1.1 Rheumatoid Arthritis (RA)

SIMPONI ARIA, in combination with methotrexate (MTX), is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis.

1.2 Psoriatic Arthritis (PsA)

SIMPONI ARIA is indicated for the treatment of active psoriatic arthritis in patients 2 years of age and older.

1.3 Ankylosing Spondylitis (AS)

SIMPONI ARIA is indicated for the treatment of adult patients with active ankylosing spondylitis.

1.4 Polyarticular Juvenile Idiopathic Arthritis (pJIA)

SIMPONI ARIA is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years of age and older.

2.1 Dosage in Adults with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

The SIMPONI ARIA dosage regimen is 2 mg per kg given as an intravenous infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter. Follow the dilution and administration instructions for SIMPONI ARIA [see Dosage and Administration (2.4)] .

For patients with rheumatoid arthritis (RA), SIMPONI ARIA should be given in combination with methotrexate.

The efficacy and safety of switching between intravenous and subcutaneous formulations and routes of administration have not been established.

2.2 Dosage in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis

The SIMPONI ARIA dosage regimen, based on body surface area (BSA), is 80 mg/m 2given as an intravenous infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter. Follow the dilution and administration instructions for SIMPONI ARIA [see Dosage and Administration (2.4)] .

2.3 Evaluation for Tuberculosis and Hepatitis B Prior to Dosage

Prior to initiating SIMPONI ARIA and periodically during therapy, evaluate patients for active tuberculosis and test for latent infection [see Warnings and Precautions (5.1)] . Prior to initiating SIMPONI ARIA, test patients for hepatitis B viral infection [see Warnings and Precautions (5.1)] .

2.4 Important Administration Instructions

SIMPONI ARIA solution for intravenous infusion should be diluted by a healthcare professional using aseptic technique as follows:

1. Calculate the dosage and the number of SIMPONI ARIA vials needed based on the recommended adult dosage of 2 mg/kg and the patient's weight for RA, PsA and AS. Calculate the dosage and number of SIMPONI ARIA vials needed based on the recommended pediatric dosage of 80 mg/m 2and the patient's body surface area (BSA), for pJIA and pediatric patients with PsA. Each 4 mL vial of SIMPONI ARIA contains 50 mg of golimumab.
2. Check that the solution in each vial is colorless to light yellow. The solution may develop a few fine translucent particles, as golimumab is a protein. Do not use if opaque particles, discoloration, or other foreign particles are present.
3. Dilute the total volume of the SIMPONI ARIA solution with 0.9% Sodium Chloride Injection, USP to a final volume of 100 mL. For example, this can be accomplished by withdrawing a volume of the 0.9% Sodium Chloride Injection, USP from the 100-mL infusion bag or bottle equal to the total volume of SIMPONI ARIA. Slowly add the total volume of SIMPONI ARIA solution to the 100-mL infusion bag or bottle. Gently mix. Discard any unused solution remaining in the vials. Alternatively, SIMPONI ARIA can be diluted using the same method described above with 0.45% Sodium Chloride Injection, USP.
4. Prior to infusion, visually inspect the diluted SIMPONI ARIA solution for particulate matter or discoloration. Do not use if these are present.
5. Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size 0.22 micrometer or less).
6. Do not infuse SIMPONI ARIA concomitantly in the same intravenous line with other agents. No physical biochemical compatibility studies have been conducted to evaluate the use of SIMPONI ARIA with other intravenous agents in the same intravenous line.
7. Infuse the diluted solution over 30 minutes.
8. Once diluted, the infusion solution can be stored for up to 4 hours at room temperature.

5.1 Serious Infections

Patients treated with SIMPONI ARIA are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death.

Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, or parasitic organisms including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, and tuberculosis have been reported with TNF-blockers. Patients have frequently presented with disseminated rather than localized disease. The concomitant use of a TNF-blocker and abatacept or anakinra was associated with a higher risk of serious infections; therefore, the concomitant use of SIMPONI ARIA and these biologic products is not recommended [see Warnings and Precautions (5.6, 5.7)and Drug Interactions (7.2)] .

Treatment with SIMPONI ARIA should not be initiated in patients with an active infection, including clinically important localized infections. Patients greater than 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants such as corticosteroids or methotrexate may be at greater risk of infection. Consider the risks and benefits of treatment prior to initiating SIMPONI ARIA in patients:

• with chronic or recurrent infection;
• who have been exposed to tuberculosis;
• with a history of an opportunistic infection;
• who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or
• with underlying conditions that may predispose them to infection.

5.2 Malignancies

5.3 Congestive Heart Failure

Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF-blockers, including SIMPONI ARIA. Some cases had a fatal outcome. In several exploratory trials of other TNF-blockers in the treatment of CHF, there were greater proportions of TNF-blocker treated patients who had CHF exacerbations requiring hospitalization or increased mortality. SIMPONI ARIA has not been studied in patients with a history of CHF and SIMPONI ARIA should be used with caution in patients with CHF. If a decision is made to administer SIMPONI ARIA to patients with CHF, these patients should be closely monitored during therapy, and SIMPONI ARIA should be discontinued if new or worsening symptoms of CHF appear.

5.4 Demyelinating Disorders

Use of TNF-blockers, including SIMPONI ARIA, has been associated with rare cases of new onset or exacerbation of central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS), and peripheral demyelinating disorders, including Guillain-Barré syndrome. Cases of central demyelination, MS, optic neuritis, and peripheral demyelinating polyneuropathy have rarely been reported in patients treated with golimumab. Prescribers should exercise caution in considering the use of TNF-blockers, including SIMPONI ARIA, in patients with central or peripheral nervous system demyelinating disorders. Discontinuation of SIMPONI ARIA should be considered if these disorders develop.

5.5 Autoimmunity

Treatment with TNF blockers, including SIMPONI ARIA, may result in the formation of antinuclear antibodies (ANA). Rarely, treatment with TNF blockers, may result in the development of a lupus-like syndrome [see Adverse Reactions (6.1)] . If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with SIMPONI ARIA, treatment should be discontinued.

5.6 Use with Abatacept

In controlled trials, the concurrent administration of another TNF-blocker and abatacept was associated with a greater proportion of serious infections than the use of a TNF-blocker alone; and the combination therapy, compared to the use of a TNF-blocker alone, has not demonstrated improved clinical benefit in the treatment of RA. Therefore, the combination of TNF-blockers, including SIMPONI ARIA, and abatacept is not recommended [see Drug Interactions (7.2)] .

5.7 Use with Anakinra

Concurrent administration of anakinra (an interleukin-1 antagonist) and another TNF-blocker was associated with a greater portion of serious infections and neutropenia and no additional benefits compared with the TNF-blocker alone. Therefore, the combination of anakinra with TNF-blockers, including SIMPONI ARIA, is not recommended [see Drug Interactions (7.2)] .

5.8 Switching Between Biological Disease Modifying Antirheumatic Drugs (DMARDs)

Care should be taken when switching from one biologic product to another biologic product since overlapping biological activity may further increase the risk of infection.

5.9 Hematologic Cytopenias

There have been reports of pancytopenia, leukopenia, neutropenia, agranulocytosis, aplastic anemia, and thrombocytopenia in patients receiving golimumab. Caution should be exercised when using TNF-blockers, including SIMPONI ARIA, in patients who have or have had significant cytopenias.

5.10 Vaccinations/Therapeutic Infectious Agents

5.11 Hypersensitivity Reactions

In postmarketing experience, serious systemic hypersensitivity reactions (including anaphylaxis) have been reported following administration of the subcutaneous and intravenous formulations of golimumab including SIMPONI ARIA. Hypersensitivity reactions including hives, pruritus, dyspnea, and nausea, were reported during infusion and generally within an hour after infusion. Some of these reactions occurred after the first administration of golimumab. If an anaphylactic or other serious allergic reaction occurs, administration of SIMPONI ARIA should be discontinued immediately and appropriate therapy instituted.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety data described below are based on one, randomized, double-blind, controlled Phase 3 trial in patients with RA receiving SIMPONI ARIA by intravenous infusion (Trial RA). The protocol included provisions for patients taking placebo to receive treatment with SIMPONI ARIA at Week 16 or Week 24 either by patient response (based on uncontrolled disease activity) or by design, so that adverse events cannot always be unambiguously attributed to a given treatment. Comparisons between placebo and SIMPONI ARIA were based on the first 24 weeks of exposure.

Trial RA included 197 control-treated patients and 463 SIMPONI ARIA-treated patients (which includes control-treated patients who switched to SIMPONI ARIA at Week 16). The proportion of patients who discontinued treatment due to adverse reactions in the controlled phase of Trial RA through Week 24 was 3.5% for SIMPONI ARIA-treated patients and 0.5% for placebo-treated patients. Upper respiratory tract infection was the most common adverse reaction reported in the trial through Week 24 occurring in 6.5% of SIMPONI ARIA-treated patients as compared with 7.6% of control-treated patients, respectively.

6.2 Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to golimumab in the trials described below with the incidence of antibodies in other trials or to other products may be misleading.

Using an enzyme immunoassay (EIA) method, antibodies to golimumab were detected in 13 (3%) golimumab-treated patients following IV administration of SIMPONI ARIA in combination with MTX through Week 24 of Trial RA, of which all were neutralizing antibodies.

A drug-tolerant enzyme immunoassay (drug-tolerant EIA) method for detecting antibodies to golimumab was developed and validated. This method is approximately 16-fold more sensitive than the original EIA method with less interference from golimumab in serum. Through approximately 6 months, the incidence of antibodies to golimumab with the drug-tolerant EIA method for Trials RA, PsA, AS, and pJIA was 21%, 19%, 19% and 31%, respectively. Where tested, approximately one-third to one-half were neutralizing.

Patients with RA, PsA, AS and pJIA who developed antibodies to golimumab generally had lower trough steady-state serum concentrations of golimumab [see Clinical Pharmacology (12.3)].

6.3 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of golimumab. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to golimumab exposure:

General Disorders and Administration Site Conditions:Infusion-related reactions [see Warnings and Precautions (5.11)]

Neoplasm benign and malignant: Melanoma, Merkel cell carcinoma [see Warnings and Precautions (5.2)]

Immune system disorders: Serious systemic hypersensitivity reactions (including anaphylactic reaction) [see Warnings and Precautions (5.11)] , sarcoidosis

Respiratory, thoracic and mediastinal disorders: Interstitial lung disease

Skin and subcutaneous tissue disorders: Skin exfoliation, lichenoid reactions, bullous skin reactions

7.1 Methotrexate

SIMPONI ARIA should be used with MTX for the treatment of RA [see Clinical Studies (14.1)] . Following IV administration, concomitant administration of methotrexate decreases the clearance of SIMPONI ARIA by approximately 9% based on population pharmacokinetics (PK) analysis. In addition, concomitant administration of methotrexate decreases the SIMPONI ARIA clearance by reducing the development of antibodies to golimumab.

7.2 Biologic Products for RA, PsA, AS, and pJIA

An increased risk of serious infections has been seen in clinical RA studies of other TNF-blockers used in combination with anakinra or abatacept, with no added benefit; therefore, use of SIMPONI ARIA with other biologic products, including abatacept or anakinra, is not recommended [see Warnings and Precautions (5.6and 5.7)] . A higher rate of serious infections has also been observed in RA patients treated with rituximab who received subsequent treatment with a TNF-blocker. The concomitant use of SIMPONI ARIA with biologics approved to treat RA, PsA, AS, and pJIA is not recommended because of the possibility of an increased risk of infection.

7.3 Live Vaccines/Therapeutic Infectious Agents

Live vaccines should not be given concurrently with SIMPONI ARIA [see Warnings and Precautions (5.10)] .

Therapeutic infectious agents should not be given concurrently with SIMPONI ARIA [see Warnings and Precautions (5.10)] .

Infants born to women treated with SIMPONI ARIA during their pregnancy may be at increased risk of infection for up to 6 months. Administration of live vaccines to infants exposed to SIMPONI ARIA in uterois not recommended for 6 months following the mother's last SIMPONI ARIA infusion during pregnancy [see Warnings and Precautions (5.10), Use in Specific Populations (8.1)] .

7.4 Cytochrome P450 Substrates

The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (e.g., TNFα) during chronic inflammation. Therefore, it is expected that for a molecule that antagonizes cytokine activity, such as golimumab, the formation of CYP450 enzymes could be normalized. Upon initiation or discontinuation of SIMPONI ARIA in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed.

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

Safety and effectiveness of SIMPONI ARIA for active polyarticular juvenile idiopathic arthritis and PsA have been established in pediatric patients 2 years and older.

Use of SIMPONI ARIA in these age groups is supported by evidence from adequate and well-controlled studies of SIMPONI ARIA in adults with RA and PsA, pharmacokinetic data from adult patients with RA and PsA and pediatric patients with JIA with active polyarthritis, and safety data from a clinical study in 127 pediatric patients 2 to < 18 years of age with JIA with active polyarthritis. The observed pre-dose (trough) concentrations are generally comparable between adults with RA and PsA and pediatric patients with JIA with active polyarthritis, and the PK exposure is expected to be comparable between adult PsA and pediatric patients with PsA [see Adverse Reactions (6.1), Clinical Pharmacology (12.3)and Clinical Studies (14.2, 14.4)] .

Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with golimumab and other TNF-blocking agents [see Warnings and Precautions (5.2)].

The safety and effectiveness in pediatric patients below the age of 2 years have not been established in pJIA or in PsA. The safety and effectiveness of SIMPONI ARIA in pediatric patients with conditions other than pJIA and PsA have not been established.

8.5 Geriatric Use

In Trial RA, the number of patients ages 65 or older was too small to make comparisons with younger SIMPONI ARIA-treated patients. Because there is a higher incidence of infections in the geriatric population in general, caution should be used in treating geriatric patients with SIMPONI ARIA.

12.1 Mechanism of Action

Golimumab is a human monoclonal antibody that binds to both the soluble and transmembrane bioactive forms of human TNFα. This interaction prevents the binding of TNFα to its receptors, thereby inhibiting the biological activity of TNFα (a cytokine protein). There was no evidence of the golimumab antibody binding to other TNF superfamily ligands; in particular, the golimumab antibody did not bind or neutralize human lymphotoxin. Golimumab did not lyse human monocytes expressing transmembrane TNF in the presence of complement or effector cells.

Elevated TNFα levels in the blood, synovium, and joints have been implicated in the pathophysiology of several chronic inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. TNFα is an important mediator of the articular inflammation that is characteristic of these diseases. Golimumab modulated the in vitrobiological effects mediated by TNF in several bioassays, including the expression of adhesion proteins responsible for leukocyte infiltration (E-selectin, ICAM-1 and VCAM-1) and the secretion of proinflammatory cytokines (IL-6, IL-8, G-CSF and GM-CSF). The clinical relevance of these findings is unknown.

12.2 Pharmacodynamics

Following treatment with SIMPONI ARIA in patients with RA, decreases from baseline were observed in tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3), resistin, interleukin-6 (IL-6), macrophage inflammatory protein-1 (MIP-1b), vascular endothelial growth factor (VEGF), serum amyloid A (SAA), S100A12, and high sensitivity C-Reactive protein (hsCRP). Conversely, increases from baseline were observed in tartrate-resistant acid phosphatase (TRAP-5b). The clinical relevance of this information is not known.

12.3 Pharmacokinetics

Golimumab exhibited approximately dose-proportional pharmacokinetics in patients with RA over the dose range of 0.1 to 10.0 mg/kg following a single intravenous dose.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies of golimumab have not been conducted to evaluate its carcinogenic potential. Mutagenicity studies have not been conducted with golimumab. A fertility study conducted in mice using an analogous anti-mouse TNFα antibody administered by the intravenous route at doses up to 40 mg/kg once per week showed no impairment of fertility.

14.1 Rheumatoid Arthritis

The efficacy and safety of SIMPONI ARIA were evaluated in one multicenter, randomized, double-blind, controlled trial (Trial RA, NCT00973479) in 592 patients ≥ 18 years of age with moderately to severely active RA despite concurrent MTX therapy and had not previously been treated with a biologic TNF-blocker. Patients were diagnosed according to the American College of Rheumatology (ACR) criteria, at least 3 months prior to administration of study agent and were required to have at least 6 swollen and 6 tender joints. Patients were randomized to receive either SIMPONI ARIA 2 mg/kg (N=395) or placebo (N=197) over a 30-minute intravenous infusion at Weeks 0, 4 and every 8 weeks thereafter in addition to their weekly maintenance MTX dose (15–25 mg). All patients receiving placebo + MTX received SIMPONI ARIA + MTX after Week 24, but the trial remained blinded until all patients had completed 108 weeks of treatment. Efficacy data were collected and analyzed through Week 52. Patients were allowed to continue stable doses of concomitant low dose corticosteroids (equivalent to ≤ 10 mg of prednisone a day) and/or NSAIDs. The use of other DMARDs including cytotoxic agents or other biologics was prohibited.

The primary endpoint in Trial RA was the percentage of patients achieving an ACR 20 response at Week 14. In Trial RA, the majority of subjects were women (82%) and were Caucasian (80%) with a median age of 52 years and a median weight of 70 kg. Median disease duration was 4.7 years, and 50% of the patients used at least one DMARD other than MTX in the past. At baseline, 81% of patients received concomitant NSAIDs and 81% of patients received low-dose corticosteroids (equivalent to ≤ 10 mg of prednisone a day). The median baseline DAS28-CRP was 5.9 and the median van der Heijde-Sharp score at baseline was 28.5.

Clinical Response

A greater percentage of patients treated with the combination of SIMPONI ARIA + MTX achieved ACR 20 at Week 14 and ACR 50 at Week 24 versus patients treated with the placebo + MTX as shown in Table 2. The percent of patients achieving ACR 20 responses by visit for Trial RA is shown in Figure 1.

Table 2: Trial RA – Proportion of Patients with an ACR Response

Trial RA Active RA, despite MTX
	Placebo + MTX	SIMPONI ARIA + MTX	95% CI *
* For difference in proportions. † N reflects randomized patients.
N †	197	395
ACR 20
Week 14	25%	59%	25.9, 41.4
Week 24	32%	63%	23.3, 39.4
ACR 50
Week 14	9%	30%	15.3, 27.2
Week 24	13%	35%	15.1, 28.4
ACR 70
Week 14	3%	12%	5.3, 13.4
Week 24	4%	18%	8.8, 18.1

Figure 1: Trial RA – Percent of Patients Achieving ACR 20 Response Over Time: Randomized Patients

	The analysis is based on the intent-to-treat population. Last observation carried forward was performed for missing data. Patients who discontinued treatment due to lack of efficacy were counted as non-responders, as were patients who started prohibited medication or failed to achieve at least a 10% improvement in joint counts at Week 16.

The improvement in all components of the ACR response criteria for the SIMPONI ARIA + MTX group was greater compared to the placebo + MTX group in Trial RA as shown in Table 3.

Table 3: Trial RA ─ Components of ACR Response at Week 14

Trial RA Active RA, despite MTX
	Placebo + MTX	SIMPONI ARIA + MTX
Note: All values are means.
* N reflects randomized patients; actual number of patients evaluable for each endpoint may vary.
N *	197	395
Number of swollen joints (0–66)
Baseline	15	15
Week 14	11	6
Number of tender joints (0–68)
Baseline	26	26
Week 14	20	13
Patient's assessment of pain (0–10)
Baseline	6.5	6.5
Week 14	5.6	3.9
Patient's global assessment of disease activity (0–10)
Baseline	6.5	6.5
Week 14	5.5	4.0
Physician's global assessment of disease activity (0–10)
Baseline	6.3	6.2
Week 14	4.9	3.1
HAQ score (0–3)
Baseline	1.6	1.6
Week 14	1.4	1.1
CRP (mg/dL) (0–1)
Baseline	2.2	2.8
Week 14	1.8	0.9

At Week 14, a greater proportion of patients treated with SIMPONI ARIA + MTX achieved a low level of disease activity as measured by a DAS28-CRP less than 2.6 compared with the placebo + MTX group (15% compared to 5%; 95% CI for difference [6.3%, 15.5%]).

14.2 Psoriatic Arthritis

The efficacy and safety of SIMPONI ARIA were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial in 480 patients ≥ 18 years of age with active psoriatic arthritis despite NSAID or DMARD therapy (Trial PsA, NCT02181673). Previous treatment with a biologic was not allowed. Patients in this trial had a diagnosis of PsA for at least six months and had symptoms of active disease [≥5 swollen joints and ≥5 tender joints and a CRP level of ≥ 0.6 mg/dL]. Patients were randomized to either receive SIMPONI ARIA 2 mg/kg (N=241) or placebo (N=239) as a 30-minute intravenous infusion at Weeks 0, 4, 12 and 20. All patients on placebo received SIMPONI ARIA at Week 24, Week 28 and every 8 weeks thereafter through Week 52. Patients in the SIMPONI ARIA treatment group continued to receive SIMPONI ARIA infusions at Week 28 and every 8 weeks through Week 52.

Patients were allowed to continue stable doses of MTX, NSAIDs, and low dose oral corticosteroids (equivalent to ≤ 10 mg of prednisone per day) 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 ACR 20 response at Week 14.

Patients with each subtype of PsA were enrolled, including polyarticular arthritis with absence of rheumatoid nodules (44%), asymmetric peripheral arthritis (19%), distal interphalangeal joint involvement (8.1%), spondylitis with peripheral arthritis (25%), and arthritis mutilans (4.8%). The median duration of PsA disease was 3.5 years, 86% of patients had previously used MTX, and 35% of patients received at least one other DMARD in the past. At baseline, 76% and 54% of the patients had enthesitis and dactylitis, respectively. The median total modified vdH-S score at baseline was 15.5. During the trial, concomitant medications used included MTX (70%), oral corticosteroids (28%), and NSAIDs (71%).

14.3 Ankylosing Spondylitis

The efficacy and safety of SIMPONI ARIA were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial (Trial AS, NCT02186873) in 208 patients ≥ 18 years of age with active ankylosing spondylitis (AS) and inadequate response or intolerance to NSAIDs. Patients had a diagnosis of definite AS for at least 3 months according to modified New York criteria. Patients had symptoms of active disease [Bath AS Disease Activity Index (BASDAI) ≥ 4, VAS for total back pain of ≥ 4, on scales of 0 to 10 cm (0 to 100 mm), and a hsCRP level of ≥ 0.3 mg/dL (3 mg/L)]. Patients were randomized to receive either SIMPONI ARIA 2 mg/kg (N=105) or placebo (N=103) as a 30-minute intravenous infusion at Weeks 0, 4 and 12. All patients on placebo received SIMPONI ARIA at Week 16, Week 20 and every 8 weeks thereafter through Week 52. Patients in the SIMPONI ARIA treatment group continued to receive SIMPONI ARIA infusions at Week 20 and every 8 weeks through Week 52. Patients were allowed to continue stable doses of concomitant MTX, SSZ, hydroxychloroquine (HCQ), low dose oral corticosteroids (equivalent to ≤ 10 mg of prednisone per 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 16.

In Trial AS, the median duration of AS disease was 2.8 years, median duration of inflammatory back pain was 8 years, 90% were HLA-B27 positive, 8.2% had prior joint surgery or procedure, 5.8% had complete ankylosis of the spine, 14% had received prior therapy with one biologic TNF blocker (other than golimumab) and discontinued for reasons other than lack of efficacy within the first 16 weeks of treatment (primary failure), and 76% received at least one DMARD in the past. During the trial, the use of concomitant medications was NSAIDs (88%), SSZ (38%), corticosteroids (26%), MTX (18%), and HCQ (0.5%).

14.4 Polyarticular Juvenile Idiopathic Arthritis (pJIA)

The efficacy of SIMPONI ARIA in pediatric patients with pJIA is based on the pharmacokinetic exposure and extrapolation of the established efficacy of SIMPONI ARIA in RA patients. Efficacy of SIMPONI ARIA was also assessed in a multicenter, open-label, single-arm study in 127 children (2 to < 18 years of age) with JIA with active polyarthritis despite treatment with MTX for at least 2 months (Trial pJIA, NCT02277444). The polyarticular JIA patient subtypes at study entry included: rheumatoid factor negative (43%), rheumatoid factor positive (35%), enthesitis-related arthritis (9%), oligoarticular extended (6%), juvenile psoriatic arthritis (4%), and systemic JIA without systemic manifestations (3%). All patients received SIMPONI ARIA 80 mg/m 2as an intravenous infusion at Week 0, 4, and every 8 weeks through Week 52. Patients continued stable doses of MTX weekly through Week 28; after Week 28, changes in MTX dose were permitted. Efficacy was assessed as supportive endpoints through Week 52. The efficacy was generally consistent with responses in patients with RA.

Vial

Each single-dose vial contains 50 mg of SIMPONI ARIA per 4 mL of solution.

Storage and Handling

Refrigerate SIMPONI ARIA at 36 ⁰F to 46 ⁰F (2 ⁰C to 8 ⁰C) and protect from light. Keep the product in the original carton to protect from light until the time of use. Do not freeze. Do not shake.

If needed, SIMPONI ARIA may be stored at room temperature up to 77 ºF (25 ºC) for a maximum single period of 30 days in the original carton to protect from light. Once SIMPONI ARIA has been stored at room temperature, do not return the product to the refrigerator. If not used within 30 days at room temperature, discard SIMPONI ARIA.

Infections

Inform patients that SIMPONI ARIA may lower the ability of their immune system to fight infections. Instruct the patient of the importance of contacting their doctor if they develop any symptoms of infection, including tuberculosis, invasive fungal infections, and hepatitis B reactivation.

Malignancies

Patients should be counseled about the risk of lymphoma and other malignancies while receiving SIMPONI ARIA. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.

Other Medical Conditions

Advise patients to report any signs of new or worsening medical conditions such as congestive heart failure, demyelinating disorders, autoimmune diseases, liver disease, cytopenias, or psoriasis.

Vaccinations

Inform patients that because SIMPONI ARIA may lower the ability of their immune system to fight infections, they should avoid live vaccines. Inform pregnant patients receiving SIMPONI ARIA that their infants should not receive live vaccines for 6 months following the last infusion of SIMPONI ARIA during pregnancy. Advise patients and infants of women who received SIMPONI ARIA during pregnancy to consult a physician before receiving any immunizations.