In the 1950s, British doctors Truelove and Witts introduced corticosteroids for the treatment of ulcerative colitis, turning a disease occasionally associated with death into a chronic condition.
However, corticosteroids are associated with many side effects, including increased risk of infections, osteoporosis, increased risk of diabetes and hypertension, cataracts, mood changes, and difficulty sleeping (insomnia), to name a few. Therefore, steroids are not advised to be used except for short-term treatment of flares.
The past decades, however, have seen a significant advance in the treatment of ulcerative colitis with more drugs available to patients. Unfortunately, none of them are entirely free of risks and side effects.
Mesalazine for Ulcerative Colitis
5ASA (mesalamine, mesalazine) are anti-inflammatory medications widely used for mild conditions. Since they are not immune-suppressing drugs, their safety profile is overall very good, and there is no increased risk of infections with these medications.
However, in 1% of patients, they may cause diarrhea, sometimes accompanied by fever, which can be difficult to distinguish from an exacerbation of the underlying colitis for which they were prescribed.
Other more rare side effects include pancreatitis, hypersensitivity allergic reactions, and a specific type of kidney immune inflammation (interstitial nephritis), requiring follow-up urine and kidney function tests every 6-12 months in patients on regular treatment.
Immunosuppressants for Ulcerative Colitis
Other drugs used for UC are mostly immunosuppressants, which reduce the activity of the immune system. As such, they are generally all linked to some increase in the risk of infections, although this is usually a small added risk.
Side Effects of Immuran & Purinethol for Ulcerative Colitis
Azathioprine (Immuran) and 6mercaptopurine (Purinethol) are long-known oral agents, shown to increase the risk of some viral infections, including a severe form of EBV (mononucleosis) infection. They are also linked to an increased risk of lymphoma (cancer of lymph nodes) and some forms of skin cancer.
Immuran and Purinethol are also associated with a risk for bone marrow suppression (reduction in the number of immune white blood cells), inflammation of the liver (hepatitis), and pancreatitis. These risks are infrequent, but still need to be recognized. It’s recommended to seek advice and information from your doctor regarding these risks.
Side Effects of Biologic Medication for Ulcerative Colitis
Among the biologics, are the anti-TNF agents, including Infliximab (Remicade and its biosimilars), adalimumab (Humira and its biosimilars), and golimumab (Simponi). These are all associated with an increased risk of infections as well as a slight excess risk for melanoma skin cancer. These agents should be avoided in patients with severe heart failure, as they may worsen the condition.
Other biologic drugs such as Vedolizumab (Entyvio) and ustekinumab (Stelara) seem to have better safety profiles and are not linked to increased infection rates to date.
The Latest Medical Treatment for Ulcerative Colitis
There is less clinical experience with more recently approved oral drugs in the U.S and Europe, including tofacitinib (Xeljanz), Ozanimod (Zeposia), upadacitinib (Rinvoq), and Filgotinib (Jyseleca).
However, both Tofacitinib, Upadacitinib, and Filgotinib may be associated with an increased risk of some infections, in particular varicella zoster (shingles), so zoster immunization is advocated before their use.
A slightly increased risk with some cancer types has also been reported, although the risk is very small, and all three are also linked to possible suppression of blood counts and increases in cholesterol levels, so they require monitoring blood tests for these possible changes.
Most importantly, perhaps, tofacitinib (Xeljanz) received a warning label by the FDA for the potential increased risk of causing venous thrombosis. This potentially life-threatening side-effect has been reported in tofacitinib-treated patients with rheumatoid arthritis who were over the age of 50 and at risk for cardiovascular diseases. It has not been reported to date in UC patients.
However, the warning by the FDA remains for all patients and was extended to these three drugs with a similar mechanism of action, so all three (Xeljanz, Rinvoq, and Jyseleca) may need to be avoided in patients with other risk factors for thrombosis (family or personal history of thrombosis, smokers, post-surgery, etc.).
Finally, Ozanimod (Zeposia) is a new class of drug, used originally in multiple sclerosis. The side effects reported include blood cell reduction, heart rate changes, and some eye retinal derangements. Consulting with your doctor about these risks is prudent before starting Ozanimod.
Know Your Options
In summary, while there has been tremendous progress in the field of UC treatment, with multiple new drugs being available, unfortunately, none are completely free of possible side effects. Knowing these potential side effects is important for your discussion with your doctor about the pros and cons of drugs that may improve or control your UC condition.
Shomron Ben-Horin
