When your ulcerative colitis is active, symptoms can vary from mild to severe, depending on:

​

1) the extent of disease (i.e. how much of the colon is affected by inflammation), and

2) the severity of inflammation.

​

Both factors determine the appropriate treatment in the acute phase.

​

The Aim: Getting into Clinical Remission

The drugs listed below are used to cause your active disease to go into clinical remission (absence of UC symptoms), endoscopic remission (no visible evidence of inflammation in the colon during a colonoscopy) or ideally histologic/deep remission (complete healing of colonic mucosa as seen under microscope, here). The author has ranked these drugs by the order in which they are generally given, though ultimately these decisions come down to individual doctors (see here for NICE guidelines).

​

1. Mesalazine (brand names include Pentasa, Lialda, Asacol, Octasa, Zintasa and others; sometimes spelled mesalamine)

2. Budesonide MMX (this is a specific formulation of the steroid budesonide, designed to act only on the colon and is viewed as being much gentler than prednisolone, but efficacy is limited (here))

3. Prednisolone (Predfoam for enema, generic prednisolone for tablets; also known as prednisone, which your body converts into prednisolone upon ingestion)

4. Anti-TNF biologic (Remicade/infliximab, Humira/adalimumab, Simponi/golimumab - these are three separate drugs but all work in a similar way; there are also biosimilars for these which use other brand names)

5. Entyvio (vedolizumab)

6. Stelara (ustekinumab)

7. JAK inhibitors (Xeljanz/tofacitinib, Rinvoq/upadacitinib)

​

The above list is meant to be a rough guide only. Depending on the individual circumstances of the patient, some treatments will likely be skipped completely or tried in a different order or in combinations with each other. The formulations will also vary, depending on the extent of disease (suppositories for proctitis, enemas for procto-sigmoiditis, pills or IV infusions for left-sided colitis or pancolitis). Below, we explore each option in a little more detail. Note that the anti-TNFs, Entyvio and Stelara are known as "biologics" as they are manufactured using living organisms (bacteria, usually). Due to the large molecular size of biologics, they are often administered intravenously (i.e. in a drip). 

​

Mesalazine

Mesalazine is effective at dealing with mild ulcerative colitis, inducing remission in 30-40% of patients (here). Due to its very benign safety profile, it is usually taken alongside other treatments if remission is not achieved on it alone. The formulation may be as oral pills, enemas or suppositories and the dose also varies, with 4.8g/day used for induction of remission and 2.4g/day for maintenance of remission.

​

Budesonide MMX

Budesonide, like prednisolone, is a corticosteroid, but the budesonide MMX formulation is a pill that wraps the active ingredient in a covering that prevents release of the drug until it reaches the colon. The idea behind this is that it reduces the known side effects associated with corticosteroid use (e.g. systemic immune suppression) as it only acts locally in the colon. However, studies show that its efficacy is fairly limited, with 15% of patients achieving remission vs 7% in the placebo arm (here). Budesonide MMX is therefore often not used in sicker patients.

​

Prednisolone

When oral prednisolone was introduced, it revolutionised UC treatment. It generally achieves remission in 70-80% of cases (here), can lead to improvement in just 1-4 days and is especially effective in milder disease. If disease is limited to within about 20cm of the rectum, then prednisolone enemas can be used (brand name is Predfoam), which retains the same efficacy but significantly reduces the systemic side effects, meaning it can be used more often. A normal prednisolone course taken orally tapers from 40mg/day down to 0mg over 8 weeks and typically is not used more than twice a year due to the adverse side effect profile. These side effects typically worsen over time and include infections, ulcers, osteoporosis, atherosclerosis, weight gain, "moon face", insomnia, eye problems and thinning of hair and skin. Unfortunately, many of these side effects are common and become increasingly likely the longer the drug is taken. Prednisolone is therefore only used to induce remission, not to maintain remission. It tends to lose effectiveness over time; a patient who relapses soon after discontinuing prednisolone is known as "steroid-dependent", and one who does not respond to it at all is known as "steroid-refractory". 

​

Anti-TNFs

For patients who are steroid-refractory or steroid-dependent, the TNF drugs are a good option, with Remicade/infliximab the most popular, which may be infused or subcutaneously injected depending on the formulation. Sometimes, azathioprine is prescribed before them, but its use is more in the maintenance setting than the acute setting. For a patient with active disease, the TNF drugs have a good (~70%) initial induction of remission rate (here), but unfortunately this high level of response rapidly wanes and after 1 year, only around 20-25% of patients remain in clinical remission on TNFs alone. This remission rate can be doubled by adding azathioprine (here) to around 40% long-term remission, but that combination causes a high level of immune suppression and has been known to cause a very rare and aggressive cancer called hepatosplenic T-cell lymphoma (here) in young males. Due to the extreme rarity of this side effect, it is generally believed that the benefits of the combination outweigh the risks (here). 

​

Entyvio

This intravenously-administered drug is an integrin inhibitor that is infused every 8 weeks and has generally been viewed as a last-line option along with Stelara for those who have failed on all alternatives (before the JAKs were approved). Efficacy is modest, with 17% achieving clinical remission at week 6 and 42% of these maintaining this at 52 weeks (here). It tends to be used on very hard-to-treat patients (along with Stelara and the JAK inhibitors).

​

Stelara

This is another biologic (infused intravenously for the loading dose, followed by subcutaneous injections every 8 weeks) but is an anti-interleukin (IL-12 and IL-23). It plays a similar role to Entyvio in that it is a last line option for patients who have failed on TNFs, but it works in a different way. The strength of the clinical data is also similar (here), with 19% clinical remission rates at week 8 (vs 7% for placebo) and like Entyvio, the safety is generally acknowledged as being better than the JAKs.

​

JAK inhibitors

Xeljanz (tofacitinib) and Rinvoq (upadacitinib) are both JAK inhibitors and work in similar ways. Remission rates are again modest, with Xeljanz recording (here) 17% at week 8 (vs 4% placebo) and Rinvoq recording (here) 26-33% at week 8 (vs 4-5% placebo). Unfortunately, side effects are an issue, with serious infections and malignancies occurring with both drugs and Rinvoq also causing higher rates of cardiovascular death and thrombosis. For this reason, it is not recommended to combine with other immune-suppressants such as the TNFs, Stelara, Entyvio, azathioprine or corticosteroids.

​

Pipeline treatments

The treatment of active ulcerative colitis is a busy area on ongoing research. A drug called Zeposia (ozanimod) was recently approved (May 2021 in the US) for this setting (here) and demonstrated 18% clinical remission rates at week 10 (vs 6% for placebo). This is another option that patients now have, with a similar level of efficacy to Entyvio, Stelara and the JAKs, but still some way behind the TNFs.

​

There are many other treatments undergoing clinical trials, but it goes beyond the scope of this website to fully examine these drug candidates.

​

A Note on Treatment for Anaemia During Active Disease

Anaemia commonly occurs in active disease given the volume of blood loss (here). Such patients are commonly prescribed oral iron, but ECCO guidelines now recommend IV iron for active UC patients with severe anaemia (here), as oral iron supplements are associated increased severity of colitis (here). However, IV iron is often difficult to get access to given it must be administered in a hospital setting, so other alternatives include, 1) eating more iron-rich food (e.g. red meat, liver, beans), though obviously this can be very challenging in a flare, and 2) taking Accrufer (also known as Feraccru or ferric maltol) capsules, which are still oral iron but differently formulated so that the risk of UC worsening may be reduced (here). It is very important to note that this drug is not recommended for UC patients with active disease, but if the only alternative is generic oral iron, it may still be preferable. The only other option is to not treat anaemia, which the author does not recommend, as it tends to grow in severity until hospitalisation is required (at which point blood transfusions and/or IV iron may be necessary).