Simponi

• Overview
• Consumer Information
• Professional Information

 

Simponi Side Effects Center

What Is Simponi?

Simponi (golimumab injection) is a human IgG1k monoclonal antibody used to treat rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Simponi is sometimes used with another medication called methotrexate (Rheumatrex, Trexall). Simponi works by blocking a protein (tumor necrosis factor or TNF) found in the body's immune system that causes joint swelling and damage.

What Are Side Effects of Simponi?

Common side effects of Simponi include:

• dizziness,
• cold symptoms (stuffy nose, sneezing, sore throat), or
• injection site reactions (redness, itching, pain, or swelling).

Tell your doctor if you have serious side effects of Simponi including:

• easy bruising or bleeding,
• numbness or tingling of the hands or feet,
• unsteadiness,
• unexplained muscle weakness,
• vision changes,
• muscle or joint pain,
• butterfly-shaped rash on the nose and cheeks,
• symptoms of heart failure (including swelling ankles or feet, trouble breathing, unusual tiredness),
• signs of infection (such as fever/chills/cough/persistent sore throat, unusual sweating), or
• symptoms of liver damage (including dark urine, persistent nausea/vomiting/loss of appetite, stomach/abdominal pain, or yellow eyes or skin).

Dosage for Simponi

The Simponi dose regimen is 50 mg administered by subcutaneous (SC) injection once a month.

What Drugs, Substances, or Supplements Interact with Simponi?

Simponi may interact with abatacept, anakinra, rituximab, blood thinners, cyclosporine, digoxin, theophylline, seizure medications, or heart rhythm medications. Tell your doctor all medications you use.

Simponi During Pregnancy and Breastfeeding

During pregnancy, Simponi should be used only when prescribed. It is unknown if this drug passes into breast milk. Because of the potential risk to the infant, consult your doctor before breastfeeding.

Additional Information

Our Simponi (golimumab injection) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Simponi Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives, itching; nausea; chest pain, difficulty breathing; swelling of your face, lips, tongue, or throat.

You may get infections more easily, even serious or fatal infections. Call your doctor right away if you have signs of infection such as:

• fever, chills, night sweats, muscle aches, feeling very tired;
• cough, bloody mucus, shortness of breath;
• weight loss;
• skin sores with pain, warmth, or redness;
• diarrhea, stomach pain; or
• increased urination, or burning when you urinate.

Also call your doctor at once if you have:

• skin growths or changes in skin appearance;
• swelling in your lower legs;
• vision changes;
• numbness or tingly feeling, weakness in your arms or legs;
• pale skin, easy bruising or bleeding;
• liver problems--right-sided upper stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
• new or worsening symptoms of lupus--muscle or joint pain, and a skin rash on your cheeks or arms that worsens in sunlight; or
• signs of psoriasis--red or scaly patches of skin, flaking, pus.

Common side effects may include:

• infections, cold or flu symptoms;
• abnormal liver function tests;
• high blood pressure;
• rash; or
• pain, itching, redness, or swelling where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Simponi (Golimumab Injection)

 

Simponi Professional Information

SIDE EFFECTS

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 5 pooled, randomized, double-blind, controlled Phase 3 trials in patients with RA, PsA, and AS (Trials RA-1, RA-2, RA-3, PsA, and AS) [see Clinical Studies]. These 5 trials included 639 control-treated patients and 1659 SIMPONI-treated patients including 1089 with RA, 292 with PsA, and 278 with AS. The safety data in 1233 SIMPONI-treated patients with ulcerative colitis from 3 pooled, randomized, double-blind, controlled Phase 2/3 trials are also described below (Trials UC-1, UC-2, and UC-3) [see Clinical Studies]. The proportion of patients who discontinued treatment due to adverse reactions in the controlled Phase 3 trials through Week 16 in RA, PsA and AS was 2% for SIMPONI-treated patients and 3% for placebo-treated patients. The most common adverse reactions leading to discontinuation of SIMPONI in the controlled Phase 3 trials in RA, PsA and AS through Week 16 were sepsis (0.2%), alanine aminotransferase increased (0.2%), and aspartate aminotransferase increased (0.2%). The most common adverse drug reactions leading to discontinuation through Week 60 of the UC trials in patients who received SIMPONI induction and 100 mg during maintenance compared with patients who received SIMPONI induction and placebo during maintenance were tuberculosis (0.3% vs. 0.6%) and anemia (0.3% vs. 0%), respectively.

The most serious adverse reactions were:

• Serious Infections [see WARNINGS AND PRECAUTIONS]
• Malignancies [see WARNINGS AND PRECAUTIONS]

Upper respiratory tract infection and nasopharyngitis were the most common adverse reactions reported in the combined Phase 3 RA, PsA and AS trials through Week 16, occurring in 7% and 6% of SIMPONI-treated patients as compared with 6% and 5% of control-treated patients, respectively.

Infections

In controlled Phase 3 trials through Week 16 in RA, PsA, and AS, infections were observed in 28% of SIMPONI-treated patients compared to 25% of control-treated patients. For serious infections, see the Warnings and Precautions section [see WARNINGS AND PRECAUTIONS]. In the controlled Phase 2/3 trial of SIMPONI induction through Week 6 in UC, the rates of infections were similar in SIMPONI 200/100 mg-treated patients and placebo-treated patients, or approximately 12%. Through Week 60, the incidence per patient year of infections was similar in patients who received SIMPONI induction and 100 mg during maintenance compared with patients who received SIMPONI induction and placebo during the maintenance portion of the UC trial.

Demyelinating Disorders

In the controlled Phase 2/3 trial of SIMPONI induction through Week 6, no cases of demyelination were observed in SIMPONI 200/100 mg-treated patients or placebo-treated patients. Through Week 60, there were no cases of demyelination in the SIMPONI 100-mg group during maintenance. One case of CNS demyelination was observed in the placebo maintenance group in a patient who received SIMPONI 400/200 mg during induction.

Liver Enzyme Elevations

There have been reports of severe hepatic reactions including acute liver failure in patients receiving TNF blockers. In controlled Phase 3 trials of SIMPONI in patients with RA, PsA, and AS through Week 16, ALT elevations ≥ 5 x ULN occurred in 0.2% of control-treated patients and 0.7% of SIMPONI-treated patients and ALT elevations ≥ 3 x ULN occurred in 2% of control-treated patients and 2% of SIMPONI-treated patients. Since many of the patients in the Phase 3 trials for RA, PsA, and AS were also taking medications that cause liver enzyme elevations (e.g., NSAIDs, MTX), the relationship between SIMPONI and liver enzyme elevation is not clear.

In Phase 2/3 UC trials, the incidence of ALT elevations ≥ 5 x ULN was similar in SIMPONI-treated patients and placebo-treated patients, or approximately 1%, with an average duration of follow-up of 46 weeks and 18 weeks, respectively. ALT elevations ≥ 3 x ULN occurred in 2.0% of SIMPONI-treated patients compared with 1.5% of placebo-treated patients with an average duration of follow-up of 46 weeks and 18 weeks, respectively.

Autoimmune Disorders And Autoantibodies

In the controlled Phase 3 trials in patients with RA, PsA, and AS through Week 14, there was no association of SIMPONI treatment and the development of newly positive anti-dsDNA antibodies. In Phase 3 trials in RA, PsA, and AS through 1 year of follow-up, 4.0% of SIMPONI-treated patients and 2.6% of control patients were newly antinuclear antibody (ANA)-positive (at titers of 1:160 or greater). The frequency of anti-dsDNA antibodies at 1 year of follow-up was uncommon in patients who were anti-dsDNA negative at baseline. Through Week 60 of the UC trials, 3.5% of patients who received SIMPONI induction and 100 mg during maintenance were newly ANA-positive (at titers of 1:160 or greater) compared with 3.5% of patients who received SIMPONI induction and placebo during the maintenance portion of the UC trial. The frequency of anti-dsDNA antibodies at 1 year of follow-up in patients who were anti-dsDNA negative at baseline was 0.5% in patients receiving SIMPONI induction and 100 mg during maintenance compared with 0% in patients who received SIMPONI induction and placebo during maintenance [see WARNINGS AND PRECAUTIONS].

Injection Site Reactions

In controlled Phase 3 trials through Week 16 in RA, PsA and AS, 6% of SIMPONI-treated patients had injection site reactions compared with 2% of control-treated patients. The majority of the injection site reactions were mild and the most frequent manifestation was injection site erythema.

In the controlled Phase 2/3 trial through Week 6 in UC, 3.4% of SIMPONI-treated patients had injection site reactions compared with 1.5% in control-treated patients. The majority of the injection site reactions were mild and moderate and the most frequent manifestation was injection site erythema.

In controlled Phase 2 and 3 trials in RA, PsA, AS, and Phase 2/3 UC trials, no patients treated with SIMPONI developed anaphylactic reactions.

Other Adverse Reactions

Table 1 summarizes the adverse drug reactions that occurred at a rate of at least 1% in the SIMPONI ± DMARD group and with a higher incidence than in the placebo ± DMARD group during the controlled period of the 5 pooled Phase 3 trials through Week 16 in patients with RA, PsA, and AS.

Table 1: Adverse Drug Reactions Reported by ≥ 1% of SIMPONI-Treated Patients and With a Higher Incidence Than Placebo-Treated Patients in the Phase 3 Trials of RA, PsA, and AS through Week 16^a

	SIMPONI ± DMARDs	Placebo ± DMARDs
Patients treated	1659	639
Adverse Reaction
Infections and infestations
Upper respiratory tract infection (nasopharyngitis, pharyngitis, laryngitis, and rhinitis)	16%	13%
Viral infections (such as influenza and herpes)	5%	3%
Bronchitis	2%	1%
Superficial fungal infections	2%	1%
Sinusitis	2%	1%
General disorders and administration site conditions
Injection site reaction (injection site erythema, urticaria, induration, pain, bruising, pruritus, irritation, paresthesia)	6%	2%
Investigations
Alanine aminotransferase increased	4%	3%
Aspartate aminotransferase increased	3%	2%
Vascular disorders
Hypertension	3%	2%
Nervous system disorders
Dizziness	2%	1%
Paresthesia	2%	1%
Gastrointestinal disorders
Constipation	1%	<1%
a Patients may have taken concomitant MTX, sulfasalazine, hydroxychloroquine, low dose corticosteroids (≤ 10 mg of prednisone/day or equivalent), and/or NSAIDs during the trials).

Less Common Clinical Trial Adverse Drug Reactions

Adverse drug reactions that occurred <1% in SIMPONI-treated patients during the SIMPONI clinical trials that do not appear in the Warnings and Precautions section included the following events listed by system organ class:

Infections and infestations: Septic shock, atypical mycobacterial infection, pyelonephritis, arthritis bacterial, bursitis infective

Neoplasms benign, malignant and unspecified: Leukemia

Skin and subcutaneous tissue disorders: Psoriasis (new onset or worsening, palmar/plantar and pustular), vasculitis (cutaneous)

Vascular disorders: Vasculitis (systemic)

Other Clinical Trial Adverse Drug Reactions In Ulcerative Colitis Clinical Trials

In the Phase 2/3 trials in UC evaluating 1233 SIMPONI-treated patients, no new adverse drug reactions were identified and the frequency of adverse drug reactions was similar to the safety profile observed in patients with RA, PsA and AS.

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.

Results From The EIA Method

Using an enzyme immunoassay (EIA method), antibodies to golimumab were detected in 57 (4%) of SIMPONI-treated patients across the Phase 3 RA, PsA and AS trials through Week 24. Similar rates were observed in each of the 3 indications. Patients who received SIMPONI with concomitant MTX had a lower proportion of antibodies to golimumab than patients who received SIMPONI without MTX (approximately 2% vs. 7%, respectively).

With the EIA method, the presence of serum concentrations of golimumab can interfere with the detection of antibodies to golimumab leading to inconclusive results. In UC trials, 34 (3%), 341 (28%) and 823 (69%) of SIMPONI-treated patients were positive, negative and inconclusive for antibodies to golimumab, respectively. Treatment with concomitant immunomodulators (AZA, 6-MP or MTX) resulted in a lower proportion of patients with antibodies to golimumab than patients receiving SIMPONI without immunomodulators (2% vs. 4%, respectively).

Of the patients with a positive antibody response to golimumab in the Phase 2 and 3 trials, most were determined to have neutralizing antibodies to golimumab as measured by a cell-based functional assay.

Results From The Drug-Tolerant EIA Method

A drug-tolerant enzyme immunoassay (drug-tolerant EIA) method for detecting antibodies to golimumab was developed and validated, which eliminated the inconclusive category as reported above. This method is approximately 16-fold more sensitive than the original EIA method with less interference from golimumab in serum.

Based on the drug tolerant EIA method, 246 (23%) of SIMPONI-treated patients across the Phase 3 RA, PsA and AS trials, antibodies to golimumab were detected in 59 (16%), 106 (28%), and 81 (24%) patients, respectively. Treatment with concomitant MTX resulted in a lower proportion of patients with antibodies to golimumab than in patients receiving SIMPONI without MTX in RA patients (7% vs. 35%), in PsA patients (18% vs. 38%) and in AS patients (6% vs. 29%). A trend of decreasing drug concentrations with increasing antibody titers was observed. While an overall decrease in clinical efficacy for ADA positive patients compared with ADA negative patients was not observed in patients with RA (ACR 20: 75% vs. 75%), PsA (ACR 20: 72% vs. 66%) and AS (ASAS 20: 57% vs. 65%), higher titer antibodies may be associated with diminished efficacy.

In the UC trials, 254 (21%) of SIMPONI-treated patients were positive for antibodies to golimumab through week 54 while the remaining 941 (79%) patients were negative. Treatment with concomitant immunomodulators (AZA, 6-MP or MTX) in the UC trials resulted in a lower proportion of patients with antibodies to golimumab than in patients receiving SIMPONI without immunomodulators (12% vs. 26%). There is a trend of decreasing drug concentrations with increasing antibody titers. Although the development of antibodies to golimumab did not preclude clinical response, a trend toward decreased efficacy in ADA positive patients was observed compared to ADA negative patients in the UC trials (clinical response 38% vs. 53%).

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 SIMPONI exposure.

Immune system disorders: Serious systemic hypersensitivity reactions (including anaphylactic reaction) [see WARNINGS AND PRECAUTIONS], sarcoidosis

Neoplasms benign, malignant and unspecified: Melanoma, Merkel cell carcinoma [see WARNINGS AND PRECAUTIONS]

Respiratory, thoracic and mediastinal disorders: Interstitial lung disease

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

Read the entire FDA prescribing information for Simponi (Golimumab Injection)

&Copy; Simponi Patient Information is supplied by Cerner Multum, Inc. and Simponi Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.