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Patients with psoriatic arthritis (PsA) were at increased risks for malignancy, and possibly more so if they were treated with conventional disease-modifying antirheumatic drugs (DMARDs), a meta-analysis found.
In nine cohort studies that included more than 43,000 PsA patients, the pooled relative risk for overall malignancy was 1.29 (95% CI 1.04-1.60) compared with the general population, according to Yunyun Fei, MD, and colleagues from Peking Union Medical College in Beijing.
And for patients who were using conventional DMARDs, the pooled relative risk was 1.75 (95% CI 1.40-2.18), the researchers reported in Seminars in Arthritis & Rheumatism.
Clinical efficacy has been clearly demonstrated for various DMARDs and biologics, but it's not yet clear if there are long-term risks for rare adverse events such as cancer with these treatments. Some studies have found increased risks of malignancies such as breast cancer, while other reports found no increases among patients with PsA.
Because of the underlying immune system abnormalities and immunosuppressive effects of medications used for PsA, the researchers sought to analyze the available data to provide an up-to-date estimate of cancer risks. The team therefore undertook a systematic literature review and meta-analysis of studies published through March 2018 that included at least 20 patients, had sufficient duration of follow-up, and provided adequate detail on treatment regimens.
Unlike for patients treated with conventional DMARDs, no risks were seen for overall malignancy among those receiving biologic therapies, with a pooled relative risk of 0.957 (95% CI 0.80-1.14).
The meta-analysis also identified an elevated risk for nonmelanoma skin cancer, with a pooled relative risk of 2.46 (95% CI 1.84-3.28), but not for other specific cancers:
- Urinary tract cancers, RR 1.07 (95% CI 0.90-1.27)
- Digestive tract cancers, RR 0.82 (95% CI 0.62-1.09)
- Lymphoid/hematopoietic and related malignancies, RR 1.17 (95% CI 0.93-1.46)
- Breast cancer, RR 0.98 (95% CI 0.85-1.14)
- Respiratory tract cancers, RR 1 (95% CI 0.73-1.36)
The authors noted that there was a high degree of heterogeneity among the studies (I2 =71.37%), but no publication bias was evident.
The observation in this meta-analysis that treatment with biologics was not associated with an increased risk of malignancy concurs with what was seen in the Safety Assessment of Biological Therapeutics study, which included almost 30,000 patients with rheumatoid arthritis, PsA, psoriasis, and inflammatory bowel disease treated with tumor necrosis factor (TNF) inhibitors. In that study, no significant increased risk was seen for any of the 10 most common cancers among anti-TNF-treated patients compared with patients treated with other therapies.
As to why conventional DMARD treatment might be associated with increased risk, the authors of the meta-analysis pointed to anti-metabolite properties and decreased anti-cancer surveillance by the immune system with drugs such as methotrexate as possibly playing a role. However, the team noted that studies considering this concern had small numbers of patients and lacked adequate controls, "leaving it open to interpretation whether cancer risk is associated with the therapeutic agent or with the disease itself. No clear conclusion can be drawn regarding whether conventional DMARD use may increase cancer risk."
With regard to the risk of nonmelanoma skin cancer, the authors noted that risks with immunosuppressive medications have been demonstrated in the transplant literature, and a large North American registry of patients with PsA found an incidence rate of 0.21 per 100 patient-years for nonmelanoma skin cancer. "It seems that more attention should be paid to monitoring nonmelanoma skin cancer during PsA treatment," Fei and colleagues cautioned.
However, they also pointed out that none of the studies included in their meta-analysis reported on the use of high-dose psoralen and ultraviolet A radiation treatments for psoriasis, which could influence skin cancer risks.
"Large-scale longitudinal studies will be essential for drawing firm conclusions regarding PsA-associated risk for malignancy, including the effects of treatment and the identification of disease- and person-specific risk factors."
A limitation of the study, the researchers said, was the inadequate detail in some studies about specific cancer diagnoses.
The study was funded by the National Natural Science Foundation of China and the Chinese Academy of Medical Sciences Initiative for Innovative Medicine.