SIMPONI Rx

Rheumatoid Arthritis

The efficacy and safety of Simponi was evaluated in 3 multicenter, randomized, double-blind, controlled trials (Trials RA-1, RA-2, and RA-3), in a total of 1542 patients ≥18 years of age with moderately to severely active RA, diagnosed according to the American College of Rheumatology (ACR) criteria, for at least 3 months prior to administering Simponi. 

Patients were required to have at least 4 swollen and 4 tender joints. Simponi was administered subcutaneously at doses of 50 mg or 100 mg every 4 weeks. Double-blinded controlled efficacy data were collected and analyzed through Week 24. Patients were allowed to continue stable doses of concomitant low dose corticosteroids (equivalent to ≤ 10 mg of prednisone a day) and/or NSAIDs and patients may have received oral MTX during the trials.  

Trial RA-1 included 445 patients who were previously treated (at least 8 to 12 weeks prior to administration of trial agent) with one or more doses of a biologic TNF blocker without a serious adverse reaction. Patients were randomly assigned to receive placebo (N=150), Simponi 50 mg (N=147), or Simponi 100 mg (N=148). Patients were allowed to continue stable doses of concomitant MTX, sulfasalazine (SSZ), and/or hydroxychloroquine (HCQ) during the trial. The use of other DMARDs including cytotoxic agents or other biologics was prohibited.

Trial RA-2 included 444 patients who had active RA despite a stable dose of at least 15 mg/week of MTX and who had not been previously treated with a biologic TNF blocker. Patients were randomly assigned to receive background MTX (N=133), Simponi 50 mg + background MTX (N=89), Simponi 100 mg + background MTX (N=89), or Simponi 100 mg monotherapy (N=133). The use of other DMARDs including SSZ, HCQ, cytotoxic agents, or other biologics was prohibited. 

Trial RA-3 included 637 patients with active RA who were MTX naïve and had not previously been treated with a biologic TNF blocker. Patients were randomized to receive MTX (N=160), Simponi 50 mg + MTX (N=159), Simponi 100 mg + MTX (N=159), or Simponi 100 mg monotherapy (N=159). For patients receiving MTX, MTX was administered at a dose of 10 mg/week beginning at Week 0 and increased to 20 mg/week by Week 8. The use of other DMARDs including SSZ, HCQ, cytotoxic agents, or other biologics was prohibited. 

The primary endpoint in Trial RA-1 and Trial RA-2 was the percentage of patients achieving an ACR 20 response at Week 14 and the primary endpoint in Trial RA-3 was the percentage of patients achieving an ACR 50 response at Week 24. 

Results from all 3 RA trials showed that a greater proportion of patients treated with Symponi plus MTX achieved ACR responses compared with MTX alone. 

In Trial RA-1, treatment with Symponi 50mg ± DMARDs achieved the following ACR responses vs placebo ± DMARDs, respectively:

• ACR 20 

• Week 14: 35% vs 18%

• Week 24: 31% vs 16%

• ACR 50 

• Week 14: 15% vs 7%

• Week 24: 16% vs 4%

• ACR 70 

• Week 14: 10% vs 2% 

• Week 24: 9% vs 2%

In Trial RA-2, treatment with Symponi 50mg plus background MTX achieved the following ACR responses vs background MTX alone, respectively:

• ACR 20 

• Week 14: 55% vs 33%

• Week 24: 60% vs 28%

• ACR 50 

• Week 14: 35% vs 10%

• Week 24: 37% vs 14%

• ACR 70 

• Week 14: 13% vs 4%

• Week 24: 20% vs 5%

In Trial RA-3, treatment with Symponi 50mg plus MTX achieved the following ACR responses vs MTX alone, respectively (data was not collected at week 14):

• ACR 20 (week 24): 62% vs 49%

• ACR 50 (week 24): 40% vs 29%

• ACR 70 (week 24): 24% vs 16%

For Trial RA-2, Symponi 50 mg plus background MTX achieved the following improvements in the individual ACR components at week 14 from baseline vs background MTX, respectively:

• Number of swollen joints (0-66): 62% vs 38%

• Number of tender joints (0-68): 60% vs 30%

• Patient’s assessment of pain (0-10): 55% vs 18%

• Patient’s global assessment of disease activity (0-10): 45% vs 15%

• Physician’s global assessment of disease activity (0-10): 55% vs 35%

• HAQ score (0-3): 29% vs 10%

• CRP (mg/dL): 44% vs 2%

In Trials RA-1 and RA-2, the Simponi 50-mg groups demonstrated a greater improvement compared to the control groups in the change in mean Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline to Week 24: 0.23 vs. 0.03 in RA-1, 0.47 vs. 0.13 in RA-2, respectively. Also in Trials RA-1 and RA-2, the Simponi 50-mg groups compared to the control groups had a greater proportion of HAQ responders (change from baseline > 0.22) at Week 24: 43% vs. 27%, 65% vs. 35%, respectively.

Psoriatic Arthritis

The safety and efficacy of Simponi were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial in 405 adult patients with moderately to severely active PsA (≥ 3 swollen joints and ≥ 3 tender joints) despite NSAID or DMARD therapy (Trial PsA). Patients in this trial had a diagnosis of PsA for at least 6 months with a qualifying psoriatic skin lesion of at least 2 cm in diameter, and did not receive previous treatment with a biologic TNF blocker.

Patients were randomly assigned to placebo (N=113), Simponi 50 mg (N=146), or Simponi 100 mg (N=146) given subcutaneously every 4 weeks. Patients were allowed to receive stable doses of concomitant MTX (≤ 25 mg/week), low dose oral corticosteroids (equivalent to ≤ 10 mg of prednisone a day), and/or NSAIDs during the trial. The use of other DMARDs including SSZ, HCQ, cytotoxic agents, or other biologics was prohibited. The primary endpoint was the percentage of patients achieving ACR 20 response at Week 14.

Results showed that treatment with Symponi 50mg ± MTX achieved the following ACR responses vs placebo ± MTX, respectively:

• ACR 20

• Week 14: 51% vs 9%

• Week 24: 52% vs 12%

• ACR 50

• Week 14: 30% vs 2%

• Week 24: 32% vs 4%

• ACR 70

• Week 14: 12% vs 1%

• Week 24: 19% vs 1%

At week 14, treatment with Symponi 50mg ± MTX achieved the following percent improvements in ACR components vs placebo ± MTX, respectively:

• Number of swollen joints (0-66): 60% vs 8%

• Number of tender joints (0-68): 54% vs 0%

• Patient’s assessment of pain (0-10): 48% vs -1%

• Patient’s global assessment of disease activity (0-10): 49% vs 2%

• Physician’s global assessment of disease activity (0-10): 59% vs 7%

• HAQ score (0-3): 28% vs 0%

• CRP (mg/dL): 40% vs 0%

In Trial PsA, Simponi 50 mg demonstrated a greater improvement compared to placebo in the change in mean Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline to Week 24 (0.33 and -0.01, respectively). In addition, the Simponi 50-mg group compared to the placebo group had a greater proportion of HAQ responders (≥ 0.3 change from baseline) at Week 24: 43% vs. 22%, respectively. 

Ankylosing Spondylitis

The safety and efficacy of Simponi were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial in 356 adult patients with active ankylosing spondylitis according to modified New York criteria for at least 3 months (Trial AS). Patients had symptoms of active disease [defined as a Bath AS Disease Activity Index (BASDAI) ≥ 4 and VAS for total back pain of ≥ 4, on scales of 0 to 10 cm] despite current or previous NSAID therapy.

Patients were randomly assigned to placebo (N=78), Simponi 50 mg (N=138), or Simponi 100 mg (N=140) administered subcutaneously every 4 weeks. Patients were allowed to continue stable doses of concomitant MTX, sulfasalazine (SSZ), hydroxychloroquine (HCQ), low dose corticosteroids (equivalent to < 10 mg of prednisone a day), and/or NSAIDs during the trial. The use of other DMARDs including cytotoxic agents or other biologics was prohibited. The primary endpoint was the percentage of patients achieving an ASsessment in Ankylosing Spondylitis (ASAS) 20 response at Week 14.

Results showed that treatment with Symponi 50mg ± DMARDs achieved the following ASAS responses vs placebo ± DMARDs, respectively:

• ASAS 20 

• Week 14: 59% vs 22%

• Week 24: 56% vs 23%

• ASAS 40 

• Week 14: 45% vs 15%

• Week 24: 44% vs 15%

At week 14, treatment with Symponi 50mg ± DMARDs achieved the following median percent improvements in ASAS components vs placebo ± DMARDs, respectively:

• Patient’s global assessment (0-10): 47% vs 13%

• Total back pain (0-10): 50% vs 9%

• BASFI (0-10): 37% vs -3%

• Inflammation (0-10): 59% vs 6%

Ulcerative Colitis

The safety and efficacy of Simponi were evaluated in 2 multicenter, randomized, double-blind, placebo-controlled clinical trials in patients ≥ 18 years of age (Trials UC-1 and UC-2). 

Trial UC-1 was an induction trial conducted in patients with moderately to severely active ulcerative colitis (UC) who were corticosteroid dependent (i.e., an inability to successfully taper corticosteroids without a return of the symptoms of UC) or had an inadequate response to or had failed to tolerate at least 1 of the following therapies: oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine.

Trial UC-1 was divided into 2 parts. In Part 1 (dose finding), patients were randomly assigned to 1 of 4 treatment groups: 400-mg Simponi administered subcutaneously (SC) at Week 0 and 200 mg at Week 2 (400/200 mg), 200-mg Simponi SC at Week 0 and 100 mg at Week 2 (200/100 mg), 100-mg Simponi SC at Week 0 and 50 mg at Week 2 (100/50 mg), or placebo SC at Weeks 0 and 2. In Part 2 (dose confirming), efficacy was evaluated in 761 patients who were randomly assigned to receive either 400 mg Simponi SC at Week 0 and 200 mg at Week 2, 200-mg Simponi SC at Week 0 and 100 mg at Week 2, or placebo SC at Weeks 0 and 2. Concomitant stable doses of oral aminosalicylates (5-ASA), oral corticosteroids (less than 40 mg/day), azathioprine (AZA), 6-mercaptopurine (6-MP), and/or methotrexate (MTX) were permitted. The primary endpoint was the percent of patients in clinical response at Week 6, defined as a decrease from baseline in the Mayo score by ≥ 30% and ≥ 3 points, accompanied by a decrease in the rectal bleeding subscore of ≥ 1 or a rectal bleeding subscore of 0 (no blood seen) or 1 (streaks of blood with stool less than half the time).

Trial UC-2 was a randomized-withdrawal maintenance trial that evaluated 456 patients who achieved clinical response with Simponi induction and tolerated Simponi treatment. Patients were randomly assigned to receive Simponi 50 mg, Simponi 100 mg or placebo administered subcutaneously every 4 weeks. Patients were permitted to receive concomitant stable doses of oral aminosalicylates, azathioprine, 6-mercaptopurine, and/or methotrexate. Corticosteroids were to be tapered at the start of the maintenance trial. The primary endpoint was the percent of patients maintaining clinical response through Week 54.

The following results from Trial UC-1 showed that a greater proportion of patients in the Simponi 200mg/100mg group achieved clinical response, clinical remission, and had improvement of endoscopic appearance of the mucosa at week 6 compared with the placebo group, respectively:

• Clinical response: 51% vs 30% (treatment difference, 21%; 95% CI, 12-29; P <.0001)

• Clinical remission: 18% vs 6% (treatment difference, 11%; 95% CI, 6-17; P <.0001)

• Improvement of endoscopic appearance of the mucosa: 42% vs 29% (treatment difference, 14%; 95% CI, 5-22; P =.0014)

The following results from Trial UC-2 showed that a greater proportion of patients in the Simponi 100mg group achieved clinical response through week 54 and clinical remission at both week 30 and week 54 compared with the placebo group, respectively:

• Clinical response: 50% vs 31% (treatment difference, 19%; 95% CI, 8-29; P <.001)

• Clinical remission: 28% vs 16% (treatment difference, 12%; 95% CI, 3-21; P =.004)