The Oncology: Disease Modifying Anti-Rheumatic Drug Interface: A Cross-Specialty Review

1. Introduction

Historically the oncology- immune mediated inflammatory disease therapeutic interface has been one of alignment with the use of cytotoxic agents such as cyclophosphamide and methotrexate in both disease types. This interface became more nuanced in the past 5 decades with the Nobel prize winning development of mono-clonal antibodies by Milstein and Kohler [1]. Since then, a transformative exponential rise has occurred in the armamentarium of monoclonal antibodies in both disease types (Figure 1, Table 1). B-cell depletion therapies such as rituximab have pivotal roles in both spheres, while disease modifying antirheumatic drugs (DMARDs) are limited to one sphere but their potentially deleterious effects on anti-tumor immunity have led to concerns about an increased risk of malignancy for patients [2,3,4,5]. This concern is even greater in patients with a history of cancer, where an increased cancer relapse rate could be a bystander effect of an otherwise quality of life transforming therapy.

Cancer and immune mediated inflammatory diseases are among the most common and increasing non-communicable diseases globally [6]. Clinicians can encounter clinical dilemmas of prescribing DMARDs in patients with a prior malignancy. While the available evidence does not support a deleterious effect in patients with cancer, the available evidence has shortcomings, most studies include long term survivors rather than patients with newly diagnosed cancer [7]. Patients with cancer were often excluded from pivotal studies. Furthermore, the range of available personalised therapies is expanding precluding even expert panels from formulating universal recommendations [8]. Available median follow up in many studies is limited (4.52 years in one recent metanalysis [9]) limiting reassurance for patients such as those with breast cancer where delayed relapse (5 years or more post diagnosis) is common. Finally, to address the informational needs of patients in these therapeutic dilemmas we need their insights. However the patient voice is missing from many of the available studies in this area. In 2025 the first ever study of the perspectives of patients with rheumatoid arthritis and concomitant cancer was published [10].

In light of the above shortcomings, it prompted us to establish a multidisciplinary group to review this area. This article is a narrative, non-systematic review of the literature across dermatology, rheumatology, respiratory, and gastroenterology. Relevant publications were identified through searches of PubMed and other search engines, supplemented by manual review of reference lists of key articles. Studies were selected based on relevance to the topic. Where available, registry and real-world cohort data are prioritised because malignancy outcomes are uncommon and often have long latency periods (Table 2).

Randomised clinical trials and their extensions can support short-term safety signals but are frequently underpowered for malignancy endpoints and commonly exclude patients with recent cancer (Table 3). As a result, clinical trial data are usually most useful when they explicitly include patients with a prior malignancy or report longer follow-up in relevant subgroups (Table 2) [11]. In our review we have incorporated relevant registry data bases and if clinical trials were included we favored open label extensions or longer periods of reporting (Table 2 and Table 3).

2.0. Malignancies in Patients with Auto-Immune Disease

2.1. Psoriasis

Malignancy is an important consideration in patients with immune-mediated conditions such as psoriasis. Whether psoriasis confers an independent increase in malignancy risk, or whether malignancy represents a comorbidity, particularly for site-specific cancers, has been examined in epidemiological studies and subsequent systematic reviews and meta-analyses [1]. The biological plausibility of an association is supported by the role of chronic inflammation in psoriasis and its contribution to carcinogenesis [1,2].

The most consistently reported associations are with immunosensitive malignancies, including lymphoma and skin cancers, although many data sources are not derived from prospective registry studies [3,4,5,6,7,8]. Other reported site-specific cancers include those of the oral cavity, larynx, pharynx, colon, lung, and kidney [3,8,9,10,11,12]. A 2015 systematic review found no increased overall malignancy risk across all cancers, lymphoma, melanoma, prostate, colorectal, and breast cancer other than non-melanomatous skin cancer [13]. Observed excess risks in other studies [3,4,5,6,7,8] may reflect treatment exposures, lifestyle factors, or surveillance bias.

The first meta-analysis by Trafford et al. evaluating cancer mortality in psoriasis demonstrated substantial attenuation of risk after adjustment for smoking, alcohol use, and obesity [1]. However, another systematic review and meta-analysis reported increased risks of selected solid tumours (respiratory tract, upper aerodigestive tract, urinary tract, and liver cancers), haematological malignancies (non-Hodgkin lymphoma), and skin cancers (squamous cell carcinoma and basal cell carcinoma) [14]. Smoking prevalence is high among patients with psoriasis [15], and certain site-specific cancers, including oesophageal and liver cancer, are independently associated with obesity, smoking, and alcohol consumption [16].

Older systemic therapies, including PUVA, cyclosporine, and possibly methotrexate, have also been associated with increased malignancy risk [17,18,19]. Adjustment for lifestyle factors may be methodologically complex, as these variables may lie on the causal pathway. Notably, few studies report duration of treatment exposure, underscoring the need for prospective pharmacovigilance registries.

Overall, observational evidence supports an association between psoriasis and selected malignancies, but whether psoriasis independently increases malignancy risk remains uncertain when treatment exposure, lifestyle confounding, and surveillance bias are considered [1].

2.2. Systemic Rheumatic Disease

Rheumatic diseases and malignancy have a complex bidirectional association. Dermatomyositis, polymyositis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, and systemic sclerosis are linked to increased cancer risk in and of themselves, and may occasionally represent paraneoplastic autoimmunity. Furthermore, immunosuppressive therapies used in these conditions can contribute to malignancy risk [20]. Malignancies can initially manifest with musculoskeletal symptoms affecting joints, muscles, or peri-articular tissues. Hematologic cancers, particularly leukaemia and lymphomas, are most frequently implicated, although solid tumours may also give rise to paraneoplastic rheumatic features [21]. Additionally, oncologic treatments can precipitate immune-mediated rheumatic syndromes.

Across multiple meta-analyses and large cohort studies, systemic rheumatic diseases are consistently associated with a modest to substantial increase in overall malignancy risk, although the magnitude and tumor type vary by condition [20,22]. Rheumatoid arthritis and systemic lupus erythematosus confer a small but significant elevation in overall cancer risk with a predominance of lymphoproliferative malignancies and lung cancer [23,24]. Systemic sclerosis is associated with a higher relative risk particularly for lung and selected solid organ cancers [25]. The strongest associations are observed in idiopathic inflammatory myopathies, especially dermatomyositis, where overall cancer risk is markedly elevated, with increased incidence across a broad range of solid tumours [26]. Extended myositis antibody panels further help the risk of malignancy stratification with Anti-TIF1-γ and anti-NXP2 having the strongest associations. Sjögren’s disease and ANCA-associated vasculitis also demonstrate increased overall malignancy risk, notably driven by non-Hodgkin lymphoma and selected solid tumours [27].

Collectively, these data highlight important disease-specific patterns of cancer susceptibility that have implications for risk stratification and malignancy surveillance in rheumatology practice.

2.3. Inflammatory Bowel Disease

The risk of colorectal cancer is increased in patients with IBD compared to the general population. A population based cohort study of over 96,000 patients with ulcerative colitis found that compared with those without UC, those with UC are at increased risk of developing colorectal cancer, are often diagnosed with less advanced colorectal cancer and are at increased risk of dying from it [28]. Regarding UC the duration, extent and activity of disease affect the likelihood of colorectal cancer developing [28,29,30,31].

Studies have shown a comparable risk of colorectal cancer in chronic Crohn disease involving the colon to UC [32,33]. A 1990 population based study found the relative risk of colon cancer was 2.5 in CD overall but if their disease affected the colon only the relative risk increased to 5.6 [32]. These findings are consistent across studies [34]. Other malignancies which have been reported in patients with CD liver, pancreas, lung, prostate, testicular, kidney and (squamous cell) skin cancers; endocrine tumours and leukaemia [35]. The strength of these associations is unclear however, one of the most consistent findings in other studies is an association with haematologic malignancies [35,36].

2.4. Chronic Airway Inflammatory Disease

Chronic airway inflammatory disorders such as asthma and Chronic obstructive pulmonary disease (COPD), although not prototypical immune-mediated inflammatory diseases, provide a relevant comparator for understanding malignancy risk in conditions characterised by chronic immune dysregulation and increasingly treated with biologic or targeted therapies.

Across large population-based studies, asthma is associated with a modest overall increased risk of malignancy, with reported hazard ratios for incident malignancy ranging from 1.19 to 1.44 across diverse populations and healthcare systems [37,38,39,40,41].

The most consistent and biologically plausible signal relates to lung cancer. Multiple cohort studies, including—the HUNT study- demonstrate higher lung cancer incidence among adults with active or partially controlled asthma compared with those without asthma, even after adjustment for potential confounders [42]. This association is observed in both smokers and never-smokers, although effect estimates are higher in current or former smokers [39,41,43]. A recent mendelian randomisation analyses further support a potential causal association between asthma genetic liability and lung cancer [43]. Associations with breast and stomach cancer have also been reported previously [37,44] potentially reflecting chronic inflammation pathways involved in asthma [45]. However, findings across studies are heterogeneous, and some studies report no association between asthma and overall cancer risk [46,47]. Further research is required to clarify underlying mechanisms and to better define risk estimates for non-lung cancers [38,48].

Similar observations have been made in COPD, where chronic airway inflammation confers an increased lung cancer risk independent of smoking, reinforcing the broader concept that persistent airway immune activation contributes to carcinogenesis [49].

3.0. Biologic and Targeted Therapies in the Context of Malignancy

Immunomodulatory agents and biologic therapies are used by many medical specialties for immune mediated disease and their use is rapidly expanding. They are targeted therapies which downregulate these overactive immune pathways, delivering improved outcomes but immunologic effects can be of concern in the setting of malignancy. Oncologists are often consulted when patients with a past or current malignancies require these systemic treatments. This complex patient cohort require careful consideration regarding the commencement or cessation of newer biologic treatments.

Generally, immunosuppressants may contribute to the development of new cancers and the recurrence of existing ones through several mechanisms, including reduced immunosurveillance [50], enhanced activity of oncogenic viruses [51], and direct DNA alteration [52]. These mechanisms vary significantly across different immunosuppressants and cancer types. The interplay between the chosen biologic agent, their specific malignancy type and the impact on their quality of life are all essential factors which require considered deliberation. There is often no direct, high-level evidence which exists to address these concerns. This review aims to explore the interface between medical specialities and oncologists for those patients with a chronic medical diagnosis requiring treatment with a biologic agent and a history or malignancy.

3.1. Drug Class Evidence

The available evidence for malignancy risk differs across drug classes and diseases, and is most robust where long-running registries and real-world cohorts exist. In contrast, randomised trials often have short follow-up and frequently exclude patients with recent malignancy, limiting their ability to quantify malignancy incidence or recurrence risk [53].

3.1.1. TNF-Inhibitors in Dermatology

Tumour necrosis factor (TNF) is a cytokine which exerts necrotising effects when exposed to tumour cells in vitro and is produced by activated T cells and macrophages. TNF is now known to have pro and antitumorigenic effects which are dependent on unique conditions, the type of producer and responder cell, the type of TNF receptor involved and on the tissue environment. TNF-inhibitors are a widely used treatment for inflammatory dermatoses, with the majority of data being in those patients with psoriasis. As previously discussed, patients with psoriasis may have an increased risk of malignancy, particularly nonmelanoma skin cancers and lymphomas [54]. A 2020 systematic review and meta-analysis of 112 studies and over 2 million patients found the overall prevalence of cancer in patients with psoriasis was 4.78%. They noted no increased risk of cancer in those patients treated with a biologic agent however, they did not include detail on the type of biologic agent [54]. The dermatology literature indicates that TNF inhibitors have been associated with increased risk of lymphoma and nonmelanomatous skin cancers [55,56,57]. A retrospective cohort study of Korean patients with RA or psoriasis taking TNF-inhibitors found no increase of incident cancer but did find an increased risk of lymphoma and leukaemia, particularly for infliximab [58].

The Psoriasis Longitudinal Assessment and Registry (PSOLAR) which is a US-based registry of over 12,000 patients found that TNF-inhibitor treatment for over 12 months increased the risk of lung cancer. However, they report wide confidence intervals and low event numbers [55]. Further research from the PSOLAR registry indicated no statistically significant risk of malignancy when individual anti-TNF agents were considered [59]. A systematic review of psoriasis patients completed in 2018 found no increase in malignancy, except for nonmelanomatous skin cancers, with TNF-inhibitors when compared to the U.S. population [60]. The ESPRIT registry similarly showed no significant increased cancer risk in patients with psoriasis treated with TNF-inhibitors over a 7 year period [61]. Cross-speciality evidence including phase II trials demonstrating the efficacy of infliximab in metastatic renal cell cancer, show the potential for underutilisation of these medications because of safety concerns and poor dissemination of relevant data [62]. An umbrella review of potential cancer risk associated with common medications included TNF-inhibitors but noted the pooled estimate in a larger scale meta-analysis did not demonstrate an increased risk (RR 0.95) [63].

Overall, available dermatology registry and synthesis data do not demonstrate a consistent increase in overall malignancy risk with TNF inhibitors in psoriasis, with the most consistent signals relating to nonmelanomatous skin cancer and selected site-specific outcomes [55,56,59,60,61]. There have been no prospective or randomised studies where patients with psoriasis and a history of malignancy are treated with an anti-TNF agent.

3.1.2. TNF-Inhibitors in Gastroenterology

Generally gastroenterologists use TNF-inhibitors to manage inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis. TNF-inhibitor data for IBD patients should be interpreted in the context of their use with thiopurines. It has been established that receiving thiopurines carries an increased risk of lymphoproliferative disorders, particularly when prescribed in addition to TNF-inhibitors [64,65]. A metanalysis in 2008 found no increased incidence of malignancy though patients with a history of malignancy were not included in the studies [66]. Axelrad et al. performed a retrospective analysis of 333 individuals with IBD with a history of cancer and noted no associated increased risk of incident cancer compared with patients who had not received an TNF-inhibitor or antimetabolite [67]. Comparable findings from a 2014 systematic review did not find an increased risk of malignancy in patients with IBD. Though patients with a history of malignancy were not included and the follow up period was maximum 1 year [68]. Similarly, pooled analysis of clinical trials for adalimumab found no increased cancer risk, unless it was co-prescribed with another immunomodulator which is reassuring for use as a monotherapy [69].

In the TREAT Registry study the minimum follow up period for active patients was approximately 5 years. They found no association of systemic therapy and malignancy [70]. A large Danish study found no increased overall cancer risk in IBD patients treated with TNF-alpha inhibitors after a median follow-up of 3.7 years. Current evidence indicates that TNF blockade alone does not substantially elevate long-term cancer risk, even with follow-up extending to 19 years [71]. Large cohort and synthesis studies continue to show no clear increase in overall incident cancer with anti-TNF monotherapy in IBD and the most consistent signals relate to nonmelanomatous skin cancer and potentially melanoma [72]. A recent retrospective review observed a low prevalence rate of cancer, even in the context of a wide variation of biologic and immunosuppressive treatments being used [73]. In patients with pre-existing malignancy, the most directly applicable evidence is observational, and available IBD data do not show an excess of new cancers among those exposed to anti-TNF agents [67].

3.1.3. TNF-Inhibitors in Rheumatology

Rheumatic diseases and cancer share complex bidirectional associations. Disorders such as dermatomyositis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) carry an elevated malignancy risk and, in some cases, may arise secondary to cancer-induced autoimmunity [74]. There is a paucity of data regarding cancer risk in patients with psoriatic arthritis (PSA) [54] but it is generally accepted that inflammatory arthropathies are associated with malignancy in and of themselves [75].

TNF-inhibitors are an essential biologic agent for the treatment of rheumatoid arthritis, psoriatic arthritis and spondyloarthropathies. The German biologics register (RABBIT) was set up to investigate malignancies in patients with RA receiving systemic therapy. They found no significant difference in the either the overall incidence of malignancies or recurrent malignancies in patients exposed to TNF-inhibitors or anakinra [76]. The British Society for Rheumatology (BSR) Biologics Register, a prospective observational study established in 2001, identified 293 patients with a prior history of malignancy treated with TNF-inhibitors and found no increased risk of incident malignancy when compared with those receiving DMARD therapy [77]. Additionally a systematic review for the 2019 update of the EULAR recommendations for the management of psoriatic arthritis did not reveal new malignancy signals for TNF-inhibitors [78].

A large cohort of RA patients from the Swedish cancer registry showed lymphoma risk was not elevated in anti-TNF treated patients when compared to other patient groups [79]. A 2006 [80] and 2011 [81] systematic review and metanalysis found TNF-inhibitors do not increase the risk of malignancy, particularly lymphoma. The 2006 review did note a significant increase in malignancy rate with higher doses of TNF-inhibitors [80]. A further study explored the incident cancer cases in over 13,000 patients between 1998 until 2005 (49,000 patient years) and found a positive association between biologic therapy and skin cancer but no association with biologic therapy and other malignancies. The biologics included with infliximab, etanercept, adalimumab and anakinra [82]. Similarly data from Swedish (Anti-Rheumatic Therapy in Sweden (ARTIS) and Danish (DANBIO) biologics registers, which included 8703 patients, found in patients with spondyloarthropathies, TNF-inhibitors were not associated with increased risks of malignancy [83]. This was noted in previous research from the DANBIO registry in 2013 for patients with RA [84]. A more recent systematic review published in 2025 similarly found no increased risk of malignancy with TNF-inhibitors though the median length of follow-up was 41 weeks (interquartile range of 24–64 weeks) [85].

A randomised non-inferiority trial comparing tofacitinib with anti-TNF therapy (median follow-up 4 years) reported an incident cancer rate of 2.9% (42/1451) in the tofacitinib group—statistically higher than anti-TNF therapy, though the absence of a conventional DMARD arm limits broader comparisons [86]. A Danish nationwide registry-based cohort study of RA patients looked at overall cancer numbers in several groups of patients taking systemic agents and found the TNF-inhibitor and bDMARD-naïve groups as comparable statistically to each other and to other RA patients taking tocilizumab/sarilumab, abatacept or rituximab [87]. Westermann et al. also reviewed the cancer recurrence risk with bDMARD treatment in patients with RA and a history of cancer (breast, colorectal, melanoma, bladder, endometrial and lung) and found no statistically significant increased hazards ratio for cancer recurrence for any type of DMARD, TNF-inhibitor or rituximab [88]. The BIOBADASER III registry data for RA patients from 2000–2023, found no increased cancer risk associated with a biologic agent or targeted synthetic DMARD when compared to TNF-inhibitors, though patients with a history of malignancy were excluded [89]. Similarly the Swedish Rheumatology Quality Register (2016–2020 prospective data) found reassuring hazard ratios for malignancy in patients receiving TNF-inhibitors, though follow up time was relatively shorter at less than 3 years [90].

The most recent EULAR guidelines recommends TNF inhibitors iin patients with a history solid organ malignancy, as it has the largest body of evidence indicating no significant association with malignancy [75]. Across rheumatology registries, TNF inhibitors have the largest evidence base in patients with prior malignancy, and recurrence signals have not been consistently demonstrated [75,76,77].

3.1.4. Anti-IL-23 Antibodies in Dermatology

The effects of interleukin(IL)-12, IL-23 and IL-17 on tumorigenesis, particularly regarding their inhibition, has not been fully elucidated [91,92]. Generally, anti-IL-23 antibodies are associated with lower rates of serious adverse events compared with TNF-inhibitors, likely reflecting their more targeted immunologic mechanism [93]. They are used by dermatology to control psoriasis and are also utilised for psoriatic arthritis. The VOYAGE 1 and 2 trials did include patients with a history of malignancy, without recurrence, for at least 5 years. Within this group of 20 patients, only two malignancies were reported following gusulkumab therapy [53].

Current evidence from large population-based studies and meta-analyses indicates that anti-IL-23 antibodies do not increase malignancy risk in patients with psoriasis or psoriatic arthritis, including those with a prior cancer history [94,95,96,97]. Overall, the incidence of total malignancies, nonmelanoma skin cancers, and other site-specific cancers in patients receiving anti-IL-23 antibodies is comparable to rates seen with TNF-inhibitors and placebo [94]. Some analysis suggests a potentially lower risk of non-Hodgkin lymphoma, hepatobiliary cancer, and basal cell carcinoma with anti-IL-23 antibody therapy [95]. The joint guideline from the American Academy of Dermatology (AAD) and the National Psoriasis Foundation (NPF) states that, while long-term data on the effects of guselkumab and other anti-IL-23 antibodies on solid organ and lymphoreticular malignancies remain limited, no safety signals have been identified to date [97].

In summary, dermatology data do not demonstrate a signal for increased malignancy with IL-23 inhibition, and limited available data in patients with prior malignancy are reassuring though numbers remain small [53,94,95,96].

3.1.5. Anti-IL-23 Antibodies in Gastroenterology

Anti-IL-23 antibodies are approved for moderate-to-severe Crohn’s disease and ulcerative colitis and are commonly used in patients refractory to TNF-inhibitor therapy [98,99,100,101].

Current evidence indicates that IL-23 inhibition does not increase malignancy risk in inflammatory bowel disease. Randomized controlled trials and meta-analyses report low rates of serious adverse events, including malignancy, with no signal of elevated cancer risk compared with placebo or other biologic classes [93,98,99,102].

Long term data is emerging but is largely from open-label extensions as opposed to registry-level population-representative data for anti-IL-23 antibody agents in IBD. The LUCENT-3 open label extension (to week 152) found malignancy occurred in 0.3% of patients without concerning safety signals [103]. Risankizumab is being examined in the ongoing FORTIFY open-label extension (approximately 3 years reported) and 2 malignancies in total have been reported, excluding nonmelanomatous skin cancer [104]. The phase 3 GALAXI trials for guselkumab and Crohn’s disease have not indicated an increased risk for malignancy at induction or maintenance phases [105]. A further systematic review including patients with UC and Crohn’s disease demonstrated reduced serious adverse events and no increase in malignancy during both induction (12 week) or maintenance (52 week maximum) phases [106].

Anti-IL-23 inhibitors are relatively new agents in gastroenterology and as such, robust registry data with detailed malignancy incidence are not yet available. Extrapolation from malignancy rates dermatology and rheumatology literature does not indicate an elevated risk [93]. The American Gastroenterological Association (AGA) notes that, while long-term population-level data remain limited, no malignancy-related safety concerns have been identified to date [107]. Importantly, although trial follow-up remains relatively short, there is no emerging signal of increased incident malignancy, and current data do not suggest excess recurrence risk in the limited cohorts including prior malignancy [99,103].

3.1.6. Anti-IL-23 Antibodies in Rheumatology

Anti-IL-23 antibodies are incorporated into treatment algorithms for psoriatic arthritis but are generally not recommended for axial disease. Findings regarding malignancy across systematic reviews have been somewhat inconsistent. A 2019 systematic review and metanalysis by Bilal et al. pooled results from 74 clinical trials and concluded that those exposed to biologic agents, compared to placebo, had an increased risk of opportunistic infections and malignancy [108]. They did not group the various biologic agents by class and included multiple rheumatologic conditions. They also included nonmelanomatous skin cancers with all other malignancies and grouped extension trials with randomised control trials. These factors may have inflated the malignancy risk for those rheumatology patients receiving these agents [108]. Taken together the interpretation of malignancy risk is challenging as it may have been overstated [108].

Subsequently a meta-analysis of 48 randomized clinical trials, including studies in rheumatology, dermatology and gastroenterology populations, found no evidence of an association between anti-IL-23 antibodies and cancer incidence, with serious adverse events occurring infrequently. The review concluded that anti-IL-23 antibodies demonstrate a favourable overall safety profile with no signal for malignancy [109]. A comprehensive review, published in the Lancet, of anti-IL-23 antibodies across chronic inflammatory diseases, including psoriatic arthritis, found accumulating long-term safety data showing comparable rates of serious adverse events and infections to placebo, with no clear signal of increased malignancy risk [93].

When analysed by drug class rather than pooled across biologics, current evidence supports a favourable malignancy safety profile for IL-23 inhibitors in rheumatology [93,109].

3.1.7. Anti-IL-17 Antibodies in Dermatology

IL-17 is a powerful pro-inflammatory cytokine and has been shown to contribute to the initiation, growth and proliferation of multiple malignancies [92]. Elevated levels of IL-17 have been associated with worse outcomes in several malignancies therefore, extrapolating from this suggests anti-IL-17 antibodies may reduce malignancy risk [92]. Kridin et al. reported that treatment with anti–IL-17 inhibitors was associated with a reduced incidence of several malignancies, including non-Hodgkin lymphoma, colorectal, hepatobiliary, and ovarian cancers, as well as melanoma and basal cell carcinoma [95].

Registry data, including findings from Psonet, have not demonstrated an association between biologic therapy and malignancy though the exact number of patients who received anti-IL-17 agents is not provided [110]. This study was limited by insufficient statistical power to assess and compare risks across specific agents or cancer types [110]. Battista et al. 2024 retrospectively reviewed 20 adult patients of which 15 had a preceding diagnosis of malignancy prior to biologic treatment. The most frequently prescribed biologic agents were anti-IL-17 antibodies (47.7%) and anti-IL-23 antibodies (36.8%) which demonstrated sustained efficacy with a favourable safety profile [111]. A pooled analysis from 28 clinical trials of secukinumab and a post-marketing safety surveillance in psoriasis, psoriatic arthritis and ankylosing spondylitis patients found the rate of malignancy was consistent with previous reports and more in depth data sets for longer time periods did not increase malignancy numbers, indicating a favourable safety profile [112]. More recent reviews of the newer anti-IL-17 antibodies, bimekizumab, have shown no increased signal for malignancy as part of their 3 year extension trial [113].

Olivares-Guerrero et al. assessed the safety profile of biologic drugs used for psoriasis in those patients included in the Spanish Registry of Adverse Events of Biological Therapy (BIOBADADERM), compared to that of adalimumab [114]. They noted that ixekizumab, secukinumab and guselkumab were associated with a lower risk of benign, malignant and unspecified neoplasms compared to adalimumab [114]. A recent study with some data for Secukinumab, found malignancy rates were low and generally reassuring [115]. Papp et al. described the outcome from a multidisciplinary expert panel and concluded that those patients with psoriasis and a history of treated solid organ tumours with favourable prognosis, have similar outcomes to those without solid organ tumours if treated with systemic biologic therapies. They highlighted that individuals with a poor prognosis in the context of solid organ tumours, the quality of life benefits of treating psoriasis may outweigh the theoretical risks [116]. Across dermatology data, IL-17 inhibition has not demonstrated an increased malignancy signal, and limited observational data in patients with prior solid organ malignancy are reassuring [111,116].

3.1.8. Anti-IL-17 Antibodies in Rheumatology

Anti-IL-17 antibodies are generally used by rheumatologists to treat psoriatic arthritis and axial spondyloarthropathies. They were included in the systematic review by Bilal et al. which concluded that those exposed to biologic agents may be at increased risk of malignancy [108]. However, subgroup analyses for individual anti-IL-17 agents did not reach statistical significance, likely due to small sample sizes and short follow-up [108]. Long-term extension trials and population-based studies in psoriasis and psoriatic arthritis, including cohorts with rheumatologic manifestations, show low exposure-adjusted malignancy rates with IL-17 inhibitors, with no signal of increasing risk with continued treatment [94]. The long-term safety of bimekizumab in adult patients with axial spondyloarthritis or psoriatic arthritis was evaluated in pooled results from integrated phase IIb/III clinical studies with a median exposure of 116 weeks. They reported most malignancies as singular events and no specific trends were observed [117]. They illustrated a reassuring safety profile, even at higher doses [117].

The brodalumab pharmacovigilance report, which included 7 years of data, found no new safety signal for malignancy with the crude rate of malignancy in 7 years of 1.01/100 patients which was less than in PSOLAR (1.78/100 patients) [118,119]. Similarly the data for ixekizumab is reassuring with observed malignancies in a pooled analysis of PSO and PSA data showing no increase incidence of cancer compared with the US population [120]. 5 year post marketing safety data for Secukinumab was also reassuring [121]. Longer term, prospective pharmacovigilance data is lacking for the newer IL-17 inhibitors and safety is inferred from other agents and trial data.

Overall rheumatology data for IL-17 inhibitors do not indicate increased malignancy risk, and current guideline positions reflect this reassuring evidence base [75,94].

3.1.9. Anti-IL-17 Antibodies in Gastroenterology

Anti-IL-17 antibodies are not used in gastroenterology as trials in CD showed clinical deterioration rather than improvement. Their blockade impairs mucosal barrier function and can enhance intestinal inflammation, making them unsuitable for IBD. For this reason, anti-IL-17 antibodies are generally avoided or contraindicated in patients with established IBD [122].

3.1.10. Ustekinumab in Dermatology

Ustekinumab targets the shared p40 subunit of both IL-12 and IL-23, both of which play an important role in carcinogenesis. IL-23 specifically, plays a vital role in gut tumorigenesis [123]. In dermatology literature, PSOLAR registry data has shown no increased risk of malignancy with ustekinumab for individuals prescribed treatment for less than or greater than 12 months [55].

The AAD/NPF guidelines state that ustekinumab may be used in patients with a prior solid-tumor malignancy who have not responded to other therapies [97]. A 2012 study of cumulative safety data from 4 studies, with patients with psoriasis exposed to ustekinumab for up to 3 years, found that rates of malignancies, excluding nonmelanomatous skin cancer, were not increased and were in line with rates in the general US population [124]. A recent study found ustekinumab showed a trend toward lower 5-year cancer risk compared with adalimumab, though this was not statistically significant without a 24-month lag [115].

Dermatology data therefore support a reassuring malignancy safety profile for ustekinumab, including use in selected patients with prior solid organ malignancy [55,97].

3.1.11. Ustekinumab in Rheumatology

Ustekinumab is used for psoriatic arthritis, systemic lupus erythematosus and giant cell arteritis [125]. There is a paucity of large, long-term ustekinumab studies focused exclusively on psoriatic arthritis, and registry data remain limited. A meta-analysis of 48 randomized trials in rheumatologic diseases reported that serious adverse events and malignancies were uncommon with anti–IL-23 therapies, including ustekinumab. While IL-12/23 p40 inhibitors showed slightly higher overall adverse event rates than IL-23 p19 agents, cancer incidence was not linked to IL-23 pathway blockade. Overall, ustekinumab and other IL-23 inhibitors demonstrated a favourable safety profile with no signal for increased malignancy risk [109]. The 3-year results from the PsABio real-world study of psoriatic arthritis noted 3/494 malignancies in the ustekinumab group and 4/557 in the anti-TNF group, when a lag time of 1 year was applied indicating a reassuring safety profile [126].

A study by Fiorentino et al. from the PSOLAR psoriasis registry found no increase in malignancy risk with ustekinumab in patients treated for over 12 months when compared to no ustekinumab treatment [55]. A 2019 study which integrated the 1 year safety data from 12 ustekinumab registrational trials included patients with moderate-severe psoriasis, psoriatic arthritis, or Crohn’s disease and found low and comparable incidences of nonmelanomatous or solid organ malignancies with placebo groups after 1 year of treatment [127]. Overall, ustekinumab has a reassuring safety profile for rheumatologic conditions though some data has been extrapolated from other inflammatory conditions.

Although rheumatology-specific registry data are smaller than for TNF inhibitors, available evidence does not indicate increased malignancy risk with Ustekinumab [55,109,126].

3.1.12. Ustekinumab in Gastroenterology

Ustekinumab is used to treat IBD. The 5 year follow-up data in CD from the IM-UNITI ustekinumab trial noted malignancy rates remained low, and concomitant therapies did not appear to affect ustekinumab’s safety or efficacy however, the sample size may be insufficient to identify rare events [128]. A 2023 meta-analysis of head-head cohort trials found that ustekinumab had a reassuring safety profile, particularly compared to TNF-inhibitors [129]. IBD data was aggregated in a meta-analysis of 18 randomised controlled trials and explored anti-IL-23 antibodies, including ustekinumab, in moderate-severe CD [130]. It observed a lower risk of adverse events than placebo but did not include malignancy or cancer incidence as a distinct endpoint or provide pooled data on malignancy risk [130].

A retrospective cohort study of 390 patients with IBD and a history of cancer found exposure to ustekinumab or vedolizumab does not appear to be associated with an increased risk of subsequent new or recurrent cancer [131]. Additionally, final pooled safety analysis of 2575 patients with IBD treated with ustekinumab, found malignancy events were not reported more frequently in ustekinumab treated patients [99]. Among IBD biologics, ustekinumab has one of the more reassuring datasets in patients with prior malignancy based on available retrospective cohort evidence [131].

3.1.13. Tocilizumab in Rheumatology

Tocilizumab is used to treat RA, giant cell arteritis and juvenile idiopathic arthritis. An evaluation of the tocilizumab therapy in human cancers describes the potential use of this anti-IL-6 antibody to supress IL-6 in tumour microenvironments, benefitting patients [132]. Current evidence indicates that tocilizumab is not associated with an increased malignancy risk in rheumatologic patients compared with DMARDs, TNF inhibitors, or other biologic therapies. Large cohort studies and meta-analyses consistently show reassuring hazard ratios for invasive solid and hematologic cancers (excluding nonmelanomatous skin cancer) [133,134]. However, higher risk groups such as nursing home residents, patients with pre-existing malignancies and rituximab users were excluded from that cohort study [134].

Integrated safety data from tocilizumab trials with a follow up of mean 2.4 years did not show and increased risk of malignancy [135]. A further meta-analysis has found no apparent increase in the rate of malignancy compared to controls [136]. Data for 1496 RA patients followed for a mean 32 months, from the French national registry ‘REGATE’ found no additional risk factors of cancer.

Overall available data support a neutral malignancy risk profile for tocilizumab in rheumatology, though dedicated prior-malignancy cohorts remain limited [133,134,135,136].

3.1.14. Anti-Integrin Medications in Gastroenterology

Anti-integrin therapies such as vedolizumab and natalizumab block leukocyte trafficking into inflamed tissue, thereby reducing immune-driven inflammation. Current evidence indicates that anti-integrin therapies, including vedolizumab and natalizumab, are not associated with an increased malignancy risk in gastrointestinal diseases such as Crohn’s disease [137]. Meta-analyses and systematic reviews of randomized trials and observational cohorts consistently show no elevation in overall cancer, lymphoma, or skin cancer compared with placebo or other biologics [137,138,139]. Pooled analyses likewise demonstrate no statistically significant increase in malignancy for either gut-selective agents (vedolizumab) or non–gut selective agents (natalizumab), with relative risks near 1 and broad confidence intervals [137,138].

Given their gut-selective mechanism, vedolizumab in particular is frequentlyconsidered in patients where malignancy risk is a major concern, and available data support a reassuring safety profile [107,131,140].

3.1.15. Anti-IL-4 and Anti-IL-13 Antibodies in Dermatology

Dupilumab and IL-13 pathway inhibitors have a generally reassuring malignancy safety profile in clinical trials, but observational studies raise specific concerns regarding cutaneous T-cell lymphoma (CTCL) and diagnostic unmasking. Dupilumab is a human monoclonal IgG4 antibody that inhibits IL-4 and IL-13 signalling by binding to the IL-4Rα subunit, thereby blocking the inflammatory pathways central to type 2 immune-mediated diseases [141]. Dupilumab is used to treat of moderate-to-severe atopic dermatitis in adults and children, as well as for prurigo nodularis and other type 2 inflammatory conditions [141,142].

Tralokinumab and lebrikizumab, both anti-IL-13 antibodies approved for moderate-to-severe atopic dermatitis in adults and adolescents [141]. The SOLO 1 and SOLO 2 studies for AD utilising dupilumab did not identify any signal for malignancy. The patient population was median age 36 and they were followed up for 16 weeks [143]. A 5 year open label extension study for patients diagnosed with AD did not find any association with malignancy [144]. Case series utilising dupilumab in patients with advanced solid organ cancer have indicated that AD can be safely controlled despite a malignancy diagnosis [145,146]. A pooled analysis of phase II and III placebo-controlled clinical trials of tralokinumab for moderate to severe AD did not show any increased risk of malignancy compared to placebo up to 52 weeks [147]. A 2020 systematic review of anti-IL-13 antibodies highlighted an excellent safety profile [148].

Several population-based studies, pharmacovigilance reports, and systematic reviews have suggested a possible association between dupilumab treatment for atopic dermatitis and an elevated risk of cutaneous T-cell lymphoma (CTCL). CTCL can present in a clinically similar way to AD and is associated with the newer treatments for AD and anti-IL-13 antibodies are implicated in exacerbating or negatively impacting the severity of CTCL [149]. In a large retrospective cohort analysis, dupilumab exposure was linked to a markedly higher likelihood of developing CTCL, with the majority of cases emerging more than a year after treatment initiation. No corresponding increase was observed for other types of cutaneous or lymphoid cancers [150]. These data support an association rather than proof of causation. Current evidence does not indicate that dupilumab or anti-IL-13 therapies exert a direct oncogenic effect, and the leading explanation is unmasking or acceleration of pre-existing malignant clones in patients misclassified as having AD or in whom early CTCL was not recognized [141,142]. Although data on anti-IL-13 agents such as tralokinumab remain limited, similar theoretical concerns exist due to their overlapping immunologic pathways.

Interestingly, the cytokine IL-13 is has a positive impact on survival in colorectal cancer [151]. However, elevated IL-13Rα2 (a cell surface receptor that binds IL-13 with high affinity) expression is frequently linked to tumour invasiveness, advanced disease stage, and metastatic potential, contributing to a poorer prognosis in malignancies such as glioblastoma, colorectal cancer and breast cancer [60,61,62]. Further research is needed to tease out the link between IL-13, CTCL and other malignancies.

3.1.16. Anti-IL-4/IL-13 Pathway Biologics in Respiratory Medicine

Anti- IL-4/Anti-IL-13 pathway biologics are utilised in respiratory medicine to treat severe asthma and, increasingly, COPD. In a large US cohort, dupilumab-treated patients demonstrated a higher incidence of lymphoma, particularly T/NK-cell lymphomas- compared with those on standard inhaled corticosteroid/long-acting β-agonist therapy. Despite this, overall cancer rates were unchanged, and all-cause mortality was lower among dupilumab users [152]. Randomized trials and meta-analyses in asthma and COPD populations have shown no increased risk of solid tumours or other hematologic cancers with dupilumab, and long-term data up to five years continue to support an overall favourable safety profile, aside from the observed lymphoma signal [152,153,154,155,156].

For tralokinumab and lebrikizumab, clinical trials and pooled analysis report no increased incidence of lymphoma or other malignancies, with no treatment-related cancers identified [157,158,159]. However, the trials included in the systematic reviews generally excluded patients with a prior malignancy, limiting conclusions in this subgroup [157]. Pre-clinical and clinical evidence reviewed by Braddock et al. found no evidence of elevated cancer risk associated with IL-13 pathway inhibition [160].

3.1.17. Anti-IL-5 and IL-5R Therapies—Respiratory

Anti-IL-5 biologics (mepolizumab and reslizumab) and the IL-5 receptor antagonist bendralizumab are widely used in severe eosinophilic asthma and have emerging roles in the management of COPD. Current evidence from randomized trials, meta-analyses, and post-marketing surveillance shows no increased malignancy risk associated with anti-IL-5 therapies s for these conditions [161,162]. Large systematic reviews, including a Cochrane analysis report no additional cancer risk compared with placebo, and long-term extension studies (up to 4.5 years) support a favourable and sustained safety profile [162,163]. A 5-year comparative safety analysis of benralizumab and mepolizumab noted small and similar numbers of malignancies across both studies [161].

Overall, respiratory data do not indicate increased malignancy risk with IL-5 pathway inhibition [161,162,163] and although current evidence is reassuring, in patients with a history of malignancy, treatment decisions should be individualised.

3.1.18. Omalizumab in Respiratory Medicine

Omalizumab, an anti-IgE monoclonal antibody, is established in the management of severe allergic asthma and chronic spontaneous urticaria. Early pooled clinical trial data reported malignancies in 0.5% of omalizumab-treated patients compared with 0.2% of control subjects [164], leading to inclusion of malignancy as a potential risk in the product label. However, subsequent pooled analysis in 2012 found no association between omalizumab treatment and malignancy risk, with a rate ratio below one implying that a causal link between omalizumab use and cancer development is unlikely [164].

Similarly, The EXCELS observational study, with a median follow-up of five years, found no significant difference in cancer incidence between omalizumab users and controls [165]. However, the follow-up duration was insufficient to account for cancers with a long latency period. Overall, omalizumab is considered safe with no malignancy signals in recent research [164,165].

3.1.19. Omalizumab in Dermatology

Long-term data show no evidence of increased malignancy risk in patients with chronic urticaria treated with omalizumab. Large real-world and multicentre cohort studies with follow-up periods of up to eight years confirm its favourable long-term safety, with no treatment discontinuations or malignancy signals reported [166,167]. Furthermore, meta-analyses and systematic reviews of clinical trials and observational studies consistently indicate that omalizumab is well tolerated, with malignancy not identified as a safety concern [168,169].

Recent comprehensive reviews across all approved indications likewise conclude that cancer risk remains comparable to background rates, and post-marketing surveillance has revealed no new safety issues [170]. Overall contemporary evidence supports a neutral malignancy risk profile for omalizumab across respiratory and dermatologic indications [164,165,166,167,169,170].

3.2. Current Guidelines

3.2.1. Dermatology

Regarding the dermatology guidelines, there are no cancer-specific recommendations provided or recommendations for particular biologics in the setting of malignancy. The AAD offers the most detailed discussion, stating that TNF inhibitors are not associated with an increased malignancy risk and can be used in patients with a previous cancer diagnosis. The guideline supports ustekinumab in this setting, advises that further evidence is needed for IL-17 inhibitors, and does not recommend IL-23 inhibitors for patients with a history of malignancy [97]. In contrast, the EADV takes a more permissive view, noting that TNF inhibitors, ustekinumab, and IL-17/23 inhibitors may be considered after consultation with oncology [56]. The BAD stresses individualized decision-making with multidisciplinary involvement but does not endorse or exclude specific biologic classes [171]. These differing positions underscore the complexity of managing psoriasis in patients with malignancy and highlight the need for clearer, more unified international guidance. (Table 4 and Table 5)

3.2.2. Gastroenterology

The ECCO, AGA, and ACG guidelines all provide structured, evidence-based assessments of malignancy risk associated with biologic therapy in inflammatory bowel disease [107,140,172]. ECCO offers the most detailed guidance, emphasizing differential malignancy risks across therapeutic classes—highlighting the established association between thiopurines and lymphoma and noting the absence of a clear cancer signal with newer agents such as vedolizumab and Ustekinumab [140]. The AGA similarly evaluates malignancy risk across biologics, concluding that anti-TNF agents carry a small but measurable lymphoma risk, whereas gut-selective and IL-12/23–targeted therapies have reassuring safety profiles [107]. The ACG guidelines reinforce these themes, underscoring the elevated cancer risk with thiopurines and the comparatively lower risk with targeted biologics, and advising individualized treatment in patients with current or prior malignancy [172]. Together, these guidelines consistently position vedolizumab and ustekinumab as preferred options when malignancy risk is a clinical concern (Table 4 and Table 5).

3.2.3. Rheumatology

The EULAR, ACR, and BSR guidelines all address malignancy considerations in the use of biologic agents [75,173,174]. The 2024 EULAR “Points to Consider” indicate that current evidence regarding the use of TNF inhibitors in patients with a prior history of malignancy is generally consistent and reassuring, demonstrating no significant increase in cancer recurrence compared with other therapeutic options. Nonetheless, EULAR advises that treatment decisions should be individualized, carefully considering the nature and timing of the previous cancer, the patient’s disease status, and made in collaboration with oncology specialists to ensure an informed and multidisciplinary approach to care [75]. They note particularly reassuring data for IL-17 and IL-12/23 inhibitors [75]. ACR similarly incorporates comparative malignancy evidence, noting no clear increased risk with newer non-TNF biologics [173]. BSR emphasises the favourable malignancy profile of IL-17 and IL-12/23 inhibitors [174]. Collectively, these guidelines support targeted non-TNF biologics when malignancy risk is a key clinical concern. Rituximab can also be used for RA when lymphoma risk is a concern (Table 4 and Table 5).

3.2.4. Respiratory Medicine

The 2026 Global Initiative for Asthma (GINA) [175,176], American Thoracic Society/European Respiratory Society (ATS/ERS) [177], and British Thoracic Society (BTS) [178] severe asthma guidelines provide detailed recommendations on the use of biologic therapies but do not explicitly address malignancy risk or provide guidance for patients with a cancer history. All three documents focus on efficacy, eligibility criteria, and general safety monitoring, without commenting on long-term oncologic outcomes. As a result, clinicians must rely on trial data and post-marketing evidence, rather than formal respiratory guidelines, when considering biologic therapy in patients with prior malignancy (Table 4 and Table 5).

4.0. Discussion

The interface between oncology and medical specialities prescribing biologic agents is clinically complex and requires a nuanced approach. The majority of conditions which are treated with biologic agents are chronic and mediated by immune dysregulation and chronic systemic inflammation [93]. Modern biologic treatments have radically improved outcomes for patients and have transformed our ability to treat safely and effectively though no treatment is without risk. Some patients may have been treated with historical therapies, like thiopurines, which have contributed to perceived elevated malignancy risk [179].

Some chronic inflammatory conditions may be associated with an increased risk of malignancy. For example, meta-analysis of 112 studies involving more than two million individuals with psoriasis or psoriatic arthritis reported a modest increase in overall cancer risk among patients with psoriasis, with a relative risk of 1.21 [54]. However, appropriate and effective disease control for inflammatory conditions improves the symptoms of the affected tissue, positively impacts systemic inflammation and contributes to overall health and general wellbeing [110,125,180,181,182].

This review has shown that reassuring data is emerging from pharmacovigilance registries and large prospective studies including many inflammatory conditions [55,119]. Evaluating true malignancy risk with new therapies is difficult as many malignancies have long latency periods and occur infrequently, even in the general population. Large patient numbers over prolonged periods are required to fully assess risk. Patients with a history of malignancy are often excluded from clinical trials with some exceptions [53]. Clinical trials often have relatively short follow-up periods and recruit only younger, generally well individuals and as such cannot account fully for malignancy risk. The global population is ageing and the variety of biologic therapies available is increasing. The number of patients with cancer-related comorbidities and those living beyond cancer treatment is steadily rising [183].

When oncologists and medical specialities are called to discuss malignancy risk with patients who require biologic medications, the discussion should be balanced, evidence-based and generally reassuring. Patients with a newly diagnosed malignancy of any type are understandably anxious and vulnerable to unnecessary avoidance of biologic therapies to treat their chronic disease. In the situation of an active or metastatic malignancy, particularly of an immunosensitive type, an individualised approach is required as the data regarding specific malignancies and named biologic drugs is limited to low quality data and case reports [184]. The impact on a patients quality of life from uncontrolled psoriasis, RA or IBD is significant. Drugs may need to be stopped temporarily in the event of a newly diagnosed malignancy but undertreating this group of inflammatory conditions because of a theoretical impacts on immunosurveillance and cancer risk is suboptimal.

The majority of data reported is reassuring for these targeted immune therapies and larger studies with longer follow-up times and of higher quality data support this. Where the question is safety in pre-existing malignancy, the most informative evidence is observational and registry-based, including cohorts that explicitly evaluate new or recurrent cancer following biologic exposure, such as BSRBR in rheumatology and IBD cohorts including patients with prior cancer [67,77,131]. Clinical trial data are generally supportive but usually not definitive for malignancy outcomes, except when trials include relevant prior-cancer subgroups or provide longer follow-up for malignancy events [53,99,103,185].

Guidelines for dermatology [56,97,171], rheumatology [173,174] and gastroenterology [65,172,186] recommend discussion with oncology colleagues in the setting of a newly diagnosed or historic malignancy. Inter-speciality collaboration, attention to emerging data and participation in large scale pharmacovigilance registries is essential to further our understanding of this complex area and to better treat our patients.

Across the conditions reviewed, the key limitation remains the relative absence of high-level evidence directly addressing recurrence risk in patients with prior malignancy. Where available, registry studies and retrospective cohorts provide the most clinically relevant signals, while randomised trials primarily inform short-term safety in selected populations. Case reports and case series can offer some additional evidence.

5.0. Conclusions

This review has described the safety profiles of many biologic agents with regards to malignancy risk and has examined cross speciality data. In general, biologic agents can be considered safer than older immune-suppressants or DMARDs. Many biologic agents are considered to minimally increase the risk of non-melanoma skin cancer including TNF-inhibitors, anti-IL-17 and anti-IL-23 agents.

When a patient with malignancy and a chronic immune mediated inflammatory disease requires systemic therapy, the following points are of relevance. Biologic agents such as TNF-inhibitors may be of concern for an active immune-sensitive cancer such as lymphoma, but reassurance for solid organ cancers can be drawn from rheumatology data and EULAR guidelines. When discussing individual agents with favourable safety profiles, newer biologics such as anti-IL-17 and -23 agents have less long-term data however their preclinical studies and pharmacovigilance data is particularly reassuring. Anti-IL-23 agents have shown positive safety signals when trialed in those with a history of malignancy, although the numbers were small. There is a concern regarding dupilumab and the potential ‘unmasking’ or association with CTCL and further exploration is warranted. There is a clear need for validated decision frameworks that incorporate cancer type, stage, prior therapies, and latency, alongside the clinical impact of chronic immune mediated diseases.

The number of younger patient (less than 50 years old) diagnosed with new malignancy is increasing globally so the number of patients prescribed these agents in the setting of cancer will undoubtedly increase [187]. We recommend mandatory engagement with real world registries and databases as a condition of approval for new biologic agents which could be done with a pragmatic monitoring approach. Post marketing surveillance provides the most clinically relevant information regarding true malignancy risks. Appropriately treating the complex clinical situation of patients with inflammatory and immune mediated disease with a concomitant diagnosis of malignancy is an essential focus of future research and clinical guidelines.