Improved Gastrointestinal Tolerance and Patient Preference of Enteric-Coated Sulfasalazine Versus Uncoated Sulfasalazine Tablets in Patients with Rheumatoid Arthritis

Off-label use of uncoated sulfasalazine tablets (TAB) by rheumatoid arthritis (RA) patients in the United States has resulted in poor gastrointestinal (GI) tolerance and compliance. Two studies have shown that treatment of inflammatory bowel disease with enteric-coated sulfasalazine ([EN] Azulfidine ENtabs) resulted in significantly less frequent and severe GI symptoms, compared with treatment with TAB. The current study was conducted to compare GI tolerance of EN and TAB in rheumatoid arthritis (RA) patients. Fifty adult sulfasalazine-naive patients, who displayed stable RA and no significant GI toxicity with nonsteroidal anti-inflammatory drugs and disease-modifying anti-rheumatic drugs at baseline, were randomized to receive 2 g EN or TAB, in a prospective, 10-week, investigator-blinded, crossover study. After an initial 3-week dosing period with either EN or TAB and a 2-week washout, patients were crossed over to the alternative sulfasalazine formulation for a 2nd 3-week dosing period and 2-week follow-up. GI tolerance of EN and TAB in patients who completed both arms of the crossover was assessed bv frequency and intensity of reported adverse events (primary endpoints) and responses to health questionnaires (secondary endpoints).Twelve patients dropped out early because of adverse events and the discontinuation rate was similar in E\ and TAB-treated patients. Patients taking EN who completed the study reported significantly fewer (p < 0.001) GI adverse events (abdominal pain, anorexia, flatulence, diarrhea, heartburn, nausea, and vomiting), compared with those patients taking TAB. The intensity of adverse events was predominantly mild in patients treated with either EN or TAB. Responses to questionnaires were similar in patients taking either formulation of sulfasalazine. However, when asked which treatment period was preferred at the end of the study, 849 of patients completing the study (p < 0.001) chose EN. This study suggests that enteric-coating of sulfasalazine improved GI tolerance and RA patient preference.