DailyMed Label: Tremfya

DailyMed Label: Tremfya

2023

DailyMed Prescription

Tremfya

Guselkumab

Janssen Biotech, Inc.

NDC: 57894-640

NDC: 57894-640

NDC: 57894-640

NDC: 57894-640

NDC: 57894-640

NDC: 57894-640

NDC: 57894-640

NDC: 57894-640

NDC: 57894-640

NDC: 57894-640

NDC: 57894-640

NDC: 57894-640

Guselkumab, an interleukin-23 blocker, is a human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody. Guselkumab is produced in a mammalian cell line using recombinant DNA technology. TREMFYA ® (guselkumab) injection is a sterile, preservative free, clear, colorless to light yellow solution that may contain small translucent particles. TREMFYA is supplied as a single-dose solution in a 1 mL glass syringe with a 27G, half inch fixed needle assembled in a passive needle guard delivery system or One-Press patient-controlled injector for subcutaneous use. Each TREMFYA 1 mL prefilled syringe or One-Press patient-controlled injector contains 100 mg guselkumab, L-histidine (0.6 mg), L-histidine monohydrochloride monohydrate (1.5 mg), polysorbate 80 (0.5 mg), sucrose (79 mg) and water for injection at pH 5.8.

TREMFYA is an interleukin-23 blocker indicated for the treatment of adult patients with: moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy ( 1.1 ) active psoriatic arthritis. ( 1.2 ) TREMFYA is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. TREMFYA is indicated for the treatment of adult patients with active psoriatic arthritis.

Plaque Psoriasis 100 mg administered by subcutaneous injection at Week 0, Week 4 and every 8 weeks thereafter. ( 2.1 ) Psoriatic Arthritis 100 mg administered by subcutaneous injection at Week 0, Week 4 and every 8 weeks thereafter. TREMFYA can be used alone or in combination with a conventional DMARD (e.g., methotrexate). ( 2.2 ) TREMFYA is administered by subcutaneous injection. The recommended dose is 100 mg at Week 0, Week 4, and every 8 weeks thereafter. TREMFYA is administered by subcutaneous injection. The recommended dose is 100 mg at Week 0, Week 4, and every 8 weeks thereafter. TREMFYA may be administered alone or in combination with a conventional disease-modifying antirheumatic drug (cDMARD) (e.g., methotrexate). Administer TREMFYA subcutaneously. Each prefilled syringe or One-Press injector is for single-dose only. Instruct patients to inject the full amount (1 mL), which provides 100 mg of TREMFYA. Do not inject TREMFYA into areas where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis [see Instructions for Use]. TREMFYA is intended for use under the guidance and supervision of a physician. TREMFYA may be administered by a health care professional, or a patient may self-inject after proper training in subcutaneous injection technique. The TREMFYA Instructions for Use contains more detailed patient instructions on the preparation and administration of TREMFYA [see Instructions for Use] . Before injection, remove TREMFYA prefilled syringe or One-Press injector from the refrigerator and allow TREMFYA to reach room temperature (30 minutes) without removing the needle cap. Inspect TREMFYA visually for particulate matter and discoloration prior to administration. TREMFYA is a clear and colorless to light yellow solution that may contain small translucent particles. Do not use if the liquid contains large particles, is discolored or cloudy. TREMFYA does not contain preservatives; therefore, discard any unused product remaining in the prefilled syringe or One-Press injector.

Injection: 100 mg/mL in a single-dose prefilled syringe or single-dose One-Press patient-controlled injector. TREMFYA is a clear and colorless to light yellow solution that may contain small translucent particles. Injection: 100 mg/mL in a single-dose prefilled syringe or single-dose One-Press patient-controlled injector. ( 3 )

TREMFYA is contraindicated in patients with a history of serious hypersensitivity reaction to guselkumab or to any of the excipients [see Warnings and Precautions (5.1) ] . Serious hypersensitivity reactions to guselkumab or to any of the excipients. ( 4 )

Hypersensitivity Reactions : Serious hypersensitivity reactions, including anaphylaxis, may occur. ( 5.1 ) Infections : TREMFYA may increase the risk of infection. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a serious infection develops, discontinue TREMFYA until the infection resolves. ( 5.2 ) Tuberculosis (TB) : Evaluate for TB prior to initiating treatment with TREMFYA. ( 5.3 ) Serious hypersensitivity reactions, including anaphylaxis, have been reported with postmarket use of TREMFYA. Some cases required hospitalization. If a serious hypersensitivity reaction occurs, discontinue TREMFYA and initiate appropriate therapy. TREMFYA may increase the risk of infection. In clinical trials in subjects with plaque psoriasis, infections occurred in 23% of subjects in the TREMFYA group versus 21% of subjects in the placebo group through 16 weeks of treatment. Upper respiratory tract infections, gastroenteritis, tinea infections, and herpes simplex infections occurred more frequently in the TREMFYA group than in the placebo group [see Adverse Reactions (6.1) ] . The rate of serious infections for the TREMFYA group and the placebo group was ≤ 0.2%. A similar risk of infection was seen in placebo-controlled trials in subjects with psoriatic arthritis. Treatment with TREMFYA should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated. In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing TREMFYA. Instruct patients to seek medical help if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, monitor the patient closely and discontinue TREMFYA until the infection resolves. Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TREMFYA. Initiate treatment of latent TB prior to administering TREMFYA. In clinical trials, 105 subjects with plaque psoriasis and 71 subjects with psoriatic arthritis with latent TB who were concurrently treated with TREMFYA and appropriate TB prophylaxis did not develop active TB. Monitor patients for signs and symptoms of active TB during and after TREMFYA treatment. Consider anti-TB therapy prior to initiating TREMFYA in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Do not administer TREMFYA to patients with active TB infection. Prior to initiating therapy with TREMFYA, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with TREMFYA. No data are available on the response to live or inactive vaccines.

The following adverse reactions are discussed in greater detail in other sections of labeling:

The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFα, interferon) during chronic inflammation. Results from an exploratory drug-drug interaction study in subjects with moderate-to-severe plaque psoriasis suggested a low potential for clinically relevant drug interactions for drugs metabolized by CYP3A4, CYP2C9, CYP2C19 and CYP1A2 but the interaction potential cannot be ruled out for drugs metabolized by CYP2D6. However, the results were highly variable because of the limited number of subjects in the study. Upon initiation of TREMFYA in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect or drug concentration and consider dosage adjustment as needed [see Clinical Pharmacology (12.3) ] .

Pregnancy Exposure Registry There is a pregnancy registry that monitors pregnancy outcomes in women exposed to TREMFYA during pregnancy. Patients should be encouraged to enroll in the registry by visiting www.mothertobaby.org/ongoing-study/tremfya-guselkumab, by calling 1-877-311-8972, or emailing MotherToBaby@health.ucsd.edu. Risk Summary There are no available data on TREMFYA use in pregnant women to inform a drug associated risk of adverse developmental outcomes. Human IgG antibodies are known to cross the placental barrier; therefore, TREMFYA may be transmitted from the mother to the developing fetus. In a combined embryofetal development and pre- and post-natal development study, no adverse developmental effects were observed in infants born to pregnant monkeys after subcutaneous administration of guselkumab during organogenesis through parturition at doses up to 30 times the maximum recommended human dose (MRHD). Neonatal deaths were observed at 6- to 30-times the MRHD (see Data ) . The clinical significance of these nonclinical findings is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In a combined embryofetal development and pre- and post-natal development study, pregnant cynomolgus monkeys were administered weekly subcutaneous doses of guselkumab up to 50 mg/kg (30 times the MRHD based on a mg/kg comparison) from the beginning of organogenesis to parturition. Neonatal deaths occurred in the offspring of one control monkey, three monkeys administered guselkumab at 10 mg/kg/week (6 times the MRHD based on a mg/kg comparison) and three monkeys administered guselkumab at 50 mg/kg/week (30 times the MRHD based on a mg/kg comparison). The clinical significance of these findings is unknown. No guselkumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age. Risk Summary There are no data on the presence of guselkumab in human milk, the effects on the breastfed infant, or the effects on milk production. Guselkumab was not detected in the milk of lactating cynomolgus monkeys. Maternal IgG is known to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TREMFYA and any potential adverse effects on the breastfed infant from TREMFYA or from the underlying maternal condition. The safety and efficacy of TREMFYA in pediatric patients (less than 18 years of age) have not been established. Of the 3406 subjects with plaque psoriasis or psoriatic arthritis exposed to TREMFYA, a total of 185 subjects were 65 years or older, and 13 subjects were 75 years or older. No overall differences in safety or effectiveness were observed between older and younger subjects who received TREMFYA. However, the number of subjects aged 65 years and older was not sufficient to determine whether they respond differently from younger subjects [see Clinical Pharmacology (12.3) ] .

TREMFYA ® (guselkumab) Injection is a clear and colorless to light yellow solution that may contain small translucent particles. TREMFYA is supplied as: Single-dose 100 mg/mL prefilled syringe (NDC: 57894-640-01) Single-dose 100 mg/mL One-Press patient-controlled injector (NDC: 57894-640-11) TREMFYA is sterile and preservative-free. Discard any unused portion. Store in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF). Store in original carton until time of use. Protect from light until use. Do not freeze. Do not shake. Not made with natural rubber latex. Keep out of reach of children.

Guselkumab is a human monoclonal IgG1λ antibody that selectively binds to the p19 subunit of interleukin 23 (IL-23) and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Guselkumab inhibits the release of proinflammatory cytokines and chemokines. In evaluated subjects with plaque psoriasis, guselkumab reduced serum levels of IL-17A, IL-17F and IL-22 relative to pre-treatment levels based on exploratory analyses of the pharmacodynamic markers. In evaluated subjects with psoriatic arthritis, serum levels of acute phase proteins C-reactive protein, serum amyloid A and IL-6, and Th17 effector cytokines IL-17A, IL-17F and IL-22 were elevated at baseline. Serum levels of these proteins measured at Week 4 and Week 24 were decreased compared to baseline following guselkumab treatment at Week 0, Week 4 and every 8 weeks thereafter. The relationship between these pharmacodynamic markers and the mechanism(s) by which guselkumab exerts its clinical effects is unknown. Guselkumab exhibited linear pharmacokinetics in healthy subjects and subjects with plaque psoriasis following subcutaneous injections. In subjects with plaque psoriasis, following subcutaneous administration of 100 mg of TREMFYA at Weeks 0 and 4, and every 8 weeks thereafter, mean steady-state trough serum guselkumab concentration was approximately 1.2 mcg/mL. The pharmacokinetics of guselkumab in subjects with psoriatic arthritis was similar to that in subjects with plaque psoriasis. Following subcutaneous administration of 100 mg of TREMFYA at Weeks 0, 4, and every 8 weeks thereafter, mean steady-state trough serum guselkumab concentration was approximately 1.2 mcg/mL. Absorption Following a single 100 mg subcutaneous injection in healthy subjects, guselkumab reached a mean (± SD) maximum serum concentration of 8.09 ± 3.68 mcg/mL by approximately 5.5 days post dose. The absolute bioavailability of guselkumab following a single 100 mg subcutaneous injection was estimated to be approximately 49% in healthy subjects. Distribution In subjects with plaque psoriasis, apparent volume of distribution was 13.5 L. Elimination Apparent clearance in subjects with plaque psoriasis was 0.516 L/day. Mean half-life of guselkumab was approximately 15 to 18 days in subjects with plaque psoriasis across trials. Metabolism The exact pathway through which guselkumab is metabolized has not been characterized. As a human IgG monoclonal antibody, guselkumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. Specific Populations No apparent differences in clearance were observed in subjects ≥ 65 years of age compared to subjects < 65 years of age, suggesting no dose adjustment is needed for elderly subjects. Clearance and volume of distribution of guselkumab increases as body weight increases, however, observed clinical trial data indicate that dose adjustment for body weight is not warranted. No specific trials have been conducted to determine the effect of renal or hepatic impairment on the pharmacokinetics of guselkumab. Drug Interactions Population pharmacokinetic analyses indicated that concomitant use of NSAIDs, oral corticosteroids and conventional DMARDs such as methotrexate, did not affect the clearance of guselkumab. Cytochrome P450 Substrates The effects of guselkumab on the pharmacokinetics of midazolam (metabolized by CYP3A4), warfarin (metabolized by CYP2C9), omeprazole (metabolized by CYP2C19), dextromethorphan (metabolized by CYP2D6), and caffeine (metabolized by CYP1A2) were evaluated in an exploratory study with 6 to 12 evaluable subjects with moderate-to-severe plaque psoriasis. Changes in AUC inf of midazolam, S-warfarin, omeprazole, and caffeine after a single dose of guselkumab were not clinically relevant. For dextromethorphan, changes in AUC inf after guselkumab were not clinically relevant in 9 out of 10 subjects; however, a 2.9-fold change in AUC inf was observed in one individual [ s ee Drug Interactions (7.1) ] .

Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of TREMFYA. No effects on fertility parameters were observed after male guinea pigs were subcutaneously administered guselkumab at a dose of 25 mg/kg twice weekly (15 times the MRHD based on a mg/kg comparison). No effects on fertility parameters were observed after female guinea pigs were subcutaneously administered guselkumab at doses up to 100 mg/kg twice weekly (60 times the MRHD based on a mg/kg comparison).

Four multicenter, randomized, double-blind trials (PsO1 [NCT02207231], PsO2 [NCT02207244], PsO3 [NCT02203032], and PsO4 [NCT02905331]) enrolled subjects 18 years of age and older with moderate-to-severe plaque psoriasis who were eligible for systemic therapy or phototherapy. Subjects had an Investigator's Global Assessment (IGA) score of ≥3 ("moderate") on a 5-point scale of overall disease severity, a Psoriasis Area and Severity Index (PASI) score ≥12, and a minimum affected body surface area (BSA) of 10%. Subjects with guttate, erythrodermic, or pustular psoriasis were excluded. Trials PsO1 and PsO2 In PsO1 and PsO2, 1443 subjects were randomized to either TREMFYA (100 mg at Weeks 0 and 4 and every 8 weeks thereafter) administered with a prefilled syringe, placebo or U.S. licensed adalimumab (80 mg at Week 0 and 40 mg at Week 1, followed by 40 mg every other week thereafter). Both trials assessed the responses at Week 16 compared to placebo for the two co-primary endpoints: the proportion of subjects who achieved an IGA score of 0 ("cleared") or 1 ("minimal"); the proportion of subjects who achieved at least a 90% reduction from baseline in the PASI composite score (PASI 90). Comparisons between TREMFYA and U.S. licensed adalimumab were secondary endpoints at the following time points: at Week 16 (PsO1 and PsO2), the proportions of subjects who achieved an IGA score of 0 or 1, a PASI 90, and a PASI 75 response; at Week 24 (PsO1 and PsO2), and at Week 48 (PsO1), the proportions of subjects achieving an IGA score of 0, an IGA score of 0 or 1, and a PASI 90 response. Other evaluated outcomes included improvement in psoriasis symptoms assessed on the Psoriasis Symptoms and Signs Diary (PSSD) and improvements in psoriasis of the scalp at Week 16. In both trials, subjects were predominantly men and white, with a mean age of 44 years and a mean weight of 90 kg. At baseline, subjects had a median affected BSA of approximately 21%, a median PASI score of 19, and 18% had a history of psoriatic arthritis. Approximately 24% of subjects had an IGA score of severe. In both trials, 23% had received prior biologic systemic therapy. Clinical Response Table 2 presents the efficacy results at Week 16 in PsO1 and PsO2. Table 2: Efficacy Results at Week 16 in Adults with Plaque Psoriasis (NRI NRI = Non-Responder Imputation ) PsO1 PsO2 Endpoint TREMFYA (N=329) n (%) Placebo (N=174) n (%) TREMFYA (N=496) n (%) Placebo (N=248) n (%) IGA response of 0/1 Co-Primary Endpoints ,   IGA response of 0 (cleared) or 1 (minimal) 280 (85) 12 (7) 417 (84) 21 (8) PASI 90 response 241 (73) 5 (3) 347 (70) 6 (2) Table 3 presents the results of an analysis of all the North America sites (i.e., U.S. and Canada), demonstrating superiority of TREMFYA to U.S. licensed adalimumab. Table 3: Efficacy Results in Adults with Plaque Psoriasis (NRI NRI = Non-Responder Imputation ) PsO1 PsO2 Endpoint TREMFYA (N=115) Subjects from sites in the United States and Canada n (%) Adalimumab U.S. licensed adalimumab (N=115) n (%) TREMFYA (N=160) n (%) Adalimumab (N=81) n (%) IGA response of 0/1 (cleared or minimal)   Week 16 97 (84) 70 (61) 119 (74) 50 (62)   Week 24 97 (84) 62 (54) 119 (74) 46 (57)   Week 48 91 (79) 62 (54) NA NA IGA response of 0 (cleared)   Week 24 61 (53) 27 (23) 76 (48) 23 (28)   Week 48 54 (47) 28 (24) NA NA PASI 75 response   Week 16 105 (91) 80 (70) 132 (83) 51 (63) PASI 90 response   Week 16 84 (73) 47 (41) 102 (64) 34 (42)   Week 24 92 (80) 51 (44) 113 (71) 41 (51)   Week 48 84 (73) 53 (46) NA NA An improvement was seen in psoriasis involving the scalp in subjects randomized to TREMFYA compared to placebo at Week 16. Examination of age, gender, race, body weight, and previous treatment with systemic or biologic agents did not identify differences in response to TREMFYA among these subgroups. Maintenance and Durability of Response To evaluate maintenance and durability of response (PsO2), subjects randomized to TREMFYA at Week 0 and who were PASI 90 responders at Week 28 were re-randomized to either continue treatment with TREMFYA every 8 weeks or be withdrawn from therapy (i.e., receive placebo). At Week 48, 89% of subjects who continued on TREMFYA maintained PASI 90 compared to 37% of subjects who were re-randomized to placebo and withdrawn from TREMFYA. For responders at Week 28 who were re-randomized to placebo and withdrawn from TREMFYA, the median time to loss of PASI 90 was approximately 15 weeks. Patient Reported Outcomes Greater improvements in symptoms of psoriasis (itch, pain, stinging, burning and skin tightness) at Week 16 in TREMFYA compared to placebo were observed in both trials based on the Psoriasis Symptoms and Signs Diary (PSSD). Greater proportions of subjects on TREMFYA compared to U.S. licensed adalimumab achieved a PSSD symptom score of 0 (symptom-free) at Week 24 in both trials. Trial PsO3 PsO3 [NCT02203032] evaluated the efficacy of 24 weeks of treatment with TREMFYA in subjects (N=268) who had not achieved an adequate response, defined as IGA ≥2 at Week 16 after initial treatment with U.S. licensed ustekinumab (dosed 45 mg or 90 mg according to the subject's baseline weight at Week 0 and Week 4). These subjects were randomized to either continue with U.S. licensed ustekinumab treatment every 12 weeks or switch to TREMFYA 100 mg at Weeks 16, 20, and every 8 weeks thereafter. Baseline characteristics for randomized subjects were similar to those observed in PsO1 and PsO2. In subjects with an inadequate response (IGA ≥2 at Week 16 to U.S. licensed ustekinumab), greater proportions of subjects on TREMFYA compared to U.S. licensed ustekinumab achieved an IGA score of 0 or 1 with a ≥2 grade improvement at Week 28 (31% vs. 14%, respectively; 12 weeks after randomization). Trial PsO4 PsO4 [NCT02905331] evaluated the efficacy, safety, and pharmacokinetics of TREMFYA administered with the One-Press injector. In this study, 78 subjects were randomized to receive either TREMFYA (100 mg at Weeks 0 and 4 and every 8 weeks thereafter) [N=62], or placebo [N=16]. Baseline characteristics for subjects were comparable to those observed in PsO1 and PsO2. The co-primary endpoints were the same as those for PsO1 and PsO2. Secondary endpoints included the proportion of subjects who achieved an IGA score of 0 at Week 16 and the proportion of subjects who achieved a PASI 100 response at Week 16. A greater proportion of subjects in the guselkumab group achieved an IGA score of 0 or 1 or a PASI 90 response at Week 16 (81% and 76%, respectively) than in the placebo group (0% for both endpoints). The proportion of subjects who achieved an IGA score of 0 at Week 16 was higher in the guselkumab group compared to the placebo group (56% vs. 0%). The proportion of subjects who achieved a PASI 100 response at Week 16 was higher in the guselkumab group compared to the placebo group (50% vs. 0%). The safety and efficacy of TREMFYA were assessed in 1120 subjects in 2 randomized, double-blind, placebo-controlled trials (PsA1 [NCT03162796] and PsA2 [NCT03158285]) in adult subjects with active psoriatic arthritis (PsA) (≥3 swollen joints, ≥3 tender joints, and a C-reactive protein (CRP) level of ≥0.3 mg/dL in PsA1 and ≥5 swollen joints, ≥5 tender joints, and a CRP level of ≥0.6 mg/dL in PsA2) who had inadequate response to standard therapies (e.g., conventional DMARDs [cDMARDs]), apremilast, or nonsteroidal anti-inflammatory drugs [NSAIDs]). Patients in these trials had a diagnosis of PsA for at least 6 months based on the Classification criteria for Psoriatic Arthritis (CASPAR) and a median duration of PsA of 4 years at baseline. In PsA1 approximately 31% of subjects had been previously treated with up to 2 anti-tumor necrosis factor alpha (anti-TNFα) agents whereas in PsA2 all subjects were biologic naïve. Approximately 58% of subjects from both trials had concomitant methotrexate (MTX) use. Patients with different subtypes of PsA were enrolled in both trials, including polyarticular arthritis with the absence of rheumatoid nodules (40%), spondylitis with peripheral arthritis (30%), asymmetric peripheral arthritis (23%), distal interphalangeal involvement (7%) and arthritis mutilans (1%). At baseline, over 65% and 42% of the subjects had enthesitis and dactylitis, respectively and 79% had ≥3% body surface area (BSA) psoriasis skin involvement. PsA1 evaluated 381 subjects who were treated with placebo SC, TREMFYA 100 mg SC at Weeks 0, 4 and every 8 weeks (q8w) thereafter, or TREMFYA 100 mg SC every 4 weeks (q4w). PsA2 evaluated 739 subjects who were treated with placebo SC, TREMFYA 100 mg SC at Weeks 0, 4 and q8w thereafter, or TREMFYA 100 mg SC q4w. The primary endpoint in both trials was the percentage of subjects achieving an ACR20 response at Week 24. Clinical Response In both trials, subjects treated with TREMFYA 100 mg q8w demonstrated a greater clinical response including ACR20, compared to placebo at Week 24 (Tables 4 and 5). Similar responses were seen regardless of prior anti-TNFα exposure in PsA1, and in both trials similar responses were seen regardless of concomitant cDMARD use, previous treatment with cDMARDs, gender and body weight. Table 4: Percent of Subjects with ACR Responses in PsA1 Placebo (N=126) TREMFYA 100 mg q8w (N=127) Response Rate Response Rate Difference from Placebo (95% CI) ACR 20 response Subjects with missing data at a visit were imputed as non-responders at that visit. Subjects who met escape criteria (less than 5% improvement in both tender and swollen joint counts) at Week 16 were allowed to initiate or increase the dose of the permitted concomitant medication and remained on the randomized group. Subjects who initiated or increased the dose of non-biologic DMARD or oral corticosteroids over baseline, discontinued study/study medication or initiated protocol prohibited medications/therapies for PsA prior to a visit were considered non-responders at that visit. Week 16 25% 52% 27 (15, 38) Week 24 22% 52% 30 (19, 41) ACR 50 response Week 16 13% 23% 10 (1, 19) Week 24 9% 30% 21 (12, 31) ACR 70 response Week 16 6% 8% 2 (-4, 8) Week 24 6% 12% 6 (-0.3, 13) Table 5: Percent of Subjects with ACR Responses in PsA2 Placebo (N=246) TREMFYA 100 mg q8w (N=248) Response Rate Response Rate Difference from Placebo (95% CI) ACR 20 response Subjects with missing data at a visit were imputed as non-responders at that visit. Subjects who met escape criteria (less than 5% improvement in both tender and swollen joint counts) at Week 16 were allowed to initiate or increase the dose of the permitted concomitant medication and remained on the randomized group. Subjects who initiated or increased the dose of non-biologic DMARD or oral corticosteroids over baseline, discontinued study/study medication or initiated protocol prohibited medications/therapies for PsA prior to a visit were considered non-responders at that visit. Week 16 34% 55% 22 (13, 30) Week 24 33% 64% 31 (23, 40) ACR 50 response Week 16 9% 29% 19 (13, 26) Week 24 14% 32% 17 (10, 24) ACR 70 response Week 16 1% 14% 13 (9, 17) Week 24 4% 19% 15 (9, 20) The percentage of subjects achieving ACR20 response in PsA2 by visit is shown in Figure 1. Figure 1: Subjects Achieving ACR 20 Response by Visit Through Week 24 in PsA2 The results of the components of the ACR response criteria are shown in Table 6. Table 6: Mean change (SD SD= standard deviation ) from Baseline in ACR Component Scores at Week 16 and 24 based on Observed Data PsA1 PsA2 Placebo (N=126) TREMFYA 100 mg q8w (N=127) Placebo N=246 TREMFYA 100 mg q8w (N=248) No. of Swollen Joints Baseline 10.1 (7.1) 10.9 (9.3) 12.3 (6.9) 11.7 (6.8) Mean change at Week 16 -4.2 (7.0) -7.3 (7.0) -5.8 (7.1) -7.2 (6.0) Mean change at Week 24 -5.1 (6.9) -7.3 (8.0) -6.4 (7.2) -8.1 (6.1) No. of Tender Joints Baseline 19.8 (14.4) 20.2 (14.5) 21.6 (13.1) 19.8 (11.9) Mean change at Week 16 -4.5 (10.8) -10.2 (10.4) -6.8 (10.5) -9.0 (9.4) Mean change at Week 24 -6.8 (13.0) -10.5 (12.0) -7.3 (11.2) -10.4 (9.5) Patient's Assessment of Pain Assessment based on Visual Analog Scale (cm) with the left end indicating "no pain" (for patient's assessment of pain), "very well" (for patient global assessment), or "no arthritis activity" (for physician global assessment) and the right end indicating "the worst possible pain" (for patient assessment of pain), "poor" (for patient global assessment), or "extremely active arthritis (for physician global assessment). Baseline 5.8 (2.2) 6.0 (2.1) 6.3 (1.8) 6.3 (2.0) Mean change at Week 16 -0.8 (2.3) -1.7 (2.4) -0.9 (2.3) -2.2 (2.5) Mean change at Week 24 -0.7 (2.4) -2.2 (2.6) -1.1 (2.4) -2.5 (2.5) Patient Global Assessment Baseline 6.1 (2.2) 6.5 (2.0) 6.5 (1.8) 6.5 (1.9) Mean change at Week 16 -1.0 (2.3) -2.0 (2.6) -1.0 (2.3) -2.3 (2.6) Mean change at Week 24 -0.9 (2.5) -2.5 (2.7) -1.2 (2.6) -2.5 (2.5) Physician Global Assessment Baseline 6.3 (1.7) 6.2 (1.7) 6.7 (1.5) 6.6 (1.6) Mean change at Week 16 -1.9 (2.2) -2.9 (2.4) -2.1 (2.2) -3.5 (2.3) Mean change at Week 24 -2.2 (2.3) -3.5 (2.4) -2.5 (2.3) -3.8 (2.3) Disability Index (HAQ-DI) Disability Index of the Health Assessment Questionnaire; 0 = no difficulty to 3 = inability to perform, measures the patient's ability to perform the following: dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living Baseline 1.2 (0.7) 1.2 (0.6) 1.3 (0.6) 1.3 (0.6) Mean change at Week 16 -0.1 (0.5) -0.3 (0.5) -0.1 (0.5) -0.3 (0.5) Mean change at Week 24 -0.1 (0.5) -0.3 (0.6) -0.2 (0.5) -0.4 (0.5) CRP (mg/dL) Baseline 1.4 (1.9) 1.6 (2.4) 2.1 (2.7) 2.0 (2.4) Mean change at Week 16 -0.2 (1.5) -0.6 (2.2) -0.6 (2.5) -1.0 (2.2) Mean change at Week 24 -0.0 (2.8) -0.7 (2.1) -0.5 (2.5) -1.1 (2.2) Treatment with TREMFYA resulted in an improvement in the skin manifestations of psoriasis in subjects with PsA. Treatment with TREMFYA resulted in improvement in dactylitis and enthesitis in patients with pre-existing dactylitis or enthesitis. Figure 1 Physical Function TREMFYA treated subjects in the TREMFYA 100 mg q8w group in both PsA1 and PsA2 showed greater mean improvement from baseline in physical function compared to subjects treated with placebo as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Weeks 16 and 24. In both studies, the proportion of HAQ-DI responders (≥0.35 improvement in HAQ-DI score) was greater in the TREMFYA q8w dose group compared to placebo at Weeks 16 and 24. Other Health-Related Outcomes General health status was assessed by the Short Form health survey (SF-36). At Week 24, subjects in the TREMFYA 100 mg q8w dose group in both PsA1 and PsA2 showed greater improvement from baseline in the SF-36 physical component summary (PCS) compared with placebo. There was not a statistically significant improvement observed in the SF-36 MCS. At Week 24, there was numerical improvement in the physical functioning, role-physical, bodily-pain, general health, social-functioning and vitality domains but not in the role-emotional and mental health domains. Fatigue was assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue score (FACIT-F) in Studies PsA1 and PsA2. Treatment with TREMFYA resulted in improvement in fatigue as measured by FACIT-F.

Tremfya ® (guselkumab) Injection 100 mg/mL FOR SUBCUTANEOUS USE ONLY Rx only NDC 57894-640-11 Single-dose One-Press patient-controlled injector Discard unused portion Contains no preservative ATTENTION: Dispense the enclosed Medication Guide to each patient PRINCIPAL DISPLAY PANEL - 100 mg/mL Syringe Carton