Therapies with hydrocortisone enemas or foam are effective for inducing remission [2, 10, 14, 15]. Suppository foam reaches approximately 15–20 cm from the anal verge and enemas often as far as the splenic flexure [2, 3, 16–22]. They have not been shown to be effective in maintaining remission [3]. Due to difficulty retaining liquid enemas, particularly at times when the patient is in an acute flair, 10 % hydrocortisone foam is well recognized to be often better tolerated. The author’s general approach has been to use hydrocortisone foam for 2 weeks nightly and then attempt converting to either oral, topical, or dual mesalamine. Depending on the severity of patient’s symptoms and time of remission, the foam can be alternated nightly with mesalamine for a short period of time also. Patient’s refractory to this should use a combination of oral and topical mesalamine therapy. Other formulations beside hydrocortisone include Prednisolone 21-phosphate and beclomethasone dipropionate. These are both available as suppositories and enemas although are less commonly available in the USA.

Budesonide is a steroid which undergoes rapid first pass hepatic metabolism resulting in less systemic absorption of the medication. It is used orally for the treatment of right-sided colonic and ileal disease for patients with Crohn’s disease. It is available in enema form. The recommended dose of 2 mg is not available yet in the United States but seems to be as effective as hydrocortisone with less systemic side effects [2, 16, 17]. Recently, oral Budesonide MMX gained regulatory approval for ulcerative colitis.

Rarely, systemic corticosteroids are required for the treatment of UP. This should be reserved for patients who are failing maximal topical therapy as well as maximum dose oral mesalamine. Inflamed rectal mucosa shows relatively poor absorption of oral steroid formulations. Given this fact and the well-known high rate of systemic side effects, oral corticosteroids are generally a temporizing measure to a more definitive therapy with either an immunomodulator or biologic agent.

Azathioprine (AZA) and 6-mercaptopurine (6-MP) are immunomodulator medications used in the treatment of both Crohn’s disease and ulcerative colitis. Small studies have shown benefit of 6-MP for ulcerative proctosigmoiditis. Love et al. [23] reported improvement in 63 % of patients with steroid refractory disease while on doses of 25–150 mg/day. About 1/3 of these patients developed a relapse while on 6-MP, but remission was restored in 88 % with a short course of steroids and continued 6-MP use. Their primary role in ulcerative colitis and ulcerative proctitis is as steroid-sparing agents rather than as primary therapy to induce remission. It needs to be emphasized that no specific studies have shown a beneficial effect of 6-MP in the use of ulcerative proctitis (as opposed to the studies noted above looking at ulcerative proctosigmoiditis).

Methotrexate is often used to induce remission in patients with Crohn’s disease or Crohn’s colitis, but no controlled data supports the use of methotrexate in patients with ulcerative colitis.

Infliximab is a chimeric anti-TNF-alpha antibody that has been demonstrated in large randomized placebo-controlled trials to be effective for the treatment of moderate to severe ulcerative colitis [24]. More recently, a fully human monoclonal antibody that binds TNF-alpha, Adalimumab, has been approved for induction and maintenance of remission in patients with moderate to severe ulcerative colitis. Infliximab has not been evaluated in large studies on ulcerative proctitis patients: however, several small studies have shown efficacy. Out of 13 patients treated with infliximab at 5 mg/kg for refractory ulcerative proctitis at 6 referral centers between 2005 and 2009, 9/13 (69 %) had a complete response, 2/13 (15 %) had a partial response, and 2/13 (15 %) were primary nonresponders [25, 26]. This suggests a role for infliximab for patient’s refractory to other agents. Adalimumab has not been studied specifically for ulcerative proctitis. Case reports have described the use of topically administered infliximab for patient’s refractory to systemic therapy, but no controlled studies have been performed [27].

Recent studies have looked at the use of oral tacrolimus for treatment of ulcerative colitis (although not specifically in ulcerative proctitis) [28]. Tacrolimus is a potent immunosuppressant in the FK506 family of agents often used for immunosuppression in the setting of organ transplant. Oral tacrolimus is associated with numerous side effects including hypertension, hematologic abnormalities, renal impairment, and increase in skin cancers. Topical tacrolimus is effective in numerous inflammatory conditions, and several studies have showed efficacy in ulcerative proctitis resistant to other therapies. In one study, 19 patients with ulcerative proctitis were treated for 4 weeks with a daily 2–4 mg enema or a 2 mg suppository [29]. 13/19 patients showed clinical and histologic improvement of disease activity after 4 weeks of treatment. More importantly, blood trough levels were followed and were too low to induce systemic immune suppression, and patients had minimal side effects. Cyclosporine has a similar mechanism of action to tacrolimus but is not available topically and has not specifically been studied for ulcerative proctitis.

Several experimental therapies have been tried for ulcerative proctitis although none have been approved by the FDA. In a case report, granulocyte, macrophage, and monocyte apheresis was effective, and the patient was able to be bridged to azathioprine [29]. Antibiotics have shown poor efficacy in the treatment of ulcerative colitis generally. Nicotine enemas [30, 31] have not proven effective. Limited data on the use of short-chain fatty acid enemas in combination with oral 5-ASA agents [32] have shown modest benefits but are not readily available. A small prospective study showed a modestly good effect in the use of arsenic suppositories 250 mg twice daily for 4 weeks with minimal side effects [33]. Probiotics are an area of active interest for ulcerative colitis although no studies have shown beneficial effects.

Recently regulatory approval for vedolizumab was introduced in the United States for refractory ulcerative colitis and Crohn’s disease. Though this agent has not been formally assessed in patients with ulcerative colitis limited to proctitis, the perception is that this agent is effective in patients with all disease distributions.