Liza Takiya

Safety and maintenance of response for tofacitinib monotherapy and combination therapy in rheumatoid arthritis: an analysis of pooled data from open-label long-term extension studies

Objective Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. This post hoc analysis evaluated patients receiving tofacitinib monotherapy or combination therapy, as well as those who switched from monotherapy to combination therapy (mono→combo) or vice versa (combo→mono) in long-term extension (LTE) studies. Methods Data were pooled from open-label LTE studies (ORAL Sequel (NCT00413699; ongoing; data collected 14 January 2016) and NCT00661661) involving patients who participated in qualifying index studies. Efficacy outcomes included American College of Rheumatology 20/50/70 rates, change from baseline in Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4(ESR)), Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index and DAS28-4(ESR) and CDAI low disease activity and remission. Safety was evaluated over 96 months. Results Of the 4967 patients treated, 35.4% initiated tofacitinib monotherapy, 64.6% initiated combination therapy, 2.6% were mono→combo switchers and 7.1% were combo→mono switchers. Patients who switched multiple times were excluded. Of those who initiated monotherapy and combination therapy, 87.8% (1543/1757) and 82.0% (2631/3210), respectively, remained on the same regimen throughout the study; efficacy was maintained. Incidence rates (IRs) for serious adverse events with tofacitinib 5 mg and 10 mg twice daily, respectively, were 9.42 and 8.41 with monotherapy and 8.36 and 10.75 with combination therapy; IRs for discontinuations due to AEs were 7.13 and 6.06 with monotherapy and 7.82 and 8.06 with combination therapy (overlapping CIs). For mono→combo and combo→mono switchers, discontinuations due to AEs were experienced by 0.8% and 0.9%, respectively, within 30 days of switching. Conclusion Tofacitinib efficacy as monotherapy or combination therapy was maintained through month 48 and sustained to month 72, with minimal switching of treatment regimens. Safety was consistent over 96 months. Clinical trial registration NCT00413699 (Pre-results) and NCT00661661 (Results).

THU0193 Reestablishment of efficacy of tofacitinib, an oral janus kinase inhibitor, in rheumatoid arthritis patients after temporary discontinuation

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Objectives To assess the efficacy and safety of tofacitinib after temporary discontinuation and reinitiation of therapy in RA patients (pts). Methods Data were collected from a randomised, parallel-group (grp), controlled, open label, vaccine sub-study in RA pts participating in a long-term extension (LTE) study (NCT00413699). Pts were ≥18 years of age with active RA and had received tofacitinib 10 mg BID for ≥3 months. The sub-study included 2 treatment (tx) grps: “continuous tx” (tofacitinib 10 mg twice daily [BID] as monotherapy or with methotrexate [MTX]) and “interrupted tx” (tofacitinib withdrawn for 2 weeks post-randomisation [Day 1–Day 15; Visits 1–3], then tofacitinib 10 mg BID reinitiated as monotherapy or with MTX at Visit 3); randomisation was stratified by MTX use. Pneumococcal and influenza vaccines were administered to all pts on Day 8 (Visit 2; vaccine titers reported previously1). Blood samples were taken on Days 8, 15 (Visit 3) and 43 (Visit 4). Efficacy endpoints included change from baseline in C-reactive protein (CRP), Health Assessment Questionnaire Disability Index (HAQ-DI) and Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) at each visit. A mixed-effects model with repeated measures was used to evaluate treatment effect at each visit. Analyses for efficacy were exploratory, with no multiplicity adjustment for comparisons. Results Of the 199 pts in this analysis (continuous, n=100; interrupted, n=99), 117 received concomitant MTX. At LTE study baseline (BL) in the continuous and interrupted grps, respectively: 81.8/83.8% of pts were white, 84.8/86.9% were female and mean age was 55.0/53.9 years. BL (Day 1) values for CRP, HAQ-DI and DAS28-4(ESR) were generally similar between groups. At Day 8, mean CRP and DAS28-4(ESR) significantly increased from BL for interrupted vs continuous tx; HAQ-DI values were similar between grps (Figure). As expected at Day 15, mean CRP, HAQ-DI and DAS28-4(ESR) significantly increased from BL for interrupted vs continuous tx. After tofacitinib reinitiation for 28 days (Day 43), changes in CRP, HAQ-DI and DAS28-4(ESR) were similar between grps and approached BL levels. Adverse events (AEs) were experienced by 35.4% and 49.5% of pts receiving interrupted and continuous tx, respectively. The most frequent treatment-emergent AEs were bronchitis and upper respiratory tract infection (each AE: 6 pts) and vaccination-related immunisation reaction, myalgia and rash (each AE: 5 pts). Serious AEs occurred in 3 pts (3%) in each grp. In total, 1 pt (1%), in the interrupted tx grp, discontinued due to a study-drug related AE; no pts discontinued due to disease flare. Conclusions Efficacy of tofacitinib 10 mg BID can be reestablished following loss of efficacy during temporary (2 weeks) tx discontinuation in pts with RA. Pts receiving continuous tx maintained efficacy throughout the study. Further investigations are required. References Winthrop KL et al. Ann Rheum Dis 2016; 75: 687–695. Acknowledgements This study was sponsored by Pfizer Inc. Editorial support was provided by K Haines of CMC and was funded by Pfizer Inc. Disclosure of Interest J. Kaine Speakers bureau: Bristol-Myers Squibb, Pfizer Inc, J. Tesser Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, R. DeMasi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Takiya Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, M. Snyder Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, H. Fan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Wollenhaupt Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc

A pooled analysis of the safety of tofacitinib as monotherapy or in combination with background conventional synthetic disease-modifying antirheumatic drugs in a Phase 3 rheumatoid arthritis population

OBJECTIVE This post-hoc, pooled analysis of Phase 3 studies of tofacitinib examined the safety of tofacitinib 5 and 10 mg twice daily (BID) when used as monotherapy versus combination therapy with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with rheumatoid arthritis (RA). METHODS Pooled data from six double-blind, randomized controlled Phase 3 studies of tofacitinib 5 and 10 mg BID in patients with RA were analyzed for safety and stratified by administration as monotherapy (ORAL Solo: NCT00814307 and ORAL Start: NCT01039688) or in combination with csDMARDs (ORAL Sync: NCT00856544, ORAL Standard: NCT00853385, ORAL Scan: NCT00847613, and ORAL Step: NCT00960440), and by glucocorticoid use at baseline. Safety assessments included incidence rates (IRs) for serious adverse events (SAEs), discontinuations due to AEs, serious infection events, and herpes zoster (HZ), and were evaluated throughout the duration of the Phase 3 studies. RESULTS In total, 3881 patients were included in the safety analysis (monotherapy studies: n = 1380; combination therapy studies: n = 2501). IRs for selected AEs of interest were generally numerically lower in patients who received tofacitinib 5 and 10 mg BID as monotherapy than as combination therapy (SAEs: IR [range] 6.21-6.72 versus IR 10.17-13.46; discontinuations due to AEs: IR 5.53-6.18 versus IR 10.80-11.01; serious infections: IR 1.57-1.66 versus IR 3.39-3.56; HZ: IR 1.95-2.93 versus IR 4.37-4.99, respectively), irrespective of tofacitinib dose or glucocorticoid use. There were too few patients and events within the placebo group to fully evaluate effect between combination therapy and monotherapy. CONCLUSIONS Safety profiles were generally similar between patients receiving monotherapy and combination therapy; however, selected safety events of interest, including HZ and serious infections, showed lower IRs with non-overlapping 95% confidence intervals for tofacitinib all monotherapy versus combination therapy. Tofacitinib monotherapy may, therefore, have fewer safety events compared with combination therapy, and have a favorable risk-benefit profile in patients with active RA who are intolerant to csDMARDs.

SAT0247 Impact of glucocorticoids on efficacy and safety of tofacitinib with and without methotrexate and adalimumab with methotrexate for rheumatoid arthritis: results from a phase 3b/4 randomised trial

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Glucocorticoids (GC) are an established therapy in RA that are often used to rapidly reduce pain and inflammation while awaiting the effects of disease-modifying antirheumatic drugs. Objectives: A post hoc analysis to describe the impact of background GC on the efficacy and safety of tofacitinib with and without methotrexate (MTX) and adalimumab (ADA) with MTX in ORAL Strategy. Methods: ORAL Strategy (NCT02187055) was a 1-year, double-blind, Phase 3b/4, head-to-head, non-inferiority randomised controlled trial in adult patients (pts) with active RA despite MTX therapy. Pts were randomised 1:1:1 to receive tofacitinib 5 mg twice daily (BID; tofa mono), tofacitinib 5 mg BID + MTX (tofa+MTX) or subcutaneous ADA 40 mg every other week + MTX (ADA+MTX). Pts receiving low-dose GC (≤10 mg/day prednisone or equivalent) before enrolment maintained a stable dose throughout the study period. The following efficacy endpoints were assessed through Month 12 for pts receiving tofa mono, tofa+MTX and ADA+MTX with/without GC: ACR20, ACR50 and ACR70 response rates, proportions of patients achieving low disease activity (LDA; DAS28–4[ESR]≤3.2) and remission (DAS28–4[ESR]<2.6) and change from baseline (BL) in HAQ-DI (ΔHAQ-DI). Safety endpoints were evaluated throughout the study and included adverse events (AEs), serious AEs (SAEs), discontinuations due to AEs and serious infection events (SIEs). Results: 1146 patients were randomised and treated; low-dose BL GC were received by 228/384 (59.4%) pts receiving tofa mono (mean [SD] BL GC dose: 7.5 [13.7] mg/day), 215/376 (57.2%) pts receiving tofa+MTX (mean [SD] BL GC dose: 6.5 [2.5] mg/day) and 223/386 (57.8%) pts receiving ADA+MTX (mean [SD] BL GC dose: 6.4 [2.6] mg/day). BL demographics and disease characteristics were generally similar across treatment groups, regardless of BL GC use. Efficacy endpoints (ACR50 response rate, LDA and remission rates, ΔHAQ-DI) were generally similar for each treatment group when stratified by GC use (figure 1, table 1; similar results were seen for ACR20/70 response rates – data not shown). GC use did not appear to be associated with higher rates of AEs, discontinuations due to AEs, SIEs and SAEs; some AE rates were higher with MTX than without MTX (table 2). SIEs in pts using GC included herpes zoster (HZ; tofa mono, n=2) and tuberculous meningitis (tofa+MTX, n=1); in pts not using GC, there was 1 event each of cytomegalovirus chorioretinitis (tofa+MTX), pulmonary TB (tofa+MTX), HZ (ADA+MTX) and varicella (ADA+MTX).Figure 1 Proportion of patients achieving ACR50 response according to treatment group and GC use (FAS, with imputation*)Table 1 Response rates in patients over 12 months, with or without baseline GC (FAS)Table 2 Summary of AEs, discontinuations due to AEs, SAEs and SIEs over 12 months Conclusions: In pts with RA, concomitant stable GC use did not appear to impact the efficacy of tofacitinib 5 mg BID±MTX or ADA+MTX. The finding that GC use was not associated with higher AE rates was unexpected and of interest. Acknowledgements: Study sponsored by Pfizer Inc. Medical writing support was provided by C Viegelmann of CMC and funded by Pfizer Inc. Disclosure of Interest: R. Fleischmann Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celltrion, Eli Lilly, Genentech, GSK, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celltrion, Eli Lilly, Genentech, GSK, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, J. Wollenhaupt Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, S. Cohen Grant/research support from: AbbVie, Amgen, Astellas, Bristol-Meyers Squibb, Eli Lilly, Genentech, Gilead, Janssen, Novartis, Pfizer Inc, Roche, Sandoz, Consultant for: AbbVie, Amgen, Astellas, Bristol-Meyers Squibb, Eli Lilly, Genentech, Gilead, Janssen, Novartis, Pfizer Inc, Roche, Sandoz, J. Smolen Grant/research support from: AbbVie, Eli Lilly, Janssen, MSD, Pfizer Inc, Roche, Consultant for: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celltrion, Eli Lilly, GSK, ILTOO, Janssen, MedImmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celltrion, Eli Lilly, GSK, ILTOO, Janssen, MedImmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, P. Dahl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, N. Iikuni Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, H. Shi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Tatulych Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Takiya Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

OP0037 Efficacy of tofacitinib after temporary discontinuation in patients with rheumatoid arthritis: analysis of data from open-label long-term extension studies

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Given the chronic nature of RA, there may be situations when therapy is temporarily discontinued. It is important to understand loss of response during temporary discontinuation and the ability to regain disease control following treatment reinitiation. Re-establishment of tofacitinib efficacy following temporary discontinuation/reinitiation has been previously demonstrated in patients (pts) with RA participating in the vaccine sub-study of the long-term extension (LTE) study ORAL Sequel.1 Objectives To further assess tofacitinib efficacy and safety after temporary discontinuation and reinitiation in pts with RA in LTE studies. Methods Data were pooled from two open-label LTE studies (NCT00413699 [database lock: March 2017] and NCT00661661) of pts with RA who had completed qualifying Phase 1/2/3 index studies. Pts received tofacitinib 5 or 10 mg twice daily as monotherapy or with conventional synthetic disease-modifying antirheumatic drugs. Pts who received continuous tofacitinib for ≥4 months, temporarily discontinued tofacitinib for 14–30 days and then resumed treatment were included in the analysis. Efficacy outcomes were analysed at the pre-interruption visit (≤90 days before discontinuation) and at the post-interruption visit (within 14–42 days of resuming treatment); data from the interruption period were not analysed. Efficacy outcomes included: ACR20/50/70 response rates, mean tender and swollen joint counts, mean C-reactive protein levels and mean DAS28–4(ESR), CDAI, HAQ-DI, Patient Global Assessment of arthritis, Pain and Physician Global Assessment of arthritis scores. Safety was analysed from Day 1 of temporary discontinuation to the post-interruption visit and included adverse events (AEs), serious AEs (SAEs) and discontinuations due to AEs that occurred within the time range. Results 261 pts met the criteria for temporary discontinuation. Median (range) duration of temporary discontinuation was 1914–30 days. Pt demographics are shown in table 1. Efficacy outcomes were generally similar at pre- and post-interruption visits (table 2). From Day 1 of discontinuation to the post-interruption visit, AEs, SAEs and discontinuations due to AEs occurred in 142 (54.4%), 29 (11.1%) and 4 (1.5%) pts, respectively.Abstract OP0037 – Table 1 Patients demographics and baseline disease characteristics1 Abstract OP0037 – Table 2 Efficacy endpoints at the pre-interruption visit (≤90 days before temporary discontinuation) and post-interruption visit (within 14–42 days of resuming treatment) Conclusions In pts with RA who temporarily discontinued tofacitinib, similar efficacy responses were observed at pre– and post–interruption visits, suggesting that there is no loss of efficacy after temporary withdrawal and reinitiation of tofacitinib. The safety profile was consistent with previous tofacitinib reports in LTE studies over 9 years.2 References [1] Kaine J, et al. Arthritis Rheumatol2017;69(suppl 10):Abstract 424. [2] Wollenhaupt J, et al. Arthritis Rheumatol2017;69(suppl 10):Abstract 522. Acknowledgements Study sponsored by Pfizer Inc. Medical writing support was provided by AG McCluskey of CMC and funded by Pfizer Inc. Disclosure of Interest J. Kaine Speakers bureau: Bristol-Myers Squibb, Pfizer Inc, J. Tesser Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, R. DeMasi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Takiya Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, M. Snyder Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, H. Fan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, V. Bandi Consultant for: Pfizer Inc through Eliassen Group Inc, J. Wollenhaupt Speakers bureau: Pfizer Inc

THU0202 Clinical Outcomes of Rheumatoid Arthritis Patients Receiving Tofacitinib Monotherapy in The Open-Label Long-Term Extension

Background Treatment options delivering sustained efficacy when given as monotherapy in RA are limited.1 Tofacitinib is an oral JAK inhibitor for the treatment of RA. Tofacitinib monotherapy demonstrated efficacy in adult patients (pts) with RA in two Phase (P) 3 index studies (ORAL Solo2 and ORAL Start3). Objectives To present data through Month 84 for safety and Month 60 for efficacy for pts who stayed on tofacitinib monotherapy in long-term extension (LTE) studies. Methods Data were pooled from two tofacitinib LTE studies (NCT00413699 [ongoing; database unlocked as of Mar 2015 data cut-off] and NCT00661661 [completed; Apr 2014]). Pts from P 1/2/3 tofacitinib index studies received tofacitinib 5 or 10 mg twice daily (BID) as monotherapy or with background conventional synthetic DMARDs in LTE. For tofacitinib and permitted concomitant RA medications, dose adjustments were allowed for inadequate efficacy or for safety reasons. In this analysis, pts were assigned to tofacitinib 5 or 10 mg BID groups based on average total daily dose in LTE (<15 mg/day or ≥15 mg/day, respectively). Monotherapy was defined as those pts who received tofacitinib without other DMARDs throughout the LTE. Baseline values were those of the index studies for pts enrolling in LTE within 14 days of index study; for all others, baseline was start of LTE. Safety was evaluated through Month 84 and efficacy through Month 60 due to limited sample size. Results 1750 pts initiated LTE on tofacitinib monotherapy; 1552 (89%) stayed on monotherapy throughout LTE (495 on 5 mg BID; 1057 on 10 mg BID). For pts staying on monotherapy, mean (max) treatment duration was 1248 (2892) and 1011 (2377) days for 5 and 10 mg BID, respectively. Efficacy responses for tofacitinib monotherapy were stable through Month 60 (Table 1). In the 5 and 10 mg groups, 66% and 82% of pts, respectively, stayed on initial dose throughout LTE. The proportion of pts staying on steroids decreased from 56% to 40% and 41% to 35%, in the 5 and 10 mg groups respectively, from baseline to Month 60. Rates of discontinuation due to lack of efficacy and adverse events (AEs), and of serious infection and malignancy (excluding non-melanoma skin cancer) were low (Table 1). Conclusions In this analysis of pts receiving tofacitinib monotherapy in the LTE studies, nearly 90% of pts stayed on monotherapy, most did not have tofacitinib dose adjustments or add a DMARD and efficacy was sustained over 60 months, with low rates of discontinuation due to lack of efficacy or AEs. Safety was consistent with what has been reported previously. References Smolen JS et al. Ann Rheum Dis 2014; 73: 492–509. Fleischmann R et al. N Engl J Med 2012; 367: 495–507. Lee EB et al. N Engl J Med 2014; 370: 2377–2386. Acknowledgement Previously presented (Fleischmann R et al. Arthritis Rheumatol. 2015; 67 (S10): Abstr 1639) and reproduced with permission from Arthritis Rheumatol. This study was funded by Pfizer Inc. Editorial support was provided by S Johnson, PhD, of Complete Medical Communications and funded by Pfizer Inc. Disclosure of Interest R. Fleischmann Grant/research support from: Pfizer Inc, J. Wollenhaupt Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, L. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. Maniccia Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Takiya Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. van Vollenhoven Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc

THU0200 Effect of Methotrexate Dose on The Efficacy of Tofacitinib: Treatment Outcomes from A Phase 3 Clinical Trial of Patients with Rheumatoid Arthritis

Background Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). ORAL Scan was a 2-year, randomised, Phase 3, clinical trial that evaluated tofacitinib therapy with background methotrexate (MTX) in patients (pts) with RA and an inadequate response (IR) to MTX.1 Objectives To study the effect of MTX dose on tofacitinib efficacy in pts from the ORAL Scan study. Methods In ORAL Scan, MTX-IR pts with RA were randomised 4:4:1:1 to tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, or placebo with advancement to 5 mg BID or to 10 mg BID at Month (Mo) 3 or Mo 6, in combination with background MTX. MTX dose was stable throughout the study and was categorised as Low (≤12.5 mg/week), Medium (>12.5 to <17.5 mg/week), or High (≥17.5 mg/week). Endpoints evaluated at Mo 6 included ACR response rates, proportion of pts achieving low disease activity measured by Clinical Disease Activity Index (CDAI ≤10), CDAI defined remission rate (CDAI ≤2.8), proportion of pts achieving an improvement ≥0.5 in Health Assessment Questionnaire-Disability Index (HAQ-DI), and least squares mean change from baseline in HAQ-DI, Disease Activity Score (DAS28-4[ESR]) and CDAI. Binary variables were evaluated with non-responder imputation, and continuous variables were analysed using a longitudinal model. Regression analyses were conducted to evaluate efficacy responses by MTX dose group and other covariates. Results 797 pts were randomised and treated (tofacitinib 5 mg BID, n=321; tofacitinib 10 mg BID, n=316; placebo, n=160). In total, 242 pts were included in the Low MTX (9 mg mean) dose group, 333 in the Medium MTX (15 mg mean) dose group, and 222 in the High MTX (21 mg mean) dose group. Baseline demographics and disease characteristics were generally similar across MTX dose groups, though weight, BMI, glucocorticoid (GC) use and CDAI were higher in the High MTX dose group. At Mo 6, greater efficacy was seen with tofacitinib compared with placebo for all endpoints across the 3 MTX dose groups (Table). Efficacy for placebo-treated pts was generally numerically greater in the Medium and High MTX dose groups than in the Low MTX dose group. Efficacy with tofacitinib appeared similar regardless of MTX dose group. Regression analyses demonstrated a lack of effect of BMI, GC use and MTX dose groups on efficacy assessments. Conclusions In this post-hoc analysis, clinical efficacy of tofacitinib at Mo 6 was greater than placebo, and appeared similar regardless of MTX dose, as in these pts, tofacitinib was added to patients that had an inadequate response to MTX. Higher MTX doses did not appear to result in additional efficacy to tofacitinib than lower doses. A randomised clinical trial is needed in which different doses of MTX are added to tofacitinib in MTX-naïve pts in order to examine the effect of MTX dose on tofacitinib efficacy. References van der Heijde D et al. Arthritis Rheumatol 2013; 65: 559–570. Acknowledgement Previously presented (Fleischmann R et al. Arthritis Rheumatol 2015; 67 (S10): Abstr 1640) and reproduced with permission from Arthritis Rheumatol. This study was funded by Pfizer Inc. Editorial support was provided by S Johnson of CMC, and funded by Pfizer Inc. Disclosure of Interest R. Fleischmann Grant/research support from: Pfizer Inc, AbbVie, Consultant for: Pfizer Inc, AbbVie, P. Mease Grant/research support from: Pfizer Inc, Speakers bureau: Pfizer Inc, S. Schwartzman Consultant for: Pfizer Inc, L.-J. Hwang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Soma Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Connell Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Takiya Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, E. Bananis: None declared

THU0132 Comparative Effectiveness of TNFI and Tofacitinib Monotherapy in Clinical Practice: Results from Corrona Registry: Table 1.

Background TNF inhibitors (TNFi) can be used as monotherapy (mono) or in combination (combo) with conventional DMARDS (cDMARDS). Clinical trial data and European registry data have shown evidence of better effectiveness of TNFi combo therapy than mono. Effectiveness of mono vs combo in US clinical practice, in particular among biologic naïve and experienced patients, has not been assessed. Objectives This study was carried out to quantify the prevalence and effectiveness of TNFi monotherapy use in US clinical practice. A secondary objective was to contrast this with tofacitinib (tofa) monotherapy use and effectiveness. Methods RA patients initiating a TNFi (adalimumab, etanercept, infliximab, golimumab, certolizumab pegol) or tofa with a six month follow-up in Corrona US were identified. A subcohort of TNFi initiations after 11/6/2012 (market approval of tofa) were used for comparisons with tofa initiators. We defined combo therapy as TNFi or tofa used with MTX alone and mono as no use of any cDMARD. The primary outcome was achieving low disease activity (LDA) or remission based on CDAI (≤10) at 6 months. Patients switching to another biologic prior to 6 months were defined as non-responders. Secondary outcomes included modified ACR20/50/70 and mean change in CDAI. Combo and mono initiators were matched within line of therapy using a propensity score. Covariates for the model were selected if the standardized mean difference between the groups >0.1. Results There were 7076 TNFi initiations in Corrona, with 2091 (30%) mono initiations. Mono by line of therapy was 21%, 35% and 41% for 2nd, 3rd and 4th line therapy, respectively. There were 325 tofa initiations with 201 (61%) mono and mono rates of 50%, 65% and 63% for 2nd, 3rd and 4th line therapy, respectively. In the matched populations, across outcome measures (Table 1), TNFi combo was more effective than TNFi mono in 2nd line therapy (55.6% LDA vs 47.1% LDA) and similar in 3rd and 4th line therapy. Tofa combo therapy was similar to mono in the matched populations (35.4% LDA vs 32.3% LDA). Tofa mono was similar to TNFi combo therapy in the matched populations (33.3% LDA vs 33.3% LDA).Table 1. Matched patients TNFi Combo vs TNFi Mono Tofa Combo vs Tofa Mono TNFi Combo vs Tofa Mono 2nd line* (n=1130) 3rd line (n=1044) 4th line (n=680) 3rd & 4th line (n=130) 3rd and 4th line (n=186) LDA OR [95% CI] 1.4 [1.1–1.8] 1.1 [0.9–1.5] 0.7 [0.5–1.0] 1.2 [0.5–2.5] 1.0 [0.4–1.8] mACR20 OR [95% CI] 1.6 [1.2–2.1] 1.2 [0.9–1.5] 1.2 [0.8–1.8] 0.6 [0.3–1.6] 0.9 [0.5–1.8] ΔCDAI meanΔ [95% CI] −2.0 [−3.4–0.6] −0.9 [−2.5–0.6] −2.1 [−4.1–0.1] 0.2 [−4.8–5.2] −1.6 [−4.8–1.7] *2nd line was defined as prior use of at least one cDMARD and no prior use of any biologic. Conclusions TNFi monotherapy is common in U.S. clinical practice. TNFi monotherapy is less effective than combination therapy especially in biologic naïve patients. There is no evidence that tofa monotherapy is less effective than tofa combination therapy or TNFi combination therapy. Acknowledgement This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, BMS, Crescendo, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Disclosure of Interest G. Reed Shareholder of: Corrona, LLC, Employee of: Corrona, LLC, R. Gerber Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., Y. Shan Employee of: Corrona, LLC, L. Takiya Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., K. Dandreo Employee of: Corrona, LLC, D. Gruben Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., J. Kremer Shareholder of: Corrona, LLC, Consultant for: AbbVie, Amgen, BMS, Genentech, GSK, Lilly, Medimmune, Pfizer, Sanofi, Employee of: Corrona, LLC, Speakers bureau: Genentech (for non-branded talk only), G. Wallenstein Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc.