FDA approves Boxed Warning about increased risk of thrombosis with higher dose of tofacitinib used for ulcerative colitis

Dr KK Aggarwal

(Excerpts from US FDA): In an update to its Drug Safety Communication issued on February 25, the US FDA has approved new warnings about an increased risk of thrombosis (blood clots) and of death with the 10 mg twice daily dose of tofacitinib, which is used in patients with ulcerative colitis. Tofacitinib 10 mg twice daily is not approved or recommended for the treatment of rheumatoid arthritis or psoriatic arthritis.

The FDA has issued the following safety information:

• For the treatment of ulcerative colitis, reserve tofacitinib as second-line therapy for use in patients who have failed or cannot tolerate TNF blockers.
• For ulcerative colitis, use tofacitinib at the lowest effective dose and for the shortest duration needed to achieve/maintain therapeutic response.
• The induction dose is 10 mg twice daily for 8 weeks. Evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed, continue 10 mg twice daily for an additional 8 weeks or a maximum of 16 weeks. Discontinue 10 mg twice daily after 16 weeks if adequate therapeutic response is not achieved.
• The maintenance dose is 5 mg twice daily. Use of 10 mg twice daily beyond induction should be limited to those with loss of response and used for the shortest duration, with careful consideration of the benefits and risks for the individual patient. Use the lowest effective dose needed to maintain response.
• Discontinue tofacitinib and promptly evaluate patients with symptoms of thrombosis.
• Avoid tofacitinib in patients who may be at increased risk of thrombosis.
• Counsel patients to seek medical attention immediately if they experience unusual symptoms, including those of thrombosis.

·                     Encourage patients to read the Medication Guide they receive with each tofacitinib prescription, which explains the safety risks and provides other important information.

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

Aim to achieve mucosal healing when treating patients with ulcerative colitis

The American College of Gastroenterology has updated its guidelines on diagnosis and management of ulcerative colitis in adults. These guidelines have been published in the March 2019 issue of the American Journal of Gastroenterology

Some key recommendations include:

·         Do a stool test to exclude clostridium difficile infection in patients suspected of having ulcerative colitis.

·         Serologic antibody testing is not recommended to either establish a diagnosis or determining the prognosis.

·         Treatment should aim to achieve mucosal healing to increase the chances of sustained steroid-free remission and prevent hospitalizations and surgery. Mucosal healing is defined as resolution of inflammatory changes (Mayo endoscopic subscore 0 or 1).

·         Fecal calprotectin can be used as a noninvasive marker of disease activity and to assess response to therapy and relapse.

·         Preferably use rectal 5-aminosalicylate enemas (at least 1 g/d) over rectal steroids for induction of remission in mildly active left-sided UC.

·         Oral budesonide multi-matrix (MMX) 9 mg/d is recommended for induction of remission in patients with mildly active left-sided UC who are intolerant or nonresponsive to oral and rectal 5-ASA.

·         In patients with moderately to severely active UC of any extent, oral systemic corticosteroids are recommended to induce remission.

·         Monotherapy with thiopurines or methotrexate are not recommended for patients with moderately to severely active ulcerative colitis. Instead, anti-TNF therapy (adalimumab, golimumab or infliximab) should be used in these patients for induction of remission.

·         Do not use systemic corticosteroids for maintenance of remission in these patients.

·         In patients with acute severe ulcerative colitis, DVT prophylaxis and testing for C. difficile infection are recommended. Avoid routine use of broad-spectrum antibiotics in these patients.

·         Consider colectomy in patients with moderately to severely active UC who are refractory or intolerant to medical therapy.

(Source: Am J Gastroenterol. 2019 March;114(3):384-413).

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

Use mesalamin in standard dose rather than low dose in patients with extensive mild-to-moderate ulcerative colitis

The American Gastroenterological Association (AGA) has published a new clinical guideline for the medical management of patients with mild-to-moderate ulcerative colitis (UC).

According to the guideline, mild-to-moderate UC is characterized by mild or moderate rectal bleeding, <4-6 bowel movements in a day, absence of constitutional symptoms, low overall inflammatory burden, and absence of features suggestive of high inflammatory activity. However, the guideline also cautions that those who have more frequent bowel movements, more prominent rectal bleeding or greater overall inflammatory burden should be considered to have moderate disease.

Key recommendations include:

·         In patients who have extensive mild-moderate disease, use of either standard dose mesalamine (2-3 g/day) or diazo-bonded 5-aminosalicylic acid (5-ASA) is recommended instead of low dose mesalamine, sulfasalazine or no treatment (Strong recommendation, moderate quality evidence).

·         Add rectal mesalamine to oral 5-ASA in patients with extensive or left-sided disease (Conditional recommendation, moderate quality evidence).

·         In patients with mild–moderate UC with suboptimal response to standard-dose mesalamine or diazo-bonded 5-ASA or with moderate disease activity, use high-dose mesalamine (>3 g/d) with rectal mesalamine. (Conditional recommendation, moderate-quality evidence [induction of remission], low-quality evidence [maintenance of remission])

·         Oral mesalamine should be administered once-daily rather than multiple times during the day (Conditional recommendation, moderate quality evidence).

·         Standard-dose oral mesalamine or diazo-bonded 5-ASA is recommended, rather than budesonide MMX or controlled ileal-release budesonide for induction of remission (Conditional recommendation, low quality of evidence).

·         In mild–moderate ulcerative proctosigmoiditis or proctitis, use of mesalamine enemas (or suppositories) rather than oral mesalamine is recommended (Conditional recommendation, very-low-quality evidence).

·         For patients with mild–moderate ulcerative proctosigmoiditis who opt for rectal therapy over oral therapy, use mesalamine enemas rather than rectal corticosteroids (Conditional recommendation, moderate-quality evidence).

·         Mesalamine suppositories are recommended for patients with mild–moderate ulcerative proctitis who prefer rectal therapy over oral therapy (Strong recommendation, moderate-quality evidence).

·         In cases of mild to moderate ulcerative proctosigmoiditis or proctitis being treated with rectal therapy who are intolerant of or refractory to mesalamine suppositories, use rectal corticosteroid therapy rather than no therapy for induction of remission (Conditional recommendation, low-quality evidence).

·         Add either oral prednisone or budesonide MMX in patients with mild–moderate disease, which is refractory to optimized oral and rectal 5-ASA, regardless of disease extent (Conditional recommendation, low-quality evidence).

The guideline makes no recommendations for the use of probiotics or curcumin in these patients (No recommendation, knowledge gap). It also says that fecal microbiota transplantation should be performed only in the context of a clinical trial in patients with mild to moderate disease without Clostridium difficile infection (No recommendation for treatment of ulcerative colitis, knowledge gap).

(Source: American Gastroenterological Association Press Release, Jan. 10, 2019)

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

Emedinews: Breaking News: Infliximab for Children with Ulcerative Colitis

An US FDA advisory panel has recommended infliximab to include in the treatment of ulcerative colitis in children.