14 CLINICAL STUDIES

14.1 Crohn's Disease

The efficacy and safety of CIMZIA were assessed in two double-blind, randomized, placebo-controlled studies in patients aged 18 years and older with moderately to severely active Crohn's disease, as defined by a Crohn's Disease Activity Index (CDAI) of 220 to 450 points, inclusive. CIMZIA was administered subcutaneously at a dose of 400 mg in both studies. Stable concomitant medications for Crohn's disease were permitted.

Study CD1

Study CD1 was a randomized placebo-controlled study in 662 patients with active Crohn's disease. CIMZIA or placebo was administered at Weeks 0, 2, and 4 and then every four weeks to Week 24. Assessments were done at Weeks 6 and 26. Clinical response was defined as at least a 100-point reduction in CDAI score compared to baseline, and clinical remission was defined as an absolute CDAI score of 150 points or lower.

The results for Study CD1 are provided in Table 3. At Week 6, the proportion of clinical responders was statistically significantly greater for CIMZIA-treated patients compared to controls. The difference in clinical remission rates was not statistically significant at Week 6. The difference in the proportion of patients who were in clinical response at both Weeks 6 and 26 was also statistically significant, demonstrating maintenance of clinical response.

Table 3: Study CD1 – Clinical Response and Remission, Overall Study Population
Timepoint	% Response or Remission (95% CI)
Timepoint	Placebo (N = 328)	CIMZIA 400 mg (N = 331)
* Clinical response is defined as decrease in CDAI of at least 100 points, and clinical remission is defined as CDAI ≤ 150 points † p-value < 0.05 logistic regression test
Week 6
Clinical Response*	27% (22%, 32%)	35% (30%, 40%)†
Clinical Remission*	17% (13%, 22%)	22% (17%, 26%)
Week 26
Clinical Response	27% (22%, 31%)	37% (32%, 42%)†
Clinical Remission	18% (14%, 22%)	29% (25%, 34%)†
Both Weeks 6 & 26
Clinical Response	16% (12%, 20%)	23% (18%, 28%)†
Clinical Remission	10% (7%, 13%)	14% (11%, 18%)

Study CD2

Study CD2 was a randomized treatment-withdrawal study in patients with active Crohn's disease. All patients who entered the study were dosed initially with CIMZIA 400 mg at Weeks 0, 2, and 4 and then assessed for clinical response at Week 6 (as defined by at least a 100-point reduction in CDAI score). At Week 6, a group of 428 clinical responders was randomized to receive either CIMZIA 400 mg or placebo, every four weeks starting at Week 8, as maintenance therapy through Week 24. Non-responders at Week 6 were withdrawn from the study. Final evaluation was based on the CDAI score at Week 26. Patients who withdrew or who received rescue therapy were considered not to be in clinical response. Three randomized responders received no study injections, and were excluded from the ITT analysis.

The results for clinical response and remission are shown in Table 4. At Week 26, a statistically significantly greater proportion of Week 6 responders were in clinical response and in clinical remission in the CIMZIA-treated group compared to the group treated with placebo.

Table 4: Study CD2 - Clinical Response and Clinical Remission
	% Response or Remission (95% CI)
	CIMZIA 400 mg ×3 + Placebo N = 210	CIMZIA 400 mg N = 215
* Clinical response is defined as decrease in CDAI of at least 100 points, and clinical remission is defined as CDAI ≤ 150 points † p < 0.05
Week 26
Clinical Response*	36% (30%, 43%)	63% (56%, 69%)†
Clinical Remission*	29% (22%, 35%)	48% (41%, 55%)†

Baseline use of immunosuppressants or corticosteroids had no impact on the clinical response to CIMZIA.

14.2 Rheumatoid Arthritis

The efficacy and safety of CIMZIA were assessed in four randomized, placebo-controlled, double-blind studies (RA-I, RA-II, RA-III, and RA-IV) in patients ≥ 18 years of age with moderately to severely active rheumatoid arthritis diagnosed according to the American College of Rheumatology (ACR) criteria. Patients had ≥ 9 swollen and tender joints and had active RA for at least 6 months prior to baseline. CIMZIA was administered subcutaneously in combination with MTX at stable doses of at least 10 mg weekly in Studies RA-I, RA-II, and RA-III. CIMZIA was administered as monotherapy in Study RA-IV.

Study RA-I and Study RA-II evaluated patients who had received MTX for at least 6 months prior to study medication, but had an incomplete response to MTX alone. Patients were treated with a loading dose of 400 mg at Weeks 0, 2 and 4 (for both treatment arms) or placebo followed by either 200 mg or 400 mg of CIMZIA or placebo every other week, in combination with MTX for 52 weeks in Study RA-I and for 24 weeks in Study RA-II. Patients were evaluated for signs and symptoms and structural damage using the ACR20 response at Week 24 (RA-I and RA-II) and modified Total Sharp Score (mTSS) at Week 52 (RA-I). The open-label extension follow-up study enrolled 846 patients who received 400 mg of CIMZIA every other week.

Study RA-III evaluated 247 patients who had active disease despite receiving MTX for at least 6 months prior to study enrollment. Patients received 400 mg of CIMZIA every four weeks for 24 weeks without a prior loading dose. Patients were evaluated for signs and symptoms of RA using the ACR20 at Week 24.

Study RA-IV (monotherapy) evaluated 220 patients who had failed at least one DMARD use prior to receiving CIMZIA. Patients were treated with CIMZIA 400 mg or placebo every 4 weeks for 24 weeks. Patients were evaluated for signs and symptoms of active RA using the ACR20 at Week 24.

Clinical Response

The percent of CIMZIA-treated patients achieving ACR20, 50, and 70 responses in Studies RA-I and RA-IV are shown in Table 5. CIMZIA-treated patients had higher ACR20, 50 and 70 response rates at 6 months compared to placebo-treated patients. The results in study RA-II (619 patients) were similar to the results in RA-I at Week 24. The results in study RA-III (247 patients) were similar to those seen in study RA-IV. Over the one-year Study RA-I, 13% of CIMZIA-treated patients achieved a major clinical response, defined as achieving an ACR70 response over a continuous 6-month period, compared to 1% of placebo-treated patients.

Table 5: ACR Responses in Studies RA-I, and RA-IV (Percent of Patients)
	Study RA-I Methotrexate Combination (24 and 52 weeks)			Study RA-IV Monotherapy (24 weeks)
Response	Placebo + MTX	CIMZIA* 200 mg + MTX q 2 weeks	CIMZIA* 200 mg + MTX - Placebo + MTX	Placebo	CIMZIA† 400 mg q 4 weeks	CIMZIA† 400 mg - Placebo
Response	N=199	N=393	(95% CI)‡	N=109	N=111	(95% CI)‡
* CIMZIA administered every 2 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 † CIMZIA administered every 4 weeks not preceded by a loading dose regimen ‡ 95% Confidence Intervals constructed using the large sample approximation to the Normal Distribution. § Major clinical response is defined as achieving ACR70 response over a continuous 6-month period
ACR20
Week 24	14%	59%	45% (38%, 52%)	9%	46%	36% (25%, 47%)
Week 52	13%	53%	40% (33%, 47%)	N/A	N/A
ACR50
Week 24	8%	37%	30% (24%, 36%)	4%	23%	19% (10%, 28%)
Week 52	8%	38%	30% (24%, 37%)	N/A	N/A
ACR70
Week 24	3%	21%	18% (14%, 23%)	0%	6%	6% (1%, 10%)
Week 52	4%	21%	18% (13%, 22%)	N/A	N/A
Major Clinical Response§	1%	13%	12% (8%, 15%)

Table 6: Components of ACR Response in Studies RA-I and RA-IV
	Study RA-I				Study RA-IV
Parameter*	Placebo + MTX N=199		CIMZIA† 200 mg + MTX q 2 weeks N=393		Placebo N=109		CIMZIA‡ 400 mg q 4 weeks Monotherapy N=111
	Baseline	Week 24	Baseline	Week 24	Baseline	Week 24	Baseline	Week 24
* For Study RA-I, median is presented. For Study RA-IV, mean (SD) is presented except for CRP which presents geometric mean † CIMZIA administered every 2 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 ‡ CIMZIA administered every 4 weeks not preceded by a loading dose regimen § Study RA-I - Visual Analog Scale: 0 = best, 100 = worst. Study RA-IV - Five Point Scale: 1 = best, 5 = worst ¶ Patient Assessment of Arthritis Pain. Visual Analog Scale: 0 = best, 100 = worst # Health Assessment Questionnaire Disability Index; 0 = best, 3 = worst, measures the patient's ability to perform the following: dress/groom, arise, eat, walk, reach, grip, maintain hygiene, and maintain daily activity All values are last observation carried forward.
Number of tender joints (0-68)	28	27	29	9	28 (12.5)	24 (15.4)	30 (13.7)	16 (15.8)
Number of swollen joints (0-66)	20	19	20	4	20 (9.3)	16 (12.5)	21 (10.1)	12 (11.2)
Physician global assessment§	66	56	65	25	4 (0.6)	3 (1.0)	4 (0.7)	3 (1.1)
Patient global assessment§	67	60	64	32	3 (0.8)	3 (1.0)	3 (0.8)	3 (1.0)
Pain§¶	65	60	65	32	55 (20.8)	60 (26.7)	58 (21.9)	39 (29.6)
Disability index (HAQ)#	1.75	1.63	1.75	1.00	1.55 (0.65)	1.62 (0.68)	1.43 (0.63)	1.04 (0.74)
CRP (mg/L)	16.0	14.0	16.0	4.0	11.3	13.5	11.6	6.4

The percent of patients achieving ACR20 responses by visit for Study RA-I is shown in Figure 1. Among patients receiving CIMZIA, clinical responses were seen in some patients within one to two weeks after initiation of therapy.

*: The same patients may not have responded at each time point

Figure 1 Study RA-I ACR20 Response Over 52 Weeks*

Radiographic Response

In Study RA-I, inhibition of progression of structural damage was assessed radiographically and expressed as the change in modified Total Sharp Score (mTSS) and its components, the Erosion Score (ES) and Joint Space Narrowing (JSN) score, at Week 52, compared to baseline. CIMZIA inhibited the progression of structural damage compared to placebo plus MTX after 12 months of treatment as shown in Table 7. In the placebo group, 52% of patients experienced no radiographic progression (mTSS ≤0.0) at Week 52 compared to 69% in the CIMZIA 200 mg every other week treatment group. Study RA-II showed similar results at Week 24.

Table 7: Radiographic Changes at 6 and 12 months in Study RA-I
	Placebo + MTX N=199 Mean (SD)	CIMZIA 200 mg + MTX N=393 Mean (SD)	CIMZIA 200 mg + MTX – Placebo + MTX Mean Difference
An ANCOVA was fitted to the ranked change from baseline for each measure with region and treatment as factors and rank baseline as a covariate.
mTSS
Baseline	40 (45)	38 (49)	--
Week 24	1.3 (3.8)	0.2 (3.2)	-1.1
Week 52	2.8 (7.8)	0.4 (5.7)	-2.4
Erosion Score
Baseline	14 (21)	15 (24)	--
Week 24	0.7 (2.1)	0.0 (1.5)	-0.7
Week 52	1.5 (4.3)	0.1 (2.5)	-1.4
JSN Score
Baseline	25 (27)	24 (28)	--
Week 24	0.7 (2.4)	0.2 (2.5)	-0.5
Week 52	1.4 (5.0)	0.4 (4.2)	-1.0

Physical Function Response

In studies RA-I, RA-II, RA-III, and RA-IV, CIMZIA-treated patients achieved greater improvements from baseline than placebo-treated patients in physical function as assessed by the Health Assessment Questionnaire – Disability Index (HAQ-DI) at Week 24 (RA-II, RA-III and RA-IV) and at Week 52 (RA-I).

14.3 Polyarticular Juvenile Idiopathic Arthritis

The efficacy of CIMZIA in pediatric patients with pJIA is based on pharmacokinetic exposure and extrapolation of the established efficacy of CIMZIA in RA patients.

The efficacy of CIMZIA was also assessed in a multi-center, open-label study NCT01550003 in 193 patients 2 to 17 years of age with JIA with active polyarthritis with an inadequate response or intolerance to at least 1 DMARD (nonbiologic or biologic). Of those, 105 received the recommended dose. The patients had the following subtypes of JIA: polyarthritis rheumatoid factor-positive (20.0%), polyarthritis rheumatoid factor-negative (44.8%), extended oligoarthritis (13.3%), juvenile psoriatic arthritis (4.8%), and enthesitis-related arthritis (19.0%). Patients could be on stable methotrexate, glucocorticoids, and/or NSAIDs. Efficacy was assessed as secondary endpoints through Week 24. The efficacy was generally consistent with responses in patients with RA.

14.4 Psoriatic Arthritis

The efficacy and safety of CIMZIA were assessed in a multi-center, randomized, double-blind, placebo controlled trial (PsA001) in 409 patients aged 18 years and older with active psoriatic arthritis despite DMARD therapy. Patients in this study had ≥ 3 swollen and tender joints and adult-onset PsA of at least 6 months' duration as defined by the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria, and increased acute phase reactants. Patients had failed one or more DMARDs. Previous treatment with one anti-TNF biologic therapy was allowed, and 20% of patients had prior anti-TNF biologic exposure. Patients receiving concomitant NSAIDs and conventional DMARDs were 73% and 70 % respectively.

Patients received a loading dose of CIMZIA 400 mg at Weeks 0, 2 and 4 (for both treatment arms) or placebo followed by either CIMZIA 200 mg every other week or CIMZIA 400 mg every 4 weeks or placebo every other week. Patients were evaluated for signs and symptoms and structural damage using the ACR20 response at Week 12 and modified Total Sharp Score (mTSS) at Week 24.

Clinical Response

The percentage of CIMZIA-treated patients achieving ACR20, 50 and 70 responses in study PsA001 are shown in Table 8. ACR20 response rates at weeks 12 and 24 were higher for each CIMZIA dose group relative to placebo (95% confidence intervals for CIMZIA 200 mg minus placebo at weeks 12 and 24 of (23%, 45%) and (30%, 51%), respectively and 95% confidence intervals for CIMZIA 400 mg minus placebo at weeks 12 and 24 of (17%, 39%) and (22%, 44%), respectively). The results of the components of the ACR response criteria are shown in Table 9.

Patients with enthesitis at baseline were evaluated for mean improvement in Leeds Enthesitis Index (LEI). CIMZIA-treated patients receiving either 200 mg every 2 weeks or 400 mg every 4 weeks showed a reduction in enthesitis of 1.8 and 1.7, respectively as compared with a reduction in placebo-treated patients of 0.9 at week 12. Similar results were observed for this endpoint at week 24. Treatment with CIMZIA resulted in improvement in skin manifestations in patients with PsA.

Table 8: ACR Responses in Study PsA001 (Percent of Patients)
Response*	Placebo	CIMZIA†200 mg Q2W	CIMZIA‡ 400 mg Q4W
	N=136	N=138	N=135
* Results are from the randomized set. Non-responder Imputation (NRI) is used for patients who escaped therapy or had missing data. † CIMZIA administered every 2 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 ‡ CIMZIA administered every 4 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4
ACR20
Week 12	24%	58%	52%
Week 24	24%	64%	56%
ACR50
Week 12	11%	36%	33%
Week 24	13%	44%	40%
ACR70
Week 12	3%	25%	13%
Week 24	4%	28%	24%

Table 9: Components of ACR Response in Study PsA001
Parameter	Placebo* N=136		CIMZIA† 200 mg Q2W N=138		CIMZIA‡ 400 mg Q4W N=135
	Baseline	Week 12	Baseline	Week 12	Baseline	Week 12
All values presented represent the mean
Results are from the randomized set (either with imputation or observed case)
* Results are from the entire placebo group † CIMZIA administered every 2 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 ‡ CIMZIA administered every 4 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 § Last Observation Carried Forward is used for missing data, early withdrawals or placebo escape ¶ Patient and Physician Global Assessment of Disease Activity, VAS 0=best 100= worst # The Patient Assessment of Arthritis Pain, VAS 0=no pain and 100= most severe pain Þ The HAQ-DI, 4 point scale 0=without difficulty and 3=unable to do
Number of tender joints (0-68)§	20	17	22	11	20	11
Number of swollen joints (0-66)§	10	9	11	4	11	5
Physician global assessment§, ¶	59	44	57	25	58	29
Patient global assessment§, ¶	57	50	60	33	60	40
Pain§, #	60	50	60	33	61	39
Disability index (HAQ)§, Þ	1.30	1.15	1.33	0.87	1.29	0.90
CRP (mg/L)	18.56	14.75	15.36	5.67	13.71	6.34

The percent of patients achieving ACR20 responses by visit for PsA001 is shown in Figure 2.

Randomized Set. Non-responder imputation used for patients with missing data or those who escaped therapy.

*: The same patients may not have responded at each time point.

Figure 2: Study PsA001-ACR20 Response Over 24 Weeks*

Radiographic Response

In study PsA001, inhibition of progression of structural damage was assessed radiographically and expressed as the change in modified total Sharp score (mTSS) and its components, the Erosion Score (ES) and Joint Space Narrowing score (JSN) at week 24, compared to baseline. The mTSS score was modified for psoriatic arthritis by addition of hand distal interphalangeal (DIP) joints.

Patients treated with CIMZIA 200 mg every other week demonstrated greater reduction in radiographic progression compared with placebo-treated patients at Week 24 as measured by change from baseline in total modified mTSS Score (estimated mean score was 0.18 in the placebo group compared with -0.02 in the CIMZIA 200 mg group; 95% CI for the difference was (-0.38, -0.04)). Patients treated with CIMZIA 400 mg every four weeks did not demonstrate greater inhibition of radiographic progression compared with placebo-treated patients at Week 24.

Physical Function Response

In Study PsA001, CIMZIA-treated patients showed improvement in physical function as assessed by the Health Assessment Questionnaire – Disability Index (HAQ-DI) at Week 24 as compared to placebo (estimated mean change from baseline was 0.19 in the placebo group compared with 0.54 in the CIMZIA 200 mg group; 95% CI for the difference was (-0.47, -0.22) and 0.46 in the CIMZIA 400 mg group; 95% CI for the difference was (-0.39, -0.14)).

14.5 Ankylosing Spondylitis

The efficacy and safety of CIMZIA were assessed in one multicenter, randomized, double-blind, placebo-controlled study (AS-1) in 325 patients ≥18 years of age with adult-onset active axial spondyloarthritis for at least 3 months. The majority of patients in the study had active AS.

Patients had active disease as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4, and spinal pain ≥4 on a 0 to 10 Numerical Rating Scale (NRS). Patients must have been intolerant to or had an inadequate response to at least one NSAID. Patients were treated with a loading dose of CIMZIA 400 mg at Weeks 0, 2 and 4 (for both treatment arms) or placebo followed by either 200 mg of CIMZIA every 2 weeks or 400 mg of CIMZIA every 4 weeks or placebo. Concomitant NSAIDs were received by 91% of the AS patients. The primary efficacy variable was the proportion of patients achieving an ASAS20 response at Week 12.

Clinical Response

In study AS-1, at Week 12, a greater proportion of AS patients treated with CIMZIA 200 mg every 2 weeks or 400 mg every 4 weeks achieved ASAS 20 response compared to AS patients treated with placebo (Table 10). Responses were similar in patients receiving CIMZIA 200 mg every 2 weeks and CIMZIA 400 mg every 4 weeks. The results of the components of the ASAS response criteria and other measures of disease activity are shown in Table 11.

Table 10: ASAS Responses in AS patients at Weeks 12 and 24 in study AS-1
Parameters	Placebo N=57	CIMZIA* 200 mg every 2 weeks N=65	CIMZIA† 400 mg every 4 weeks N=56
All percents reflect the proportion of patients who responded in the full analysis set
* CIMZIA administered every 2 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 † CIMZIA administered every 4 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4
ASAS20
Week 12	37%	57%	64%
Week 24	33%	68%	70%
ASAS40
Week 12	19%	40%	50%
Week 24	16%	48%	59%

Table 11: Components of the ASAS response criteria and other measures of disease activity in AS patients at baseline and Week 12 in study AS-1
	Placebo N=57		CIMZIA* 200 mg every 2 weeks N=65		CIMZIA† 400 mg every 4 weeks N=56
	Baseline	Week 12	Baseline	Week 12	Baseline	Week 12
All values presented represent the mean in the full analysis set
* CIMZIA administered every 2 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 † CIMZIA administered every 4 weeks preceded by a loading dose of 400 mg at Weeks 0, 2 and 4 ‡ BASFI is Bath Ankylosing Spondylitis Functional Index § BASDAI is Bath Ankylosing Spondylitis Disease Activity Index ¶ BASMI is Bath Ankylosing Spondylitis Metrology Index
ASAS20 response criteria
-Patient Global Assessment (0-10)	6.9	5.6	7.3	4.2	6.8	3.8
-Total spinal pain (0-10)	7.3	5.8	7.0	4.3	6.9	4.0
-BASFI (0-10)‡	6.0	5.2	5.6	3.8	5.7	3.8
-Inflammation (0-10)	6.7	5.5	6.7	3.8	6.4	3.4
BASDAI (0-10)§	6.4	5.4	6.5	4.0	6.2	3.7
BASMI ¶	4.8	4.4	4.2	3.6	4.3	3.9

The percent of AS patients achieving ASAS20 responses by visit for Study AS001 is shown in Figure 3. Among patients receiving CIMZIA, clinical responses were seen in some AS patients within one to two weeks after initiation of therapy.

Figure 3: Study AS-1: ASAS20 response over 24 weeks in AS patients *

14.6 Non-radiographic Axial Spondyloarthritis

The efficacy and safety of CIMZIA were assessed in a multicenter, randomized, double-blind, placebo-controlled study (nr-axSpA-1) (NCT02552212) in 317 subjects ≥18 years of age with adult-onset active axial spondyloarthritis for at least 12 months. Patients must have had objective signs of inflammation indicated by C-reactive protein (CRP) levels above the upper limit of normal and/or sacroiliitis on magnetic resonance imaging (MRI), indicative of inflammatory disease [positive CRP (> ULN) and/or positive MRI], but without definitive radiographic evidence of structural damage on sacroiliac joints. Patients had active disease as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4, and spinal pain ≥4 on a 0 to 10 Numerical Rating Scale (NRS). Patients must have been intolerant to or had an inadequate response to at least two NSAIDs. Patients were treated with a loading dose of CIMZIA 400 mg at Weeks 0, 2 and 4 or placebo followed by 200 mg of CIMZIA every 2 weeks or placebo. Utilization and dose adjustment of concomitant medications (including NSAIDs, DMARDs, corticosteroids, opioids) were permitted at any time. Patients were allowed to transition to use of open-label CIMZIA at any time at the discretion of the investigator. However, no patients transitioned before Week 12. The primary endpoint was the proportion of patients achieving an Ankylosing Spondylitis Disease Activity Score-Major Improvement (ASDAS-MI) response at Week 52. The ASDAS is a composite weighted scoring system that assesses disease activity, including patient-reported outcomes and CRP levels. A response in ASDAS-Major Improvement (MI) is indicated by a change from baseline of ≥2.0 in the ASDAS and/or reaching the lowest possible ASDAS value.

Clinical Response

In study nr-axSpA-1, at Week 52, a greater proportion of nr-axSpA patients treated with CIMZIA had ASDAS-MI response compared to patients treated with placebo. At both Weeks 12 and 52, ASAS40 responses were greater for patients treated with CIMZIA compared to patients treated with placebo (Table 12). The components of the ASDAS-MI and ASAS response criteria are shown in Table 13.

Table 12: Clinical Responses in nr-axSpA patients at Weeks 12 and 52 in study nr-axSpA-1
Parameters	Placebo	CIMZIA* 200 mg every 2 weeks	CIMZIA 200 mg versus Placebo Odds ratio (95% CI)
	N=158	N=159	CIMZIA 200 mg versus Placebo Odds ratio (95% CI)
* CIMZIA administered every 2 weeks preceded by a loading dose of 400 mg at Weeks 0, 2, and 4 All percents reflect the proportion of patients who were responders and remained in the study and on randomized treatment in the full analysis set. Patients who initiated open-label CIMZIA, or discontinued randomized treatment and remained in the study, or were missing Week 52 visit data were imputed as non-responders.
ASDAS-MI
Week 52	7%	47%	15.2 (7.3 , 31.6)
ASAS-40
Week 12	11%	48%	7.4 (4.1, 13.4)
Week 52	16%	57%	7.4 (4.3, 12.6)

Table 13: Components of the ASDAS-MI and ASAS response criteria and other measures of disease activity in nr-axSpA patients at baseline, and at Week 12 in study nr-axSpA-1
	Placebo		CIMZIA * 200 mg every 2 weeks
	N=158		N=159
	Baseline (SD)	Week 12 (SD)	Baseline (SD)	Week 12 (SD)
Mean and standard deviation in parenthesis were presented based on full analysis set.
* CIMZIA administered every 2 weeks preceded by a loading dose of 400 mg at Weeks 0, 2, and 4 † (BASDAI is Bath Ankylosing Spondylitis Disease Activity Index ‡ The average of BASDAI question 5 and 6 concerning morning stiffness intensity and duration. § BASFI is Bath Ankylosing Spondylitis Functional Index ¶ BASMI is Bath Ankylosing Spondylitis Metrology Index
Total Spinal Pain (0-10)	6.9 (1.8)	6.0 (2.3)	7.0 (1.9)	3.9 (2.6)
Patient Global Assessment of Disease Activity (0-10)	6.7 (2.0)	5.9 (2.4)	6.8 (1.9)	3.8 (2.6)
C-Reactive Protein (mg/L)	15.8 (17.7)	13.2 (17.2)	15.8 (17.8)	6.7 (15.1)
BASDAI (0-10)†	6.8 (1.3)	5.7 (2.1)	6.9 (1.4)	3.9 (2.2)
- Back Pain	7.4 (1.3)	6.2 (2.1)	7.4 (1.4)	4.1 (2.5)
- Peripheral pain and swelling (0-10)	6.2 (2.2)	5.3 (2.5)	6.3 (2.3)	3.7 (2.4)
- Inflammation‡	6.7 (1.8)	5.5 (2.4)	6.9 (1.8)	3.6 (2.4)
BASFI (0-10)§	5.4 (2.2)	4.9 (2.4)	5.4 (2.1)	3.2 (2.3)
BASMI ¶	2.8 (1.4)	2.7 (1.4)	3.0 (1.3)	2.6 (1.4)

The percentage of nr-axSpA patients achieving ASDAS-MI response by visit for study nr-axSpA-1 is shown in Figure 4.

*: The same patients may not have responded at each time point.

Figure 4: Study nr-axSpA-1: ASDAS-MI response over 12 weeks *

In study AS-1, at Week 12, patients with nr-axSpA treated with CIMZIA 200 mg every 2 weeks and CIMZIA 400 mg every 4 weeks had an ASAS 20 response of 42% and 47%, respectively, compared to 20% of patients treated with placebo. The ASAS 40 response in patients treated with CIMZIA 200 mg every 2 weeks and 400 mg every 4 weeks was 30% and 37%, respectively, compared to 11% of patients treated with placebo at Week 12 (see Section 14.4).

Other Health Related Outcomes

In study nr-axSpA-1, at Week 12, patients treated with CIMZIA achieved significantly greater improvement from baseline in the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) score compared to patients treated with placebo.

14.7 Plaque Psoriasis

Three multicenter, randomized, double-blind studies (Study PS-1 [NCT02326298], Study PS-2 [NCT02326272], and Study PS-3 [NCT02346240]) enrolled subjects 18 years of age or older with moderate-to-severe plaque psoriasis who were eligible for systemic therapy or phototherapy. Subjects had a Physician Global Assessment (PGA) of ≥ 3 ("moderate") on a 5-category scale of overall disease severity, a Psoriasis Area and Severity Index (PASI) score ≥ 12, and body surface area (BSA) involvement of ≥ 10%.

Studies PS-1 (234 subjects) and PS-2 (227 subjects) randomized subjects to placebo, CIMZIA 200 mg every other week (following a loading dose of CIMZIA 400 mg at Weeks 0, 2, and 4), or CIMZIA 400 mg every other week. Studies PS-1 and PS-2 assessed the co-primary endpoints of the proportion of patients who achieved a PASI 75 and PGA of "clear" or "almost clear" with at least a 2-point improvement at Week 16. Other evaluated outcomes were PASI 90 at Week 16 and maintenance of efficacy to Week 48.

Study PS-3 randomized 559 subjects to receive placebo, CIMZIA 200 mg every other week (following a loading dose of CIMZIA 400 mg at Weeks 0, 2, and 4), CIMZIA 400 mg every other week up to Week 16, or a biologic comparator (up to Week 12). Study PS-3 assessed the proportion of patients who achieved a PASI 75 at Week 12 as the primary endpoint. Other evaluated outcomes were PGA of "clear" or "almost clear" at Week 16, PASI 75 at Week 16, PASI 90 at Week 16, and maintenance of efficacy to Week 48.

Of the 850 subjects randomized to receive placebo or CIMZIA in these placebo-controlled studies, 29% of patients were naïve to prior systemic therapy for the treatment of psoriasis, 47% had received prior phototherapy or chemophototherapy, and 30% had received prior biologic therapy for the treatment of psoriasis. Of the 850 subjects, 14% had received at least one TNF alpha agent and 16% had received an anti-IL agent. Eighteen percent of subjects reported a history of psoriatic arthritis at baseline.

Across all studies and treatment groups, the mean PASI score at baseline was 20 and ranged from 12 to 69. The baseline PGA score ranged from moderate (70%) to severe (30%). Mean baseline BSA was 25% and ranged from 10% to 96%. Subjects were predominantly men (64%) and White (94%), with a mean age of 46 years.

Clinical Response

Table 15 presents the efficacy results of PS-1, PS-2, and PS-3 at Week 16.

Table 15: Efficacy Results at Week 16 in Adults with Plaque Psoriasis in PS-1, PS-2, and PS-3 [MI*]
	Study PS-1			Study PS-2			Study PS-3†
	Placebo (N=51)	CIMZIA 200mg‡ Q2W (N=95)	CIMZIA 400mg Q2W (N=88)	Placebo (N=49)	CIMZIA 200mg Q2W (N=91)	CIMZIA 400mg Q2W (N=87)	Placebo (N=57)	CIMZIA 200mg Q2W (N=165)	CIMZIA 400mg Q2W (N=167)
* Missing data was imputed using multiple imputation based on the MCMC method. † The primary endpoint in PS-3 was PASI 75 at Week 12. ‡ Subjects received 400 mg of CIMZIA at Weeks 0, 2, and 4, followed by 200 mg every other week. § The co-primary efficacy endpoints at Week 16 in PS-1 and PS-2. ¶ PGA score of 0 (clear) or 1 (almost clear).
PGA of 0 or 1§, ¶	4%	45%	55%	3%	61%	65%	4%	52%	62%
PASI 75§	7%	65%	75%	13%	81%	82%	4%	69%	75%
PASI 90	0%	36%	44%	5%	50%	52%	0%	40%	49%

Examination of age, gender, prior use of biologics, and prior use of systemic therapies did not identify difference in response to CIMZIA among these subgroups.

Based on a post-hoc subgroup analysis in subjects with moderate-to-severe psoriasis, stratified by ≤90 kg or >90 kg, subjects with both lower body weight and lower disease severity may achieve an acceptable response with CIMZIA 200 mg.

Maintenance of Response

In PS-1 and PS-2, among subjects who were PASI 75 responders at Week 16 and received CIMZIA 400 mg every other week, the PASI 75 response rates at Week 48 were 94% and 81%, respectively. In subjects who were PASI 75 responders at Week 16 and received CIMZIA 200 mg every other week, the PASI 75 response rates at Week 48 were 81% and 74%, respectively.

In PS-1 and PS-2, among subjects who were PGA clear or almost clear responders at Week 16 and received CIMZIA 400 mg every other week, the PGA response rates at Week 48 were 79% and 73%, respectively. In subjects who were PGA clear or almost clear responders at Week 16 and received CIMZIA 200 mg every other week, the PGA response rates at Week 48 were 79% and 76%, respectively.

In PS-3 study, subjects who achieved a PASI 75 response at Week 16 were re-randomized to either continue treatment with CIMZIA or be withdrawn from therapy (i.e., receive placebo). At Week 48, 98% of subjects who continued on CIMZIA 400 mg every other week were PASI 75 responders as compared to 36% of subjects who were re-randomized to placebo. Among PASI 75 responders at Week 16 who received CIMZIA 200 mg every other week and were re-randomized to either CIMZIA 200 mg every other week or placebo, there was also a higher percentage of PASI 75 responders at Week 48 in the CIMZIA group as compared to placebo (80% and 46%, respectively).