Avsola

Rheumatoid Arthritis  

• The safety and efficacy of infliximab in adult patients with RA were assessed in 2 multicenter, randomized, double-blind, pivotal trials: ATTRACT (Study RA I) and ASPIRE (Study RA II). Concurrent use of stable doses of folic acid, oral corticosteroids (≤10 mg/day) and/or non-steroidal anti-inflammatory drugs (NSAIDs) was permitted. 

• Study RA I was a placebo-controlled study of 428 patients with active RA despite treatment with MTX. Patients received either placebo+MTX or one of 4 doses/schedules of the infliximab+MTX: 3 mg/kg or 10 mg/kg infliximab by IV infusion at Weeks 0, 2 and 6 followed by additional infusions every 4 or 8 weeks in combination with MTX.

• Study RA II was a placebo-controlled study of 3 active treatment arms in 1004 MTX naïve patients of 3 or fewer years’ duration active RA. At randomization, all patients received MTX (optimized to 20 mg/wk by Week 8) and either placebo, 3 mg/kg or 6 mg/kg of infliximab at Weeks 0, 2, and 6 and every 8 weeks thereafter. 

• Results from Study RA I showed that a higher percentage of patients treated with all doses/schedules of infliximab + MTX achieved ACR 20, 50, and 70 compared with placebo + MTX. Improvement was observed as early as Week 2 and maintained through Week 102. In Study RA II, both doses of infliximab + MTX achieved statistically significantly greater ACR 20, 50, and 70 responses compared with MTX alone.

• In both Study RA I and RA II, all doses/schedules of infliximab + MTX had significantly greater improvement from baseline in HAQ-DI and SF-36 physical component summary score averaged over time through Week 54 compared with placebo + MTX and MTX alone.

Ankylosing Spondylitis 

• The safety and efficacy of infliximab were assessed in a randomized, multicenter, double-blind, placebo-controlled study in 279 adult patients with active AS. Patients were randomly assigned to receive either infliximab 5mg/kg or placebo at Weeks 0, 2, 6, 12, and 18.

• Results showed that 60% of patients treated with infliximab achieved a 20% improvement in ASAS response criteria at Week 24 vs 18% of patients treated with placebo (P <.001). At Week 24, 44% and 28% of patients treated with infliximab achieved 50% and 70% improvement in ASAS response criteria vs 9% and 4% of patients treated with placebo (P <.001). 

• There was a low level of disease activity (defined as a value <20 [on a scale of 0-100mm] in each of the 4 ASAS response parameters) achieved in 22% of infliximab-treated patients vs 1% of placebo-treated patients.

• The median improvement from baseline in the general health-related quality-of-life questionnaire SF-36 physical component summary score at Week 24 was 10.2 for the infliximab group vs. 0.8 for the placebo group (P <.001). 

Psoriatic Arthritis  

• A multicenter, double-blind, placebo-controlled study evaluated the safety and efficacy of infliximab  in 200 adults with active PsA despite DMARD or NSAID therapy (≥5 swollen joints and ≥5 tender joints) with 1 or more of the following subtypes: arthritis involving DIP joints (n=49), arthritis mutilans (n=3), asymmetric peripheral arthritis (n=40), polyarticular arthritis (n=100), and spondylitis with peripheral arthritis (n=8). 

• During the 24-week double-blind phase, patients received either infliximab 5 mg/kg or placebo at Weeks 0, 2, 6, 14, and 22 (100 patients in each group). At Week 16, placebo patients with <10% improvement from baseline in both swollen and tender joint counts were switched to infliximab induction (early escape). At Week 24, all placebo-treated patients crossed over to infliximab induction. Dosing continued for all patients through Week 46. 

• Clinical Response:

• 58% of patients treated with infliximab achieved ACR 20 response at Week 14 vs 11% of patients treated with placebo (P <.001). Improvement was observed as early as Week 2.

• At 6 months, 54%, 41%, and 27% of patients treated with infliximab achieved ACR 20, 50, and 70 responses, respectively, vs 16%, 4%, and 2% of patients treated with placebo, respectively.

• At Week 14, 64% of infliximab-treated patients achieved at least 75% improvement from baseline in PASI vs 2% of placebo-treated patients. At 6 months, 60% and 39% of infliximab-treated patients achieved PASI 75 and PASI 90 responses, respectively, vs 1% and 0% of placebo-treated patients.

• Radiographic Response:

• At Week 24, patients treated with infliximab had less radiographic progression than placebo-treated patients (mean change of -0.70 vs. 0.82; P <.001).

• The patients in the infliximab group demonstrated continued inhibition of structural damage at Week 54. Most patients showed little or no change in the vdH-S score during this 12-month study (median change of 0 in both patients who initially received infliximab or placebo).

• Physical Function:

• Patients treated with infliximab demonstrated significant improvement in physical function as assessed by HAQ-DI (median percent improvement in HAQ-DI score from baseline to Week 14 and 24 of 43% for infliximab-treated patients vs 0% for placebo-treated patients).

• During the placebo-controlled portion of the trial (24 weeks), 54% of patients treated with infliximab achieved a clinically meaningful improvement in HAQ-DI (≥0.3 unit decrease) compared to 22% of placebo-treated patients.

Active Crohn’s Disease in Adults  

• The efficacy and safety of single and multiple doses of infliximab were evaluated in 2 randomized, double-blind, placebo-controlled clinical studies in 653 adults with moderate to severe active CD who had an inadequate response to prior conventional therapies.

• In the single-dose trial (N=108):

• 81% (n=22/27) of patients treated with infliximab 5mg/kg achieved clinical response (decrease in CDAI ≥70 points) at Week 4 vs 16% (n=4/25) of patients treated with placebo (P <.001, 2-sided, Fisher’s Exact test).

• 48% (n=13/27) of patients treated with infliximab 5mg/kg achieved clinical remission (CDAI <150) at Week 4 vs 4% (n=1/25) of patients treated with placebo.

• In the multidose trial, 545 patients received infliximab 5mg/kg at Week 0 then randomly assigned to 1 of 3 treatment groups: infliximab 5mg/kg or 10mg/kg at Weeks 2 and 6, then continued every 8 weeks, or placebo. Patients were permitted to use corticosteroid taper after Week 6.

• At Week 2, 57% (n=311/545) of patients were in clinical response.

• At Week 30, 39% (P =.022) and 46% (P =.001) of patients in the 5mg/kg and 10mg/kg maintenance groups, respectively, achieved clinical remission vs 25% of patients in the placebo maintenance group.

• At Week 54, 25% (P =.059) and 34% (P =.005) of patients in the 5mg/kg and 10mg/kg maintenance groups, respectively, in remission were able to discontinue corticosteroid use vs 11% of patients in the placebo maintenance group.

• At Weeks 30 and 54, there was significant improvement observed in the 5mg/kg and 10mg/kg groups in the disease-specific inflammatory bowel disease (IBDQ) and in the physical component summary score of the general health-related quality of life questionnaire SF-36 compared with placebo.

Fistulizing Crohn’s Disease in Adults  

• The safety and efficacy of infliximab were assessed in 2 randomized, double-blind, placebo-controlled studies in adult patients with fistulizing CD with fistula(s) that were of at least 3 months duration. Patients were allowed to use concurrently with stable doses of corticosteroids, 5-aminosalicylates, antibiotics, MTX, 6-MP and/or AZA.

• Study 1 included 94 adults who received 3 doses of either placebo or infliximab at Weeks 0, 2, and 6. Fistula response was defined as at least a 50% reduction in number of enterocutaneous fistulas draining upon gentle compression on at least 2 consecutive visits without an increase in medication or surgery for CD.

• 68% (n=21/31) of patients in the 5mg/kg infliximab arm (P =.002) and 56% (n=18/32) of patients in the 10mg/kg infliximab arm (P =.021) achieved fistula response vs 26% (n=8/31) of patients in the placebo arm.

• Patients treated with infliximab had a median time to onset of response of 2 weeks and a median duration of response of 12 weeks.

• 52% of patients treated with infliximab achieved closure of all fistulas vs 13% of patients treated with placebo (P <.001).

• Study 2 included adults who had to have at least 1 draining enterocutaneous (perianal, abdominal) fistula. All patients received infliximab 5mg/kg at Weeks 0, 2, and 6, then were randomly assigned to receive placebo or infliximab 5mg/kg maintenance at Week 14 and every 8 weeks through Week 46. The primary endpoint was time from randomization to loss of response among those patients who were in fistula response.

• At Week 14, 65% (n=177/273) of patients were in fistula response.

• At Week 54, 38% (n=33/87) of patients treated with infliximab had no draining fistulas vs 22% (n=20/90) of patients treated with placebo (P =.02).

• Of the placebo maintenance patients, 66% (n=25/38) responded to infliximab 5mg/kg, and 57% (n=12/21) of maintenance patients on infliximab responded to 10mg/kg.

Pediatric Crohn’s Disease

• The efficacy and safety of infliximab was assessed in a randomized, open-label study (Study Peds Crohns) in 112 patients 6 to 17 years of age with moderately to severely active CD who had an inadequate response to conventional therapies. All patients were required to be on a stable dose of 6-MP, AZA, or MTX.

• Patients received induction dosing of infliximab 5mg/kg at Weeks 0, 2, and 6. At Week 10, 103 patients were randomly assigned to receive a maintenance regimen of infliximab 5mg/kg given either every 8 weeks or every 12 weeks.

• At Week 10, 88% of patients achieved clinical response, defined as a decrease from baseline in the PCDAI score of ≥15 points and total PCDAI score of ≤30 points, and 59% achieved clinical remission, defined as PCDAI score of  ≤10 points.

• At Week 30 and Week 54, a greater proportion of patients in the every 8-week treatment group achieved clinical response vs the every 12-week treatment group (73% [P <.01] vs 47% at Week 30, and 64% [P <.01] vs 33% at Week 54).

• At Week 30 and Week 54, a greater proportion of patients in the every 8-week treatment group achieved clinical remission vs the every 12-week treatment group (60% [P <.05] vs 35% at Week 30, and 56% [P <.01] vs 24% at Week 54).

• At Week 30, 46% and 33% of patients in the every 8-week and every 12-week maintenance groups, respectively, were able to discontinue corticosteroids while in remission. 

• At Week 54, 46% and 17% of patients in the every 8-week and every 12-week maintenance groups, respectively, were able to discontinue corticosteroids while in remission. 

Adult Ulcerative Colitis

• The safety and efficacy of infliximab were assessed in 2 randomized, double-blind, placebo-controlled clinical studies in 728 adult patients with moderately to severely active UC (Mayo score 6 to 12 [of possible range 0 to 12], Endoscopy subscore ≥2) with an inadequate response to conventional oral therapies (Studies UC I and UC II). Patients were allowed to use concomitant treatment with stable doses of aminosalicylates, corticosteroids, and/or immunomodulatory agents.

• Patients were randomly assigned to receive either placebo or infliximab 5mg/kg or 10mg/kg at Weeks 0, 2, 6, and every 8 weeks thereafter through Week 46 in Study UC I, and at Weeks 0, 2, 6, and every 8 weeks thereafter through Week 22 in Study UC II.

• Study UC I included adults who failed to respond or were intolerant to oral corticosteroids, 6-MP, or AZA. Study UC II included adults who failed to respond or were intolerant to the above treatments and/or aminosalicylates.

• Clinical response was 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 or 1. 

• Results from Study UC I showed that a greater proportion of patients treated with infliximab 5mg/kg and 10mg/kg achieved clinical response, clinical remission and mucosal healing vs placebo:

• Clinical Response

• Week 8: 69% (P <.001) vs 62% (P <.001) vs 37%

• Week 30: 52% (P <.001) vs 51% (P <.01) vs 30%

• Week 54: 45% (P <.001) vs 44% (P <.001) vs 20%

• Sustained Response

• Clinical response at both Week 8 and Week 30: 49% (P <.001) vs 46% (P <.001) vs 23%

• Clinical response at Weeks 8, 30, and 54: 39% (P <.001) vs 37% (P <.001) vs 14%

• Clinical Remission

• Week 8: 39% (P <.001) vs 32% (P <.01) vs 15%

• Week 30: 34% (P <.01) vs 37% (P <.001) vs 16%

• Week 54: 35% (P <.01) vs 34% (P <.001) vs 17%

• Sustained Remission

• Clinical remission at both Week 8 and Week 30: 23% (P <.01) vs 26% (P <.001) vs 8%

• Clinical remission at Weeks 8, 30, and 54: 20% (P <.01) vs 20% (P <.01) vs 7%

• Mucosal Healing

• Week 8: 62% (P <.001) vs 59% (P <.001) vs 34%

• Week 30: 50% (P <.001) vs 49% (P <.001) vs 25%

• Week 54: 45% (P <.001) vs 47% (P <.001) vs 18%

• Results from Study UC II showed that a greater proportion of patients treated with infliximab 5mg/kg and 10mg/kg achieved clinical response, clinical remission and mucosal healing vs placebo:

• Clinical Response

• Week 8: 65% (P <.001) vs 69% (P <.001) vs 29%

• Week 30: 47% (P <.001) vs 60% (P <.01) vs 26%

• Sustained Response

• Clinical response at both Week 8 and Week 30: 41% (P <.001) vs 53% (P <.001) vs 15%

• Clinical Remission

• Week 8: 34% (P <.001) vs 28% (P <.001) vs 6%

• Week 30: 26% (P <.01) vs 36% (P <.001) vs 11%

• Sustained Remission

• Clinical remission at both Week 8 and Week 30: 15% (P <.001) vs 23% (P <.001) vs 2%

• Mucosal Healing

• Week 8: 60% (P <.001) vs 62% (P <.001) vs 31%

• Week 30: 46% (P <.01) vs 57% (P <.001) vs 30%

Pediatric Ulcerative Colitis

• The safety and efficacy of infliximab for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients aged 6 years and older with moderately to severely active UC who have had an inadequate response to conventional therapy are supported by evidence from adequate and well-controlled studies of infliximab in adults. 

• The open-label pediatric UC trial included 60 pediatric patients 6 through 17 years of age with moderately to severely active UC (Mayo score of 6 to 12; Endoscopic subscore ≥2) and an inadequate response to conventional therapies. Patients received induction dosing of infliximab 5mg/kg at Weeks 0, 2, and 6, then patient responders were randomly assigned to a maintenance regimen of infliximab 5mg/kg at Week 8 every 8 weeks through Week 46 or every 12 weeks through Week 42.

• Clinical response was 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 or 1. Clinical remission at Week 8 was measured by the Mayo score, defined as a Mayo score of ≤2 points with no individual subscore >1.

• At Week 8, 44 patients were in clinical response. Of 32 patients taking concomitant immunomodulators at baseline, 23 achieved clinical response at Week 8 compared with 21 out of 28 of patients not taking concomitant immunomodulators at baseline.

• At Week 8, 24 of 60 patients were in clinical remission as measured by the Mayo score and 17 of 51 patients were in remission as measured by the PUCAI score.

• At Week 54, 8 of 21 patients in the every 8-week maintenance group and 4 of 22 patients in the every 12-week maintenance group achieved clinical remission as measured by the PUCAI score.

Plaque Psoriasis

The 3 randomized, double-blind, placebo-controlled studies (EXPRESS, EXPRESS II, SPIRIT) evaluated the efficacy and safety of infliximab in patients 18 years of age and older with chronic, stable Ps involving ≥10% BSA, a minimum PASI score of 12, and who were candidates for systemic therapy or phototherapy. Patients were not allowed to use concomitant anti-psoriatic therapies during the study, with the exception of low-potency topical corticosteroids on the face and groin after Week 10 of study initiation. The primary endpoint was the proportion of patients who achieved a reduction in score of at least 75% from baseline at Week 10 by the PASI (PASI 75).

Study I - EXPRESS 

• The study included 378 patients who were randomly assigned to receive either placebo or infliximab 5mg/g at Weeks 0, 2, and 6 (induction therapy), followed by maintenance therapy every 8 weeks. At Week 24, the placebo group crossed over to infliximab induction therapy, followed by maintenance therapy every 8 weeks.

• At Week 10, 80% (n=242) of patients treated with infliximab 5mg/kg achieved PASI 75 vs 3% (n=2) of patients treated with placebo (P <.001).

• At Week 10, 80% (n=242) of patients treated with infliximab 5mg/kg achieved sPGA vs 4% (n=3) of patients treated with placebo (P <.001).

Study II - EXPRESS II

• The study included 835 patients who were randomly assigned to receive either placebo or infliximab 3mg/kg or 5mg/kg at Weeks 0, 2, and 6 (induction therapy). At Week 14, patients in each infliximab dose group were randomly assigned to receive either infliximab every 8 weeks or as needed maintenance treatment through Week 46.

• At Week 10, 70% (n=220) and 75% (n=237) of patients treated with infliximab 3mg/kg and 5mg/kg, respectively, achieved PASI 75 vs 2% (n=4) of patients treated with placebo (P <.001 for both).

• At Week 10, 69% (n=217) and 75% (n=234) of patients treated with infliximab 3mg/kg and 5mg/kg, respectively, achieved rPGA vs 1% (n=2) of patients treated with placebo (P <.001 for both).

• The every 8-week maintenance group had a greater percentage of patients maintaining PASI 75 through week 50 vs the as-needed or PRN group. The best response was maintained with the 5mg/kg every 8-week dose.

Study III - SPIRIT

• The study included 249 patients who had previously received either psoralen plus ultraviolet A treatment (PUVA) or other systemic therapy for their psoriasis. Patients were randomly assigned to receive either placebo or infliximab 3mg/kg or 5mg/kg at Weeks 0, 2, and 6. At Week 26, patients with a sPGA score of moderate or worse (score ≥3) received an additional dose of the randomized treatment.

• At Week 10, 72% (n=71) and 88% (n=87) of patients treated with infliximab 3mg/kg and 5mg/kg, respectively, achieved PASI 75 vs 6% (n=3) of patients treated with placebo (P <.001 for both).

• At Week 10, 72% (n=71) and 90% (n=89) of patients treated with infliximab 3mg/kg and 5mg/kg, respectively, achieved sPGA vs 10% (n=5) of patients treated with placebo (P <.001 for both).