year in review - best papers in ra & spa - dr banwari sharma

YEAR IN REVIEW: RA &SPA

BANWARI SHARMA CLINICAL IMMUNOLOGIST & RHEUMATOLOGIST,

JAIPUR.

Outline

• Top papers of Rheumatoid Arthritis 2015-16• Few landmark studies with brief discussion• Top papers of AS & PsA 2015-16• Few landmark studies with brief discussion

Magnetic Resonance Imaging–Detected Features of Inflammation and Erosions in Symptom-Free Persons From the General Population

L. Mangnus, H. W. van Steenbergen, M. Reijnierse, A. H. M. van der Helm-van Mil. Arthritis Rheumatol. 2016 Nov;68(11):2593-2602. doi: 10.1002/art.39749. Epub 2016 Sep 29.

• Electronic medical record database ( THIN) UK general population• RA versus without RA ( 1:5)• Matched for age, sex & year of diagnosis

between1999 & 2014. • Early cohort (1999–2006) /Late cohort (2007–

2014).• Mortality rates: RA versus non-RA cohorts

Improved Survival Of RA Patients

• Widespread use of MTX ( 68% V/S 85%)• csDMARD use( 65% V/S 81%)• Use of TNFi and other biologicals • T-2-T• Combination of all the above measures

10 YEARS OUTCOME DATA

SequentialMonotherapy ( n=126)

Step-up Combination ( n=121)

Initial Combination Therapy with Prednisolone ( n=133)

Initial Combination therapy with Infliximab ( n=128)

Total

Low disease activity (%)

84.7 73.8 85.7 84.3 82

Remission (%)

50.0 45.9 57.1 56.2 53

Drug free remission (%)

8.7 9.1 9.0 10.2 14

Dropout/Missing (%)

41.3 44.6 42.1 28 38

10 YEARS OUTCOME DATA

HAQ Mean 0.57

Radiographic Damage ( Sharp-van der Heijde Score Mean)

11,8,8,and 6

Standardized Mortality Ratio 1.16

CONCLUSION: T-2-T strategies in early RA 10 years result

• Rapid response in initial combination therapy with CS/Infliximab

• Similar efficacy and toxicity at 10 years• Functional outcome excellent• Minimal radiographic damage• Survival similar to general population

U-Act-Early

• DMARD naïve RA pts• Mean disease duration 26 days • N=317 ,108 MTX, 103 TCZ, 106 MTX+ TCZ• MTX (10 mg- 30 mg/wk), MTX+ Tocilizumab,

Tocilizumab (8mg/kg IVI monthly) alone • Primary endpoint: sustained remission ( DAS 28 <2.6 for ≥ 24 weeks)

MTX MTX+ TCZ TCZ

Dropout rate 28 26 22

Sustained remission n (%) on initial regimen (DAS28 < 2.6 ≥ 24 wks)

44 86 83

Sustained remission n (%) for entire study : 2 years

77 86 88

Sustained drug free remission, n ( %)

11 35 27

MTX MTX+ TCZ TCZ

HAQ, at week 104 mean (SD) n

0.62 (0.50), 73 0.48 (0.55), 70 0.61 (0.61), 77

Radiographic progression( Sharp-van der Hejde Score week 104) change from baseline mean (SD)/median

1.53 (2.421)/0.00(0.00–2.56)

1.18 (3.919)/0.00(0.00–1.00)

1.45 (4.272)/0.00(0.00–2.00)

CONCLUSION: T-2-T strategy in early DMARD naïve

• TCZ± Methotrexate : More effective with similar safety profile as compared to MTX monotherapy• Efficacy of TCZ alone similar to TCZ+MTX• Sustained drug free remission rate : 35%

SPONDYLOARTHROPATHY ( SpA)

• What is the progression rate of nr-axSpA to r-axSpA ?• What are the predisposing factors for this ?

• Recent onset SpA( Mean symptom duration:18 months)

• N=449 baseline & 2 years pelvic radiographs • MRI SIJ +: 37%• HLA-B27 +: 61%

RESULTS

• The potential baseline predisposing factors for developing mNY criteria:

• Current smokers: odds-ratio: 3.3, 95% ci 1.0 - 11.5

• HLAB27 positivity : odds-ratio: 12.6, 95% CI 2.3 - 274

• MRI-SIJ positivity: odds-ratio: 48.8, 95% CI 9.3 - 904

CONCLUSION

• Structural progression exist but is quite small & observed in a small number of patients:

• Smoking• HLAB27 positivity• MRI-SIJ positivity Independent predisposing factors of progression

TICOPA Study

• Open-label multicentre randomized controlled trial• N=206, < 2 Years, DMARD Naïve • Tight Control Group ( N=101): Monthly assessment &

treatment adjustment with aim to achieve MDA• Standard Care ( N=105): assessment every 3 months • Primary outcome: proportion of patients achieving

ACR20 response at 48 weeks

• Dactylitis, Enthesitis: No improvement • Radiographic Damage: No difference in both

the strategies • Cost: More ( approximately double) in tight

control • Adverse Reactions: More serious adverse

events in tight control group ( 25 V/S 8)

CONCLUSION

• Results of this study suggest tight control by T-2-T improves outcomes in newly diagnosed PsA

MEASURE 1 MEASURE 2

Number of patients (n) 371 219

Study protocol 10mg/kg IV Secukinumab or matched placebo at week 0,2, 4 followed by SC Secukinumab 150 mg or 75 mg every 4 weeks starting from 8th week

150 or 75 mg SC Secukinumab at week 1, 2, and 3 and every 4 weeks starting at week 4

Primary end point Proportion of pts with ASAS 20 response at week 16

Proportion of pts with ASAS 20 response at week 16

ADVERSE REACTIONS

• Four cancers were reported in MEASURE 1: 3 Secukinumab group ( B-cell lymphoma, breast

Ca, Transitional cell Ca of the bladder and lymphoma (placebo).

• Crohn’s disease:3 MEASURE 1, 2 MEASURE 2

CONCLUSION

• 150 mg SC Secukinumab with SC or IV loading effective in AS at week 16.• 75 mg Secukinumab effective with higher IV

loading dose.

Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis(FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial.

McInnes IB1, Mease PJ2, Kirkham B3, Kavanaugh A4, Ritchlin CT5, Rahman P6, van der Heijde D7, Landewé R8, Conaghan PG9, Gottlieb AB10, Richards H11, Pricop L12, Ligozio G12, Patekar M13, Mpofu S11; FUTURE 2 Study Group. Lancet. 2015 Sep 19;386(9999):1137-46.

FUTURE 2

• N=397• Double blind, placebo controlled, multicenter randomized trial• 65% pts anti-TNF naïve• 47% concomitant MTX• 300 mg, 150 mg, 75 mg & Placebo SC once in

a wk for 4 weeks then every 4 wks• Primary end point: ACR 20 response at wk 24

ADVERSE EFFECTS

• 94% pts completed 24 weeks & 84% completed week 52 period therapy

• URTI, Nasopharyngitis most common in all Secukinumab groups

• Candida infection 11: Oral, Vulvovaginal, Esophageal

• TB: zero• Squamous cell Carcinoma: 3, MI:1

CONCLUSION

• ACR 20 at WK 24: Better with all Secukinumab doses than placebo.

• Other efficacy outcomes: improvement with 300 & 150 mg but improvement with 75 mg not significant.

• Psoriasis symptoms improved better with 300 mg dose than 150 mg

• Efficacy in both anti-TNF naïve and IR pts

SUMMARY

• T-2-T, improves drug free remission/ remission & long term radiographic damage.

• Rate of progression in recent onset SpA is small. Smoking, HLA-B27+ & SI Joint inflammation on MR are independent predisposing factors.

• T-2-T improves outcome in early PsA.• Secukinumab is effective in both AS and PsA.

THANK YOU