No New Erosions (% of Patients) 46.2 62.9 16.7 ≤ 0.001 JSN Score 1.0 0.1 0.9 (0.3, 1.4) 0.002 a 40 mg administered fortnightly b Based on rank analysis MTX: Methotrexate *95% confidence intervals for the differences in change scores between MTX and adalimumab In RA Study V, adalimumab-treated patients had a mean duration of rheumatoid arthritis of less than 9 months and had not previously received methotrexate. Structural joint damage was assessed radiographically and expressed as change in modified Total Sharp Score. The Week 52 results are shown in Table 7. A statistically significant difference for change in modified Total Sharp Score and the erosion score was observed at Week 52 and maintained at Week 104. Table 7. Change in Modified Total Sharp Score From Baseline at Weeks 52 and 104 (All Randomised Subjects) in RA Study V MTX n = 257 Adalimumab n = 274 Adalimumab + MTX n = 268 p-valuea p-valueb Week 52 Baseline (mean) 21.8 ± 22.2 18.8 ± 19.0 18.1 ± 20.1 Week 52 (mean) 27.6 ± 24.6 21.8 ± 19.7 19.4 ± 19.9 Change at week 52 (mean ± SD) 5.7 ± 12.7 3.0 ± 11.2 1.3 ± 6.5 < 0.001 < 0.002 Week 104 Baseline (mean) 21.8 ± 22.2 18.8 ± 19.0 18.1 ± 20.1 Week 104 (mean) 32.3 ± 30.0 24.3 ± 23.2 20.0 ± 20.5 Change at week 104 (mean ± SD) 10.4 ± 21.7 5.5 ± 15.8 1.9 ± 8.3 < 0.001 < 0.001
Table 15. Hospitalisations to Week 56 (ITT population) Placebo 40 mg adalimumab fortnightly 40 mg adalimumab every week Combined Adalimumab n=261 n (%) n=260 n (%) n=257 n (%) n= 517 n (%) All-cause Hospitalisation 47 (18) 25 (9.6)* 29 (11.3)* 54 (10.4)* CD – Related Hospitalisation 31 (11.9) 16 (6.2)* 18 (7.0)* 34 (6.6)* Major Surgery 11 (4.2) 1 (0.4)* 2 (0.8)* 3 (0.6)* *p≤ 0.05 Clinical remission results presented in Table 16 remained relatively constant irrespective of previous TNF antagonist exposure. Of in response at Week 4 who attained remission during the study, patients in adalimumab maintenance groups maintained remission for a significantly longer time that patients in the placebo maintenance group (see Figure 5). Among patients who were not in response by Week 12, therapy continued beyond 12 weeks did not result in significantly more responses. The group that received adalimumab every week did not show significantly higher remission rates than the group that received adalimumab fortnightly. trial
immunosuppressants were permitted. The primary efficacy endpoint in both studies was ´time to treatment failure´. Following initial control of disease, a prolongation in time to treatment failure will result in reduced risk of disease flares, inflammation and vision loss. Treatment failure was defined by a outcome based on inflammatory chorioretinal and/or inflammatory retinal vascular lesions, anterior chamber (AC) cell grade, vitreous haze (VH) grade and best corrected visual acuity (BCVA). Study UV I evaluated 217 patients with active uveitis despite treatment with corticosteroids (oral prednisone at a dose of 10 to 60 mg/day). A majority of the 217 patients were female and Caucasian with mean age of 42.7 years. There was no statistically significant demographic difference between the placebo and adalimumab groups. All patients received a standardised dose of prednisone 60 mg/day at study entry followed by a mandatory taper schedule, with complete corticosteroid discontinuation by Week 15. Study UV II evaluated 226 patients with inactive uveitis requiring chronic corticosteroid treatment (oral prednisone 10 to 35 mg/day) at baseline to control their disease. A majority of the 226 patients were female and Caucasian with mean age of 42.5 years. There was no statistically significant demographic difference between the placebo and adalimumab groups. Patients subsequently underwent a mandatory taper schedule, with complete corticosteroid discontinuation by Week 19. Clinical Results Results from both studies demonstrated statistically significant reduction of the risk of treatment failure in patients treated with adalimumab versus patients receiving placebo (See Table 27). Both studies demonstrated an early and sustained effect of adalimumab on the treatment failure rate versus placebo (see Figure 6 and Figure 7).
Nervous system disorders Headache 14 8 Vascular disorders Hypertension 6 3 Flushing 2 1 Page 1 of 2 Footnotes defined on next page of the table Table 33. Adverse Reactions Reported by Patients Treated With Adalimumab during Placebo-Controlled Period of Rheumatoid Arthritis Studies System Organ Classa) Adverse Reactiona) Adalimumab (n=1380) % Control (n=690) % Respiratory, thoracic and mediastinal disorders 7 6 Gastrointestinal disorders Nausea and vomiting 12 11 Abdominal pain 10 6 Sicca syndrome 3 2 GI haemorrhage 2 1 Hepato-biliary disorders Liver enzymes elevated 12 8 Skin and subcutaneous tissue disorders Rash (including exfoliative rash) 14 7 Pruritus 5 1 Dermatitis (including eczema) 3 1 Bruising (including purpura) 2 0 Musculoskeletal, connective tissue and bone disorders Musculoskeletal pain 14 9 Muscle spasms (including blood creatine phosphokinase increased) 5 4 Renal and urinary disorders Haematuria 9 4 Renal impairment 8 4 General disorders and administration site Injection site reaction (including injection site erythema) 20 13 conditions Oedema 5 4 Investigations Coagulation and bleeding disorders (including activated partial thromboplastin time prolonged) 9 4 Blood lactate dehydrogenase increased 2 1 Page 2 of 2 a) MedDRA Polyarticular Juvenile Idiopathic Arthritis