***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Patients with rheumatoid arthritis ( RA ) have an increased cardiovascular ( CV ) risk . This study aim ed to analyze the effects of Tofacitinib treatment , a Janus kinase inhibitor , on atherosclerosis in patients with RA . Patients with an active RA ( 28-joint disease activity score – erythrocyte sedimentation rate > 3.2 ) despite methotrexate ( MTX ) treatment 12 mg/week were included in this open-label prospect i ve study and started on Tofacitinib ( 10 mg/day , 5 mg twice/day ) . Japanese guideline does not allow high dose of MTX . All patients used a stable dosage of MTX , steroids , and statins or lipid-lowering drugs . The primary endpoint was the comparison of the carotid intima-media thickness ( CIMT ) at the baseline and 54 weeks after Tofa treatment . Clinical data were collected at regular visits . Forty-six patients completed this study . CIMT did not significantly change from baseline to 54 weeks ( 1.09 ± 0.69 and 1.08 ± 0.78 mm , p = 0.82 ) . In 12 patients who had atherosclerosis at baseline ( carotid intima-media thickness > 1.10 mm ) , there was a significant decrease in CIMT ( 0.05± 0.026 mm ; p < 0.05 ) . However , the decrease in CIMT was of limited clinical significance . Tofacitinib increased fasting total cholesterol levels from baseline to 54 weeks ( 216 ± 25.3 and 234 ± 28.8 mg/dL , p < 0.01 ) . Tofacitinib affects atherosclerosis in patients with active RA  The CIMT in RA patients was stable . Tofacitinib decreased the CIMT of patients who had increased CIMT at baseline . Tofacitinib reduced RA disease activity and limited vascular damage despite up-regulating cholesterol in patients with an active RA BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon for which current treatments are not universally effective . One additional treatment may be tofacitinib ( CP-690,550 ) , an oral inhibitor of Janus kinases 1 , 2 , and 3 with in vitro functional specificity for kinases 1 and 3 over kinase 2 , which is expected to block signaling involving gamma chain-containing cytokines including interleukins 2 , 4 , 7 , 9 , 15 , and 21 . These cytokines are integral to lymphocyte activation , function , and proliferation . METHODS In a double-blind , placebo-controlled , phase 2 trial , we evaluated the efficacy of tofacitinib in 194 adults with moderately to severely active ulcerative colitis . Patients were r and omly assigned to receive tofacitinib at a dose of 0.5 mg , 3 mg , 10 mg , or 15 mg or placebo twice daily for 8 weeks . The primary outcome was a clinical response at 8 weeks , defined as an absolute decrease from baseline in the score on the Mayo scoring system for assessment of ulcerative colitis activity ( possible score , 0 to 12 , with higher scores indicating more severe disease ) of 3 or more and a relative decrease from baseline of 30 % or more with an accompanying decrease in the rectal bleeding subscore of 1 point or more or an absolute rectal bleeding subscore of 0 or 1 . RESULTS The primary outcome , clinical response at 8 weeks , occurred in 32 % , 48 % , 61 % , and 78 % of patients receiving tofacitinib at a dose of 0.5 mg ( P=0.39 ) , 3 mg ( P=0.55 ) , 10 mg ( P=0.10 ) , and 15 mg ( P<0.001 ) , respectively , as compared with 42 % of patients receiving placebo . Clinical remission ( defined as a Mayo score ≤2 , with no subscore > 1 ) at 8 weeks occurred in 13 % , 33 % , 48 % , and 41 % of patients receiving tofacitinib at a dose of 0.5 mg ( P=0.76 ) , 3 mg ( P=0.01 ) , 10 mg ( P<0.001 ) , and 15 mg ( P<0.001 ) , respectively , as compared with 10 % of patients receiving placebo . There was a dose-dependent increase in both low-density and high-density lipoprotein cholesterol . Three patients treated with tofacitinib had an absolute neutrophil count of less than 1500 . CONCLUSIONS Patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00787202 . ) OBJECTIVE The purpose of this 24-month phase III study was to examine structural preservation with tofacitinib in patients with rheumatoid arthritis ( RA ) with an inadequate response to methotrexate ( MTX ) .  Data from a planned 12-month interim analysis are reported . METHODS In this double-blind , parallel-group , placebo-controlled study , patients receiving background MTX  were r and omized 4:4:1:1 to tofacitinib at 5 mg twice daily , tofacitinib at 10 mg twice daily , placebo to tofacitinib at 5 mg twice daily , and placebo to tofacitinib at 10 mg twice daily . At month 3 , nonresponder placebo-treated patients were advanced in a blinded manner to receive tofacitinib as indicated above ; remaining placebo-treated patients were advanced at 6 months . Four primary efficacy end points were all analyzed in a step-down procedure . RESULTS At month 6 , response rates according to the American College of Rheumatology 20 % improvement criteria for tofacitinib at 5 mg and 10 mg twice daily were higher than those for placebo ( 51.5 % and 61.8 % , respectively , versus 25.3 % ; both P < 0.0001 ) . At month 6 , least squares mean ( LSM ) changes in total modified Sharp/van der Heijde score for tofacitinib at 5 mg and 10 mg twice daily were 0.12 and 0.06 , respectively , versus 0.47 for placebo ( P = 0.0792 and P ≤ 0.05 , respectively ) . At month 3 , LSM changes in the Health Assessment Question naire disability index score for tofacitinib at 5 mg and 10 mg twice daily were -0.40 ( significance not declared due to step-down procedure ) and -0.54 ( P < 0.0001 ) , respectively , versus -0.15 for placebo . At month 6 , rates of remission ( defined as a value < 2.6 for the 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate ) for tofacitinib at 5 mg and 10 mg twice daily were 7.2 % ( significance not declared due to step-down procedure ) and 16.0 % ( P < 0.0001 ) , respectively , versus 1.6 % for placebo . The safety profile was consistent with findings in previous studies . CONCLUSION Data from this 12-month interim analysis demonstrate that tofacitinib inhibits progression of structural damage and improves disease activity in patients with RA who are receiving MTX OBJECTIVE To determine the efficacy , safety , and tolerability of 3 different dosages of CP-690,550 , a potent , orally active JAK inhibitor , in patients with active rheumatoid arthritis ( RA ) in whom methotrexate , etanercept , infliximab , or adalimumab caused an inadequate or toxic response . METHODS Patients ( n = 264 ) were r and omized equally to receive placebo , 5 mg of CP-690,550 , 15 mg of CP-690,550 , or 30 mg of CP-690,550 twice daily for 6 weeks , and were followed up for an additional 6 weeks after treatment . The primary efficacy end point was the American College of Rheumatology 20 % improvement criteria ( ACR20 ) response rate at 6 weeks . RESULTS By week 6 , the ACR20 response rates were 70.5 % , 81.2 % , and 76.8 % in the 5 mg , 15 mg , and 30 mg twice daily groups , respectively , compared with 29.2 % in the placebo group ( P < 0.001 ) . Improvements in disease activity in CP-690,550-treated patients compared with placebo were seen in all treatment groups as early as week 1 . ACR50 and ACR70 response rates significantly improved in all treatment groups by week 4 . The most common adverse events reported were headache and nausea . The infection rate in both the 15 mg twice daily group and the 30 mg twice daily group was 30.4 % ( versus 26.2 % in the placebo group ) . No opportunistic infections or deaths occurred . Increases in mean low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels , and increases in mean serum creatinine level ( 0.04 - 0.06 mg/dl ) were seen in all CP-690,550 treatment arms . CONCLUSION Our findings indicate that CP-690,550 is efficacious in the treatment of RA , result ing in rapid , statistically significant , and clinical ly meaningful reductions in the signs and symptoms of RA . Further studies of CP-690,550 in RA are warranted Background Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis . We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor ( TNF ) inhibitors . Methods In this 6‐month r and omized , placebo‐controlled , double‐blind , phase 3 trial , we r and omly assigned 395 patients , in a 2:2:1:1 ratio , to four regimens : 5 mg of tofacitinib administered orally twice daily ( 132 patients ) ; 10 mg of tofacitinib twice daily ( 132 patients ) ; placebo , with a switch to 5 mg of tofacitinib twice daily at 3 months ( 66 patients ) ; or placebo , with a switch to 10 mg of tofacitinib twice daily at 3 months ( 65 patients ) . Data from the patients who received placebo during the first 3 months of the trial were pooled . The primary end points were the percentage of patients who had at least 20 % improvement according to the criteria of the American College of Rheumatology ( ACR20 response ) and the change from baseline score on the Health Assessment Question naire – Disability Index ( HAQ‐DI ; scores range from 0 to 3 , with higher scores indicating greater disability ) at the month 3 analysis . Results At 3 months , the rates of ACR20 response were 50 % with the 5‐mg dose of tofacitinib and 47 % with the 10‐mg dose , as compared with 24 % with placebo ( P<0.001 for both comparisons ) ; the corresponding mean changes from baseline in HAQ‐DI score were ‐0.39 and ‐0.35 , as compared with ‐0.14 ( P<0.001 for both comparisons ) . Serious adverse events occurred in 4 % of the patients who received the 5‐mg dose of tofacitinib continuously and in 6 % who received the 10‐mg dose continuously . Over the course of 6 months , there were four serious infections , three herpes zoster infections , one myocardial infa rct ion , and one ischemic stroke among the patients who received tofacitinib continuously . Elevations of aspartate and alanine aminotransferase concentrations of three or more times the upper limit of the normal range occurred in more patients who received tofacitinib continuously than in patients who received placebo followed by tofacitinib . Conclusions In this trial involving patients with active psoriatic arthritis who had had an inadequate response to TNF inhibitors , tofacitinib was more effective than placebo over 3 months in reducing disease activity . Adverse events were more frequent with tofacitinib than with placebo . ( Funded by Pfizer ; OPAL Beyond Clinical Trials.gov number , NCT01882439 . Objectives To compare efficacy and safety of various doses of tofacitinib , an oral Janus kinase inhibitor , with placebo in patients with active ankylosing spondylitis ( AS , radiographic axial spondyloarthritis ) . Methods In this 16-week ( 12-week treatment , 4-week washout ) , phase II , multicentre , dose-ranging trial , adult patients with active AS were r and omised ( N=51 , 52 , 52 , 52 , respectively ) to placebo or tofacitinib 2 , 5 or 10 mg twice daily . The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 2 
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Conclusion : Compared with placebo , there was no augmented risk of CVEs and all-cause mortality in patients with IMIDs following tofacitinib treatment in a short-term perspective , whereas 10 mg twice daily tofacitinib appeared to be associated with reduction in cardiovascular and all-cause mortality risks , except VTEs , relative to the 5 mg twice daily dose .