V. Jehl; K. Marfo; P. Primatesta; A. Shete; V. Trivedi; P.J. Mease


The British Journal of Dermatology. 2021;185(5):935-944. 

In This Article

Abtract and Introduction


Background: Data on the use of biologic therapy and malignancy risk are inconsistent due to limited long-term robust studies.

Objectives:To assess the malignancy risk in patients with secukinumab-treated psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS).

Methods: This integrated safety analysis from both the secukinumab clinical trial programme and postmarketing safety surveillance data included any patient receiving at least one approved dose of secukinumab with a maximum of 5 years of follow-up. Safety analyses evaluated the rate of malignancy using exposure-adjusted incidence rates [EAIR; incidence rates per 100 patient treatment-years (PTY)]. Standardized incidence ratios (SIRs) were reported using the Surveillance, Epidemiology, and End Results Program (SEER) database as a reference population. Crude incidence of malignancy was also reported using postmarketing surveillance data.

Results: Safety data from 49 clinical trials with secukinumab-treated patients were included: 10 685 patients with psoriasis, 2523 with PsA and 1311 with AS. Across indications over a 5-year period, the EAIR of malignancy was 0·85 per 100 PTY [95% confidence interval (CI) 0·74–0·98] in secukinumab-treated patients, corresponding to 204 patients per 23 908 PTY. Overall, the observed vs. expected number of malignancies from secukinumab clinical trial data were comparable, as indicated by an SIR of 0·99 (95% CI 0·82–1·19) across indications. The estimated crude cumulative incidence reporting rate per 100 PTY for malignancy was 0·27 in the postmarketing surveillance data across indications with a cumulative exposure of 285 811 PTY.

Conclusions: In this large safety analysis, the risk of malignancy was low for up to 5 years of secukinumab treatment. These data support the long-term use of secukinumab in these indications.


Secukinumab is a fully human IgG1 antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin (IL)-17A, reducing IL-17A-mediated contributions to autoimmune and inflammatory diseases.[1–4] Secukinumab is currently approved for the treatment of moderate-to-severe psoriasis (adult and paediatric), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis. Secukinumab has a proven favourable safety and tolerability profile for up to 5 years of treatment in a clinical trial setting, and almost 400 000 patient-years of cumulative exposure in a postmarketing setting.[5,6] Furthermore, a favourable safety profile has been demonstrated in the real world setting, consistent with that of Phase III clinical trials.[7,8]

Increased risk of malignancies linked to underlying chronic inflammation has been reported in systemic inflammatory diseases.[9] Chronic inflammation in these diseases can promote tumorigenesis through cytokine and chemokine production, DNA damage and epigenetic alterations.[10,11] Psoriasis and AS are generally associated with a small risk of lymphoma, particularly Hodgkin lymphoma, and this is increased in those with more severe disease.[12–14] While there does not seem to be an increased risk of overall malignancy in patients with PsA linked to underlying chronic inflammation of the disease, some evidence suggests increased risk for lymphoma.[9] Moreover, up to 30% of patients with PsA have concomitant psoriasis.[15]

In addition to an increased risk of malignancies linked with chronic inflammation, immunosuppressive and immunomodulatory therapies used in autoimmune diseases have been associated with an increased risk of specific cancers, including lymphomas and nonmelanoma skin cancers (NMSCs).[16–18] A previous medical history of malignancy must be considered when selecting the optimal therapy for patients.[19] Tumour necrosis factor-α-targeted biologic therapies (TNFi) contain a warning about lymphoma and other malignancies in their prescribing information, and the US Food and Drug Administration (FDA) have previously issued a black box warning for the use of TNFi and the risk of both non-Hodgkin lymphoma and leukaemia.[20] Additionally, using gene expression analysis as a proxy for downstream effects of TNFi, a recently presented transcriptomics study indicated that TNFi may worsen the prognosis for melanoma and sarcoma.[21] In contrast to these data, a consensus panel of experts concluded that the overall risk of malignancy (including lymphoma) was not increased in TNFi-treated patients with rheumatoid arthritis (RA).[22] This is further supported by registry data indicating that patients with RA with a prior malignancy receiving TNFi do not have an increased risk of future incidence of malignancy.[23] Differences in pathophysiological mechanisms between diseases and variations in study design, sample sizes and follow-up duration may contribute to the inconsistencies observed in the literature.

The relationship between IL-17A and tumour immunopathology is complex. T helper (Th)17 cells and Th17-associated cytokines have been shown to have both pro- and antitumorigenic functions in preclinical studies.[24] However, secukinumab clinical studies have reported low exposure-adjusted incidence rates (EAIR) of malignancies across psoriasis, PsA and AS indications.[6,25,26] The 2017 European S3-Guidelines highlighted that while no increase in risk of malignancy has been reported in Phase III clinical trials with secukinumab as compared with placebo or active comparators, no conclusions can be drawn. This is due to both a lack of long-term safety data and data from patients with a history of malignancies.[27] Here, we report malignancy risk in secukinumab-treated patients for up to 5 years in three approved indications, using both clinical trial and postmarketing safety surveillance data.