Initiation Of Tofacitinib Research Articles

Tofacitinib for child-onset systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can cause diverse clinical manifestations in multiple organ systems. Child-onset SLE (cSLE) is associated with significantly higher morbidity and mortality than adult-onset SLE. The traditional treatments for SLE (glucocorticoids, antimalarials, conventional and biological disease-modifying antirheumatic drugs) often have significant adverse effects and may not fully control disease activity. Tofacitinib is an oral Janus kinase (JAK) inhibitor that inhibits the JAK-STAT pathway and has the potential to reduce SLE severity. cSLE patients who received tofacitinib and had at least one follow-up visit were retrospectively examined. Case histories, laboratory test results, and treatment regimens were analyzed at disease onset, initiation of tofacitinib treatment, and 1, 3, 6, 9, 12, 18, and 24 months after starting tofacitinib. We examined 9 patients with refractory cSLE. All patients were female and the average age at diagnosis was 10.67 years. At initiation of tofacitinib, the average age was 13.28 years and the average disease duration was 2.62 years. Four patients experienced alleviation of symptoms and reduced their daily prednisone dosages; one of them also discontinued cyclosporine A and two of them also discontinued belimumab. The other 5 patients experienced no apparent benefit. Tofacitinib may provide clinical benefits for some patients with refractory cSLE, and can also allow reduction in the glucocorticoid dosage. Tofacitinib has the potential as an adjunctive treatment for some patients with cSLE.

Biomarker Changes in Response to Tofacitinib Treatment in Patients with Polyarticular Course Juvenile Idiopathic Arthritis.

Examine levels of candidate blood-based biomarkers (CBB) in juvenile idiopathic arthritis (JIA) treated with tofacitinib. JIA patients who participated in clinical trial NCT02592434 received tofacitinib from baseline to week 18. Serial serum samples were assayed for CBB (S100A8/9, S100A12, IL-18, SAA, resistin, VEGF, Angiopoietin-1, Angiopoietin-2, MMP8, MMP2, TIMP1, Leptin, CXCL9, sIL2R, ICAM-1, sTNFr, IL-6, IL-23, MCP1, CCL18, and CCL20). Association of CBB with JIA response to treatment from baseline to week 18 were assessed. This study included 166 patients with polyarticular-course JIA. Paired serum samples from 143 patients were available at both baseline and week 18. There were 35% (50/143) of patients with a JIA-American College of Rheumatology 90 (JIA-ACR90) level improvement while 90/121/137 (63%/85%/96%) achieved JIA-ACR70/50/30 improvement at wk18. Despite small numerical differences by JIA category, there were no baseline CBB values that independently predicted a decrease in JADAS-27 or JIA-ACR90 response by week 18. Decrease in resistin level (baseline to week 18) was significantly associated with wk18 improvement in JADAS-27 and JIA-ACR90 response, after adjusting for age, sex, JIA disease duration and baseline resistin [(r2 0.79, SE, 0.070, p<0.01 and OR(95%CI) = 1.134(1.018,1.264)]. HLA-B27 positivity was significantly associated with not achieving a JIA-ACR90 response at week 18 (p=0.0097). Among the CBB included, only resistin was significantly associated with treatment response, and no CBB was identified that forecasts JIA improvement after initiation of tofacitinib. The association of HLA-B27 positivity with lower response to tofacitinib in JIA is intriguing and merits further study.

Long-term efficacy and safety of tofacitinib in patients with ulcerative colitis: 3-year results from a real-world study.

The efficacy and safety of tofacitinib for the treatment of refractory ulcerative colitis (UC) has been demonstrated in clinical trials. Although, a series of reports with real-world evidence of its short-term efficacy and safety profiles have already been published, reports of long-term real-world data have been limited. We aimed to show our 3-year evidence on the clinical use of tofacitinib for the treatment of UC, focusing on its efficacy and safety profiles. A retrospective observational study was conducted on patients who started tofacitinib for active refractory UC at our hospital. The primary outcome was the retention rate until 156 weeks after initiating tofacitinib. The secondary outcomes were short-term efficacy at 4, 8, and 12 weeks; long-term efficacy at 52, 104, and 156 weeks; prognostic factors related to the cumulative retention rate; loss of response; and safety profile, including adverse events. Forty-six patients who were able to be monitored for up to 156 weeks after tofacitinib initiation, were enrolled in this study. Continuation of tofacitinib was possible until 156 weeks in 54.3%, with > 50% response rates and > 40% remission rates. Among patients in whom response or remission was achieved and tofacitinib was deescalated after 8 weeks of induction treatment, 54.3% experienced relapse but were successfully rescued by and retained on reinduction treatment, except for 1 patient. No serious AEs were observed in the study. Tofacitinib is effective and safe as long-term treatment in a refractory cohort of UC patients in real-world clinical practice.

Safety and efficacy of tofacitinib for the treatment of patients with juvenile idiopathic arthritis: preliminary results of an open-label, long-term extension study

ObjectivesWe report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study.MethodsPatients (2–<18 years) with JIA who completed phase...

Colombian experience with the use of tofacitinib in severe acute ulcerative colitis: A case series study

IntroductionTofacitinib is indicated in patients with moderate to severe ulcerative colitis (UC); however, given its rapid onset of action, it may constitute an alternative in patients with hospitalized severe acute UC. There are few data on this indication in the literature. The aim of this study was to describe the efficacy and safety of tofacitinib in the management of patients with hospitalized UC, as well as its clinical characteristics and other treatment patterns. Materials and methodsDescriptive observational study of adults and children with CUAG treated with tofacitinib between June 2019 and December 2022 in Colombia. Sociodemographic and clinical variables were collected, therapeutic response was evaluated in different periods of time and descriptive analysis of quantitative and qualitative variables was performed. ResultsSix patients (five adults and one pediatric), mean age 33.2 (SD: 8.5) years, with CUAG. Symptom remission was obtained in 100% of patients at day 7 after tofacitinib initiation. In three patients information was obtained beyond 6 months, with 100% clinical, biochemical, and endoscopic remission and without requiring colectomy. In the case of the pediatric patient, symptom remission was achieved one week after starting tofacitinib, remaining in clinical, biochemical and endoscopic remission beyond 6 months. No serious adverse events were reported in any of the cases. ConclusionsTofacitinib represents a rescue therapeutic alternative in CUAG, with rapid clinical response, adequate tolerance and less need for colectomy, being sustained for periods beyond 6 months.

Risk of Venous Thromboembolism With Tofacitinib Versus Tumor Necrosis Factor Inhibitors in Cardiovascular Risk-Enriched Rheumatoid Arthritis Patients.

The ORAL Surveillance trial found a dose-dependent increase in venous thromboembolism (VTE) and pulmonary embolism (PE) events with tofacitinib versus tumor necrosis factor inhibitors (TNFi). We aimed to assess VTE incidence over time and explore risk factors of VTE, including disease activity, in ORAL Surveillance. Patients with rheumatoid arthritis (RA) aged 50 years or older with at least one additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily (BID) or TNFi. Post hoc, cumulative probabilities and incidence rates (patients with first events/100 patient-years) by 6-month intervals were estimated for adjudicated VTE, deep vein thrombosis, and PE. Cox regression models identified risk factors. Clinical Disease Activity Index leading up to the event was explored in patients with VTE. Cumulative probabilities for VTE and PE were higher with tofacitinib 10 mg BID, but not 5 mg BID, versus TNFi. Incidence rates were consistent across 6-month intervals within treatments. Across treatments, risk factors for VTE included prior VTE, body mass index greater than or equal to 35 kg/m2, older age, and history of chronic lung disease. At the time of the event, most patients with VTE had active disease as defined by Clinical Disease Activity Index. Incidences of VTE and PE were higher with tofacitinib (10 > 5 mg BID) versus TNFi and were generally consistent over time. Across treatments, VTE risk factors were aligned with previous studies in the general RA population. These data highlight the importance of assessing VTE risk factors, including age, body mass index, and VTE history, when considering initiation of tofacitinib or TNFi in patients with active RA.

DOP46 Tofacitinib for hospitalized acute severe Ulcerative Colitis – the TRIUMPH study

Abstract Background Tofacitinib is a rapidly acting Janus kinase (JAK) inhibitor with several case series reporting effectiveness in patients with acute severe ulcerative colitis (ASUC). However, there remains a paucity of prospective data evaluating its efficacy and rapidity of onset in ASUC. Methods The TRIUMPH study is a phase 4 prospective interventional trial of tofacitinib in ASUC conducted in five hospitals across Canada (Clinicaltrials.gov: NCT04925973). Patients with ASUC (biologic naïve and experienced) refractory to three days of intravenous corticosteroids (Modified Truelove-Witts Severity Index [MTWSI] &amp;gt; 10 despite steroids) were eligible for enrollment. Patients were treated with tofacitinib 10mg bid and assessed daily while in hospital. The primary outcome was day 7 clinical response (MTWSI reduction of &amp;gt; 3 from baseline and &amp;lt; 10). Secondary outcomes included rapidity of clinical and biomarker improvements over the first 7 days, colectomy over the course of one year, and corticosteroid-free clinical remission (total Mayo score &amp;lt; 2), endoscopic improvement (endoscopic Mayo score 0 or 1), and adverse events at 3, 6, and 12 months. Results This is an interim analysis as the study has been fully recruited with six-month follow-up available for all participants. 24 patients with ASUC were recruited and received tofacitinib 10mg bid. The mean total baseline Mayo score was 10.1 (SD 1.4) and all patients had a baseline Mayo endoscopic subscore of 2 (25%, 6/24) or 3 (75%, 18/24). One third of the patients (8/24) had previous anti-TNF failure. Day 7 clinical response was achieved in 58.3% (14/24) patients. The mean number of days to achieve clinical response was 2.4 days (SD 1.3). Marked reduction in C-reactive protein was observed in responders as soon as one day after tofacitinib initiation compared to non-responders (Figure 1). Colectomy occurred in 16.7% (4/24) patients by day 7 and 25% (6/24) by six months. At six months, 45.8% (11/24) patients remained on tofacitinib (including 78.6% (11/14) of day 7 responders), with 33.3% (8/24) having achieved endoscopic improvement and corticosteroid-free clinical remission. A total of six patients reported adverse events, one of which was considered severe (stroke at day 3 after initiation of tofacitinib). Conclusion Tofacitinib may be an effective induction strategy in patients hospitalized with steroid-refractory ASUC. Randomized controlled trials are needed to compare JAK inhibitors with infliximab for steroid refractory ASUC.

P943 Real world Effectiveness and safety of tofacitinib in patients with Ulcerative Colitis: 6 months follow-up of the French TOFAST study

Abstract Background TOFAST is an observational, prospective, multicenter cohort study aiming to describe the real-life clinical benefit of tofacitinib in moderate-to-severe Ulcerative Colitis (UC). Methods We report the results of the interim analysis after 6 months of follow-up, describing patient's characteristics, effectiveness, including change in daily PRO2 scores [RB and stool frequency (SF)] during the first 14 days and the median time to relief, and safety. Clinical response was defined as a decrease in partial Mayo score (PMS) (≥ 3 points and ≥30%) from inclusion with a concomitant decrease in rectal bleeding (RB) subscore ≥ 1 point (absolute subscore of 0 or 1). Clinical remission was defined as PMS ≤2 with no subscore &amp;gt;1. Symptomatic relief was reported by patients as the time in days from initiation of tofacitinib to improvement of their symptoms. Safety has been been reported as the % of Adverse Events (AE), serious AE and AE of special interest. Results 88 patients were included in the safety analysis (one patient was excluded from the effectiveness analysis as he did not meet the eligibility criteria) with a median exposure duration of 11.7 [Q1; Q3: 6.0; 22.1] months. Of these patients, 67 completed a 6-month follow-up visit by 15/07/2023 and were included in the effectiveness analysis. At inclusion 59.8% of patients were male with a mean (± SD) age of 37.5 ±13.2 years, a median disease duration of 5.9 years [Q1; Q3: 2.7; 13.1]. 46.5% of patients had pancolitis. The mean total Mayo Score was 8.1 ±2.4. 94.3% of patients had previously received at least one anti-TNF agent, 67.8% vedolizumab and 35.6% ustekinumab. Tofacitinib was initiated at 10 mg b.i.d, in combination with corticosteroids for 35.6% of patients. At 6 months, 53 (77.9%) patients were still treated with tofacitinib, 58.5% at 10 mg BID dose. Corticosteroids were ongoing in 22.9% of patients. Clinical response and remission were observed in 64.2% and 61.2% of patients, respectively. For the 68 (78.2%), patients who reported improvement the median time to relief was 7 days [Q1; Q3: 3.5 ;14.5]. PRO2 scores normalization during the first 14 days is shown in the figure. 84.1% of patients reported at least one adverse event (AE) and 21.6% reported at least one serious AE. Seventeen (19.3%) infections and 3 (3.4%) cases of herpes zoster were observed as well as one non-invasive low-grade urothelial carcinoma. No major cardiovascular or venous thromboembolic event, nor malignancy or death were observed (Table). Conclusion In this real-life cohort of patients with refractory UC, tofacitinib induced a clinical response and remission in over 60% of patients, with symptoms relief observed as early as the first two weeks. AEs were consistent with the known tofacitinib safety profile.

Tofacitinib: A Treatment Option for Recalcitrant Polymorphic Light Eruption and Its Mechanistic Rationale.

Background: Polymorphous light eruption is largely characterized by a delayed-type (type IV) hypersensitivity reaction to 1 or more undefined endogenous ultraviolet-induced skin antigens. Objectives: To evaluate the efficacy of tofacitinib in refractory cases of polymorphous light eruption. Methods: Seven patients who had failed multiple systemic treatments or relapsed within 2 weeks of existing systemic agents with concomitant photoprotection were offered tofacitinib after written consent. Results: Initiation of tofacitinib led to a marked reduction of itching (mean ± SD 3.1 ± 1.12 days) followed by clinical resolution (mean ± SD 2.6 ± 1.1 weeks). The duration of therapy ranged from 1 to 3 months (mean ± SD 2 ± 0.63 months), and 4 of 7 patients had a recurrence in 5.5 weeks and were again initiated on tofacitinib with a prompt response. Conclusion: Tofacitinib inhibits Janus kinase (JAK)1 and JAK3 thus it can abrogate the effects of the predominant cytokine milieu of polymorphic light eruption (PMLE) and thus reduce the expression of aberrant inflammatory T lymphocyte expression in PMLE.

Multicenter evaluation of tofacitinib retention and safety in rheumatoid arthritis - why cardiovascular risk factors do not equate to overt risk.

This multicenter, real-world, retrospective cohort study aimed to assess the effectiveness and safety of tofacitinib (TOFA) in rheumatoid arthritis (RA). Two hundred nine patients with active RA treated with TOFA, unresponsive to at least 2 conventional synthetic disease-modifying drugs, were recruited. Clinical characteristics were extracted from an electronic registry and supplemented with manual chart review and data linkage with ambulatory care. Drug retention and reasons for discontinuation were evaluated. Median (interquartile range) follow-up in the whole sample was 16.9 (5.93-31.7) months. Mean (standard deviation) age was 51.44 (±11.84) years, with female predominance (n = 168, 80.4%). Only 30 patients (14.4%) had no pre-existing traditional cardiovascular (CV) risk factor at TOFA initiation. Tofacitinib retention rates were high, with median survival estimated at 89.3% at 6 months, 82.4% at 12 months, and 60.4% at 24 months. Ineffectiveness was the primary cause of discontinuation (n = 50). The rate of adverse events (AEs) was relatively low, with lipid abnormalities, blood count alterations, and infectious events among the most common. No major adverse CV event was reported. The incidence rate of AEs necessitating treatment switch was 60.34 (95% CI: 37-92) per 1,000 person-years of follow-up. Presence of multiple (> 3) CV risk factors was associated with lower odds of TOFA retention and treatment effectiveness. Tofacitinib demonstrated high retention rates and a favorable safety profile in RA patients, including those with traditional CV risk factors. Tofacitinib may be a valuable treatment option for RA patients when combined with individualized CV risk management. Further studies are warranted to explore the long-term effects of TOFA and its CV impact in larger populations.

Experiencia colombiana con el uso de tofacitinib en colitis ulcerosa aguda grave: estudio de serie de casos

IntroductionTofacitinib is indicated in patients with moderate to severe ulcerative colitis (UC); however, given its rapid onset of action, it may constitute an alternative in patients with hospitalized severe acute UC. There are few data on this indication in the literature. The aim of this study was to describe the efficacy and safety of tofacitinib in the management of patients with hospitalized UC, as well as its clinical characteristics and other treatment patterns. Materials and methodsDescriptive observational study of adults and children with CUAG treated with tofacitinib between June 2019 and December 2022 in Colombia. Sociodemographic and clinical variables were collected, therapeutic response was evaluated in different periods of time and descriptive analysis of quantitative and qualitative variables was performed. ResultsSix patients (five adults and one pediatric), mean age 33.2 (SD: 8.5) years, with CUAG. Symptom remission was obtained in 100% of patients at day 7 after tofacitinib initiation. In three patients information was obtained beyond 6 months, with 100% clinical, biochemical, and endoscopic remission and without requiring colectomy. In the case of the pediatric patient, symptom remission was achieved one week after starting tofacitinib, remaining in clinical, biochemical and endoscopic remission beyond 6 months. No serious adverse events were reported in any of the cases. ConclusionsTofacitinib represents a rescue therapeutic alternative in CUAG, with rapid clinical response, adequate tolerance and less need for colectomy, being sustained for periods beyond 6 months.

Tofacitinib therapy in refractory inflammatory myositis: a retrospective cohort study of 41 patients.

To evaluate the efficacy and safety of tofacitinib in treatment-refractory inflammatory myositis in a real-world clinical setting. All patients with refractory inflammatory myositis treated with tofacitinib from a single urban centre in Vancouver, British Columbia, Canada, were included from June 2016 to December 2022. The medical records of these patients were retrospectively reviewed. A total of 41 patients were included, 23 with classic DM, 12 with amyopathic DM (ADM) and six with PM phenotype. The patients failed an average of four to five non-steroidal immunosuppressants before initiation of tofacitinib. In the classic DM and ADM group, tofacitinib offered clinically and statistically significant cutaneous improvement. In all myositis patients including the PM phenotype, no meaningful muscle strength response to tofacitinib was observed. 53.7% of the patients discontinued tofacitinib due to lack of benefit or death. Of the 19 patients who remained on tofacitinib at the conclusion of this study, tofacitinib demonstrated clinically and statistically significant improvement in cutaneous disease activity. Tofacitinib appears to be highly effective in targeting cutaneous manifestations in classic DM and ADM; however, minimal benefit in muscle strength in the DM or PM phenotype were observed.

Real-world Evidence Comparing Tofacitinib and Vedolizumab in Anti-TNF-experienced Patients With Ulcerative Colitis.

Antitumor necrosis factor (anti-TNF) inhibitors are first-line treatment among patients with ulcerative colitis (UC). With time, patients tend to lose response or become intolerant, necessitating switching to small cell biologics such as tofacitinib or vedolizumab. In this real-world study of a large, geographically diverse US population of TNF-experienced patients with UC, we evaluated the effectiveness and safety of newly initiating treatment with tofacitinib vs vedolizumab. We conducted a cohort study using secondary data from a large US insurer (Anthem, Inc.). Our cohort included patients with UC newly initiating treatment with tofacitinib or vedolizumab. Patients were required to have evidence of treatment with anti-TNF inhibitors in the 6 months prior to cohort entry. The primary outcome was treatment persistence >52 weeks. Additionally, we evaluated the following secondary outcomes as additional measures of effectiveness and safety: (1) all-cause hospitalization; (2) total abdominal colectomy; (3) hospitalization for infection; (4) hospitalization for malignancy; (5) hospitalization for cardiac events; and (6) hospitalization for thromboembolic events. We used fine stratification by propensity scores to control for confounding by demographics, clinical factors, and treatment history at baseline. Our primary cohort included 168 new users of tofacitinib and 568 new users of vedolizumab. Tofacitinib was associated with lower treatment persistence (adjusted risked ratio, 0.77; 95% CI, 0.60 -0.99). Differences in secondary measures of effectiveness or safety between tofacitinib initiators vs vedolizumab initiators were not statistically significant (all-cause hospitalization, adjusted hazard ratio, 1.23; 95% CI, 0.83-1.84; total abdominal colectomy, adjusted HR, 1.79; 95% CI, 0.93-3.44;and hospitalization for any infection, adjusted HR, 1.94; 95% CI, 0.83-4.52). Ulcerative colitis patients with prior anti-TNF experience initiating tofacitinib demonstrated lower treatment persistence compared with those initiating vedolizumab. This finding is in contrast to other recent studies suggesting superior effectiveness of tofacitinib. Ultimately, head-to-head randomized, controlled trials that focus on directly measured end points may be needed to best inform clinical practice.

Comparing Patient Reported Outcomes among Anti-TNF Experienced Patients with Ulcerative Colitis Initiating Vedolizumab versus Tofacitinib

Abstract Background Primary and secondary non-response to Anti-Tumor Necrosis Factor (TNF) therapy is common in patients with ulcerative colitis (UC), yet limited research has compared the effectiveness of subsequent biological therapy. Objective We sought to compare the effectiveness of vedolizumab and tofacitinib in anti-TNF experienced patients with UC, focusing on patient-prioritized patient reported outcomes (PROs). Methods We conducted a prospective cohort study nested within the Crohn’s &amp; Colitis Foundation’s IBD Partners and SPARC IBD initiatives. We identified anti-TNF experienced patients with UC initiating vedolizumab or ustekinumab and analyzed PROs reported approximately 6 months later (minimum 4 months, maximum 10 months). Co-primary outcomes were Patient Reported Outcome Measurement Information System (PROMIS) domains of Fatigue and Pain Interference. Secondary outcomes included PRO-2, treatment persistence, and need for colectomy. Results We compared 72 vedolizumab initiators and 33 tofacitinib initiators. At follow-up, Pain Interference (P=0.04), but not Fatigue (P=0.53,) was lower among tofacitinib initiators. A trend towards higher Social Role Satisfaction was not significant. The remainder of secondary outcomes (PRO2, treatment persistence, colectomy) did not differ between treatment groups. Conclusion Among anti-TNF experienced patients with UC, Pain Interference 4-10 months after treatment initiation was lower among tofacitinib users as compared to vedolizumab users. Many, but not all, secondary endpoints and subanalyses also favored favored tofacitinib. Future studies with larger sample sizes are needed to further evaluate these findings.

P450 Real life Effectiveness and safety of an induction treatment with tofacitinib in patients with Ulcerative Colitis: First results of the French TOFAST cohort

Abstract Background We report the results of TOFAST, a French ongoing prospective observational multicenter study, evaluating the clinical benefit of tofacitinib for the treatment of moderate to severe UC. Methods In this descriptive interim analysis, effectiveness and safety were assessed at the end of induction therapy (up to 4 months after tofacitinib initiation). Clinical response was defined as a decrease in partial Mayo score (PMS) (≥ 3 points and ≥ 30%) from inclusion with a concomitant decrease in rectal bleeding (RB) subscore ≥ 1 point (absolute subscore of 0 or 1). Clinical remission was defined as PMS ≤2 with no subscore &amp;gt;1. Change in daily PRO2 scores [RB and stool frequency (SF)] during the first 14 days and the median time to patient relief were also analyzed. Results Among the 102 patients included, 86 had available data at the first follow-up visit, corresponding to the end of induction period. At inclusion, 53.9% of patients were male with a mean (± SD) age of 37.1 ±13.6 years, a median disease duration of 6.1 years [Q1; Q3: 2.8; 10.8]. 48% of patients had pancolitis and 24.5% an extraintestinal manifestation; mean PMS was 6 ±1.8 with median SF and RB scores of 3.0 [Q1; Q3: 2.0; 3.0] and 2.0 [1.0; 2.0], respectively. Regarding prior drug exposure, 92.2% of patients had received at least one anti-TNF agent, 62.7% vedolizumab and 34.3% ustekinumab. Tofacitinib was initiated at 10 mg b.i.d, in combination with 5-ASA and corticosteroids for 19.6% and 33.3% of patients, respectively. At the first follow-up visit (median 1.9 months after treatment initiation), tofacitinib was ongoing in 87.2%, mostly (73.3%) at 10 mg b.i.d. Corticosteroids were ongoing in 29.1% of patients. At the end of induction period, rates of clinical response and remission were 52.3% and 43%, respectively. Median changes in RB and SF scores were identical at days 7 and 14, -1 point [Q1; Q3: -1.0; 0.0] and -1 point [Q1; Q3: -2.0 - 0.0], respectively. For patients who reported improvement (68.6%), the median time to relief was 7 days [Q1-Q3: 4.0-15.0]. PRO2 scores normalisation during the first 14 days is shown in the figure. RRegarding safety, 73.5% of patients reported at least one adverse event (AE) and 12.6% reported at least one serious AE. Ten (9.8%) infections (none considered as serious) and 2 (1.9%) Herpes Zoster were reported. No major cardiovascular or venous thromboembolic event, nor malignancy or death were observed (Table). Conclusion The interim results of TOFAST study show that at the end of induction therapy with tofacitinib, 52.3% of patients achieved clinical response and &amp;gt;40% achieved remission. Rapid improvement in SF and RB scores was observed within 2 weeks. AEs were consistent with the known tofacitinib safety profile.

Characteristics, clinical outcomes and patient-reported outcomes of patients with ulcerative colitis receiving tofacitinib: a real-world survey in the United States and five European countries

BackgroundTo describe variations in treatment patterns, clinical outcomes, patient-reported outcomes (PRO), and physician and patient satisfaction in patients with moderate-to-severe ulcerative colitis (UC) treated with tofacitinib in a real-world setting.MethodsData were drawn from the Adelphi UC Disease Specific Programme™, a point-in-time survey of physicians and their consulting patients in the US and Europe. For inclusion in this analysis, gastroenterologists completed medical record forms for the next seven consecutive consulting patients with confirmed UC, plus a further two patient record forms for patients treated with tofacitinib. Those same patients then completed a patient-reported questionnaire.ResultsGastroenterologists (n = 340) provided data for 2049 patients with UC, including 642 patients receiving tofacitinib. Physicians’ most frequent reason for choosing tofacitinib was overall efficacy (71.3% of patients). The proportion of patients in remission increased with length of treatment, from 13.7% at [0, 4) weeks to 68.3% at [52+] weeks. Both physicians and patients reported that the Mayo components of stool frequency and blood in stool were reduced with time on treatment. Improvement in symptoms (bloody diarrhea, abdominal pain/cramps, urgency, rectal bleeding, fatigue/tiredness) was reported in the first weeks of treatment, and increased with time. At week [52+], mean score reductions from treatment initiation to current in overall symptom severity, pain, and fatigue were 2.2 (to a current mean score of 1.1), 2.2 (to 0.9), and 2.1 (to 1.0), respectively. Comparing patients at weeks [0, 4) and [52+] (all PROs, p < 0.0001), the increase in EQ-5D-5L index total score was 0.29 points and in SIBDQ total score was 20.5 points; percent reductions in WPAI absenteeism was 34.4%, presenteeism 26.8%, overall work impairment 40.9% and activity impairment was 28.3%. These changes reached the thresholds for minimally clinically important differences. The majority of physicians (91.9%) and patients (93.5%) were satisfied with tofacitinib at week [52+].ConclusionPatients with moderate-to-severe UC treated with tofacitinib show considerable improvement in symptoms and quality of life from tofacitinib initiation to one year and beyond, with high rates of remission. Physicians and patients report satisfaction with UC control at recommended doses in a mostly biologic experienced population.

Efficacy and Safety of Tofacitinib in Rheumatoid Arthritis (RA): A Retrospective Study From Two Centers in Jeddah, Saudi Arabia.

Tofacitinib is the first Janus kinase (JAK) inhibitor approved for treating rheumatoid arthritis (RA). Several clinical trials have evaluated the safety and effectiveness of tofacitinib in adult patients with moderately to severely active RA. Real-world studies provide invaluable insights into routine clinical practice. We aim to assess the clinical efficacy and safety of RA patients. Over a period of two years, we included 50 consecutive RA patients who were treated with tofacitinib. Clinical disease activity, assessed by disease activity score (DAS) 28 - erythrocyte sedimentation rate (ESR), as well as adverse events (AEs) were evaluated. A total of 50 patients (84% female) were enrolled in the study. The mean age at initiation of tofacitinib was 48.54 ± 15.97 years. The mean time of treatment with tofacitinib was 18.06 ± 2.04 months. Patients were treated with tofacitinib 5 mg BID with 32% receiving tofacitinib as monotherapy. A total of 74% of the patients had been prescribed at least one biological treatment. The treatment target was achieved in 42 patients (82%). Baseline characteristics and previous treatment regimens did not predict clinical response to tofacitinib. Fifteen patients discontinued the treatment: seven due to ineffectiveness, four due to pregnancy, and five due to adverse events. The most common infectious adverse event was herpes zoster (4%) while the most common observed laboratory abnormalities were elevation in low density lipoprotein (LDL) and high density lipoprotein (HDL) in 6% and 8% of the patients, respectively. Our results indicate that tofacitinib is effectivein real-world settingseven as monotherapy. The treatment target was attained by 82% of the patients on tofacitinib. The safety profile of tofacitinib was generally consistent with previous studies.

Timing of tofacitinib therapy is critical to improving outcomes in severe-critical COVID-19 infection: A retrospective study from a tertiary care hospital.

Describe the use of tofacitinib in severe and critical coronavirus disease-2019 (COVID-19), and explore the association of drug initiation time with survival. A retrospective study of inpatients with severe or critical COVID-19 at a tertiary care hospital, who were prescribed generic tofacitinib for at least 48 hours, was conducted. Baseline demographics, comorbidities, illness severity, treatment, adverse effects and outcomes were analyzed. Patients were grouped based on median duration of symptomatic illness prior to tofacitinib administration, as early or late initiation groups. Forty-one patients ([85.4% males], mean age 52.9 ± 12.5 years), were studied. 65.9% (n = 27) had severe COVID-19, while 34.1% (n = 14) were critically ill. Death occurred in 36.6% patients (n = 15). The median time to prescription of tofacitinib was 13 (9.50, 16.0) days of symptom onset. Tofacitinib was initiated early (8-13 days) in 56.1% of patients (n = 23), while the remaining received it beyond day 14 of symptom onset (late initiation group). Multivariate logistic regression adjusted for age, presence of diabetes mellitus and illness duration prior to hospitalization demonstrated higher odds of survival (adjusted odds ratio 19.3, 95% confidence interval 2.57, 145.2) in the early initiation group, compared to the late initiation group. Early initiation of tofacitinib in severe and critical COVID-19 has potential to improve survival odds.

S1043 Tofacitinib for the Treatment of Pouch-Related Disorders: A Case Series

S1043 Tofacitinib for the Treatment of Pouch-Related Disorders: A Case Series

S2767 Rapid Recurrence of Stroke After Tofacitinib Initiation: Composite Outcomes Challenge Informed Decision-Making in Ulcerative Colitis Management

S2767 Rapid Recurrence of Stroke After Tofacitinib Initiation: Composite Outcomes Challenge Informed Decision-Making in Ulcerative Colitis Management