- Indian Rheumatology association
It’s a Himalayan challenge for a clinician to assess the cancer risk of patients on DMARDs in India as the disease per se and the varied treatment regimens (monotherapy, combination therapy, use of OTC medications, exposure to CAM etc.) dually contribute to increased malignancy risk. DMARDs decrease tumor surveillance complicating risk assessment. Due to data from different populations and several confounding factors studies on malignancy risk show disparate results to draw strong conclusions. Risk factors for malignancy in RA are male sex, increasing age, first 5 years following diagnosis, Felty’s syndrome. Smoking related cancers in men and hematological cancers are more incident in rheumatoid arthritis patients than the general population.
Several trials reveal a positive role for NSAIDs in chemoprevention and treatment in solid tumors and hematological malignancies especially when used at higher doses for a longer duration but genetic variations in NSAID-related genes lead to varied responses and high cardiovascular risk negates any potential benefit NSAIDs may have in chemoprevention. Long-term steroid therapy suppresses innate immunity, decrease in B-cell counts and tumoricidal activities of macrophages. Long-term exposure might be associated with a higher overall cancer risk especially for lung and liver cancer. However steroid therapy use less than two years is not associated with lymphoma risk in a Sweden cohort study.
Hydroxychloroquine and sulfasalazine are not associated with increased risk of cancer. The risk of B cell lymphoma may be increased with Methotrexate and Azathioprine. One study showed that Leflunomide is associated with threefold increased risk of pancreatic cancer. Mycophenolate mofetil is associated with possible risk of CNS lymphoma. Cyclophosphamide (Oral >> IV) is associated with increased risk of malignancies like bladder cancer, lung cancer, leukemia etc. Bladder cancer was observed in 25% of patients receiving a cumulative dose of 80 g cyclophosphamide. Hydration and mesna help in reducing this risk.
There is no increased overall risk associated with biologics use. Patients who develop a solid organ malignancy on bDMARDs do not appear to have a worse histology, extensive disease or worse prognosis. Patients with prior solid organ malignancy are not likely to get recurrence when on bDMARDs if in remission for at least 5 years after starting bDMARD. Anti TNF are associated with increased risk of non-melanoma skin cancer and possibly melanoma especially in males and Caucasians. Skin surveillance should be encouraged in at risk patients especially those on higher doses or longer exposure. There is no difference in individual TNF inhibitors in terms of malignancy risk. Rituximab is effective in the treatment of B-cell lymphomas in patients with RA. Data regarding Tocilizumab and Abatacept is not robust to draw any conclusions.
