ks 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. 5.3 pre-treatment evaluation for tuberculosis 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. 5.4 immunizations 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.

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] . 2.4 preparation for use of tremfya prefilled syringe or one-press injector 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.

subjects with moderate-to-severe plaque psoriasis received tremfya. of these, 1393 subjects were exposed to tremfya for at least 6 months and 728 subjects were exposed for at least 1 year. data from two placebo- and active-controlled trials (pso1 and pso2) in 1441 subjects (mean age 44 years; 70% males; 82% white) were pooled to evaluate the safety of tremfya (100 mg administered subcutaneously at weeks 0 and 4, followed by every 8 weeks). weeks 0 to 16: in the 16-week placebo-controlled period of the pooled clinical trials (pso1 and pso2), adverse events occurred in 49% of subjects in the tremfya group compared to 47% of subjects in the placebo group and 49% of subjects in the u.s. licensed adalimumab group. serious adverse events occurred in 1.9% of subjects in the tremfya group (6.3 events per 100 subject-years of follow-up) compared to 1.4% of subjects in the placebo group (4.7 events per 100 subject-years of follow-up), and in 2.6% of subjects in u.s. licensed adalimumab group (9.9 events per 100 subject-years of follow-up). table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the tremfya group than in the placebo group during the 16-week placebo-controlled period. table 1: adverse reactions occurring in ≥1% of subjects through week 16 in pso1 and pso2 tremfya subjects receiving 100 mg of tremfya at week 0, week 4, and every 8 weeks thereafter 100 mg n=823 n (%) adalimumab u.s. licensed adalimumab n=196 n (%) placebo n=422 n (%) upper respiratory infections upper respiratory infections include nasopharyngitis, upper respiratory tract infection (urti), pharyngitis, and viral urti. 118 (14.3) 21 (10.7) 54 (12.8) headache headache includes headache and tension headache. 38 (4.6) 2 (1.0) 14 (3.3) injection site reactions injection site reactions include injection site erythema, bruising, hematoma, hemorrhage, swelling, edema, pruritus, pain, discoloration, induration, inflammation, and urticaria. 37 (4.5) 15 (7.7) 12 (2.8) arthralgia 22 (2.7) 4 (2.0) 9 (2.1) diarrhea 13 (1.6) 3 (1.5) 4 (0.9) gastroenteritis gastroenteritis includes gastroenteritis and viral gastroenteritis. 11 (1.3) 4 (2.0) 4 (0.9) tinea infections tinea infections include tinea pedis, tinea cruris, tinea infection, and tinea manuum infections. 9 (1.1) 0 0 herpes simplex infections herpes simplex infections include oral herpes, herpes simplex, genital herpes, genital herpes simplex, and nasal herpes simplex. 9 (1.1) 0 2 (0.5) adverse reactions that occurred in < 1% but > 0.1% of subjects in the tremfya group and at a higher rate than in the placebo group through week 16 in pso1 and pso2 were migraine, candida infections, and urticaria. specific adverse reactions infections infections occurred in 23% of subjects in the tremfya group compared to 21% of subjects in the placebo group. the most common (≥ 1%) infections were upper respiratory infections, gastroenteritis, tinea infections, and herpes simplex infections; all cases were mild to moderate in severity and did not lead to discontinuation of tremfya. elevated liver enzymes elevated liver enzymes were reported more frequently in the tremfya group (2.6%) than in the placebo group (1.9%). of the 21 subjects who were reported to have elevated liver enzymes in the tremfya group, all events except one were mild to moderate in severity and none of the events led to discontinuation of tremfya. safety through week 48 through week 48, no new adverse reactions were identified with tremfya use and the frequency of the adverse reactions was similar to the safety profile observed during the first 16 weeks of treatment. psoriatic arthritis tremfya was studied in two placebo-controlled trials in subjects with psoriatic arthritis (748 subjects on tremfya and 372 subjects on placebo). of the 748 subjects who received tremfya, 375 subjects received tremfya 100 mg at week 0, week 4, and every 8 weeks thereafter and 373 subjects received tremfya 100 mg every 4 weeks. the overall safety profile observed in subjects with psoriatic arthritis treated with tremfya is generally consistent with the safety profile in subjects with plaque psoriasis with the addition of bronchitis and neutrophil count decreased. in the 24-week placebo-controlled period, combined across the two studies, bronchitis occurred in 1.6% of subjects in the tremfya q8w group and 2.9% of subjects in the tremfya q4w group compared to 1.1% of subjects in the placebo group. neutrophil count decreased occurred in 0.3% of subjects in the tremfya q8w and 1.6% of subjects in the tremfya q4w group compared to 0% of subjects in the placebo group. the majority of events of neutrophil count decreased were mild, transient, not associated with infection and did not lead to discontinuation. 6.2 immunogenicity as with all therapeutic proteins, there is the potential for immunogenicity with tremfya. 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 incidence of antibodies to guselkumab across indications or with the incidences of antibodies to other products may be misleading. plaque psoriasis up to week 52, approximately 6% of subjects treated with tremfya developed antidrug antibodies. of the subjects who developed antidrug antibodies, approximately 7% had antibodies that were classified as neutralizing antibodies. among the 46 subjects who developed antibodies to guselkumab and had evaluable data, 21 subjects exhibited lower trough levels of guselkumab, including one subject who experienced loss of efficacy after developing high antibody titers. up to week 156, approximately 9% of subjects treated with tremfya developed antidrug antibodies and of these subjects approximately 6% were classified as neutralizing antibodies. however, antibodies to guselkumab were generally not associated with changes in clinical response or development of injection-site reactions. psoriatic arthritis up to week 24, 2% (n=15) of subjects treated with tremfya developed antidrug antibodies. of these subjects, 1 had antibodies that were classified as neutralizing antibodies. overall, the small number of subjects who were positive for antibodies to guselkumab limits definitive conclusion of the effect of immunogenicity on the pharmacokinetics, efficacy and safety of guselkumab. 6.3 postmarketing experience the following adverse reactions have been reported during post-approval of tremfya. 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 tremfya exposure. immune system disorders: hypersensitivity, including anaphylaxis [see warnings and precautions (5.1) ] skin and subcutaneous tissue disorders: rash [see warnings and precautions (5.1) ]

nancies 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. 8.2 lactation 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. 8.4 pediatric use the safety and efficacy of tremfya in pediatric patients (less than 18 years of age) have not been established. 8.5 geriatric use 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) ] .

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.

thereafter. the relationship between these pharmacodynamic markers and the mechanism(s) by which guselkumab exerts its clinical effects is unknown. 12.3 pharmacokinetics 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) ] .

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) ] .

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%). 14.2 psoriatic arthritis 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.

lf-administering to inject the full dose of tremfya [see medication guide and instructions for use] . instruct patients or caregivers in the technique of proper needle and syringe disposal. needles and syringes should be disposed of in a puncture-resistant container. advise patients and caregivers not to reuse needles or syringes. remind patients if they forget to take their dose of tremfya to inject their dose as soon as they remember. they should then take their next dose at the appropriate scheduled time.