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POOLED ANALYSIS OF LONG-TERM MMX®,* MESALAMINE SAFETY
D Solomon1, K Paridaens2, M Palmen3, K Barrett3, P Streck11Shire Development Inc, Wayne, PA, US; 2Shire AG, Eysins, Switzerland; 3Shire Pharmaceuticals Inc, Basingstoke, United Kingdom
Aims: Ulcerative colitis (UC) is a chronic inflammatory disease with relapsing-remitting symptoms that often affect patients for their entire lives. As UC patients may require lifelong treatment, the long-term safety of UC therapy is very important. To evaluate the long-term safety of MMX mesalamine in the treatment of UC, safety data from three clinical trials were pooled and analyzed.
Methods: In a phase 3 trial, patients in clinical and endoscopic remission (modified UC Disease Activity Index score =<1, rectal bleeding and stool frequency scores of 0, no mucosal friability, and a >=1-point reduction from baseline in sigmoidoscopy score) were randomized to 2.4 g/day MMX mesalamine administered either once daily (QD) or as 1.2 g twice daily (BID) for 12 months. In a second phase 3 trial, patients in endoscopic remission (endoscopy score =<1 and a combined symptom score =<1 for stool frequency and rectal bleeding) were randomized to either 2.4 g MMX mesalamine QD plus placebo BID, or 0.8 g delayed-release mesalamine BID (1.6 g/day total) plus placebo QD for six months. In a phase 4 trial, patients with quiescent UC (no rectal bleeding and 0-1 bowel movements/day more than normal) received 2.4 g MMX mesalamine QD for 12 months.
Results: In total, 1,083 patients were enrolled or randomized to MMX mesalamine treatment across the three studies. Of these, 1,082 received >=1 dose of MMX mesalamine for a mean treatment duration of 40.7 weeks. Among patients who received >=1 dose of MMX mesalamine, 451 (41.7%) reported >=1 adverse events (AEs) with 237 (21.9%) experiencing only mild AEs, 176 (16.3%) experiencing AEs with a maximum severity of moderate, and 38 (3.5%) experiencing severe AEs. Serious AEs were reported by 33 (3.0%) patients and 122 (11.3%) patients experienced AEs that were possibly related to study treatment. A total of 43 (4.0%) patients experienced AEs that led to withdrawal from their respective studies. The most frequently reported AEs (excluding UC) were headache (2.9%) and nasopharyngitis (2.8%). Among treatment-related AEs, the most common (excluding UC) were abdominal pain, abdominal distension, upper abdominal pain, diarrhea, dyspepsia and increased alanine aminotransferase (0.6% to 0.9%). Overall, the majority (58.3%) of patients who received MMX mesalamine did not experience any AEs and >90% of patients who reported AEs experienced ones that were mild to moderate in severity. The majority of reported AEs were considered to be unrelated to MMX mesalamine treatment.
Conclusions: These findings indicate that long-term treatment of UC patients with MMX mesalamine is generally safe and well tolerated.
*MMX® and MMX Multi Matrix System® are registered trademarks of Cosmo Technologies Ltd., Ireland.