Napp Pharmaceuticals Limited

"Depending on the clinical symptoms and the patient’s response, the initial dose can quickly be reduced in steps to a lower maintenance dose."  The word quickly has been removed and in steps has been added.

Section 4.4 Special warnings and precautions
 In addition, low plasma concentrations may occur in 6% -7% of Lodotra doses as observed across all pharmacokinetic studies and 11% in a single pharmacokinetic study when taken according to the recommendations. Words underlined have been added.

Section 5.1 Pharmacodynamic properties
"The efficacy and safety of Lodotra was assessed in two randomised, double-blind controlled studies in patients with active rheumatoid arthritis" has been added.

In the first study, a multi-centre randomised double-blind phase III study of 12 week duration in a total of 288 patients pre-treated with prednisone or prednisolone, the group switching to Lodotra at the same dose showed a mean reduction of 23% in the duration of morning stiffness whereas the duration in the reference group did not change. Details are presented in the following table.  "the first study" has been added.

"The efficacy of Lodotra given on top of a DMARD was confirmed in a second randomised, placebo-controlled trial in patients insufficiently responding to DMARD therapy alone. At 12 weeks the Lodotra patients had a significantly higher ACR20 and ACR50 response rate (46.8% and 22.1%, respectively) compared to placebo patients (29.4% and 10.1%, respectively). There was also a greater mean change in DAS 28 scores from baseline (5.2 for the Lodotra group and 5.1 for the placebo group) to week 12 in the Lodotra group (−1.2 points) as compared with that seen in the placebo group (−0.7 point change).

 In addition, after 12 weeks of therapy the mean duration of morning stiffness was 86.0 minutes (-66 minutes change) in the Lodotra group and 114.1 minutes (-42.6 minutes change) in the placebo group. Lodotra could be safely used in combination with other DMARDs." has been added.