Saturday, 4 January 2014

10 out of 10 - My favourite 10 rheumatology papers from 2013

10 out of 10 in 2013 – My favourite 10 Rheumatology Articles in 2013

With Christmas and New Year celebrations now over, you’ve had your dose of the Top 10 songs for the year end. Here are my favourite 10 papers from 2013. I have chosen original papers and have not included reviews, recommendations or meta-analyses. I have also focused on clinical papers as I could make another list of basic science papers. There are many other papers which are worthy of mention but to keep to 10, here is my list. I provide a short synopsis of each paper. For further details, please refer to the original references.

10. The effect of vitamin D supplementation on inflammatory and hemostatic markers and disease activity in patients with systemic lupus erythematosus: a randomized  placebo-controlled trial.

Abou-Raya A, Abou-Raya S, Helmii M. J Rheumatol. 2013 Mar;40(3):265-72. Epub 2012 Dec 1.

This paper assesses vitamin D status in patients with SLE and determined alterations in inflammatory and haemostatic markers and disease activity before and after vitamin D supplementation. This is done on the basis that Vitamin D has immunomodulatory functions.

Patients with SLE received either oral cholecalciferol 2000 IU/day or placebo for 12 months.  Serum levels between 10 and 30 ng/ml were classified as vitamin D insufficiency and levels < 10 ng/ml as vitamin D deficiency. The mean 25(OH)D level at baseline was 19.8 ng/ml in patients compared to 28.7 ng/ml in controls. The overall prevalence of suboptimal and deficient  25(OH)D serum levels among patients with SLE at baseline was 69% and 39%, respectively. Lower 25(OH)D levels correlated significantly with higher SLE disease activity. At 12 months of therapy, there was a significant improvement in levels of inflammatory and haemostatic markers as well as disease activity in the treatment group compared to the placebo group.

Vitamin D supplementation in patients with SLE improves infflammatory and haemostatic markers and show a tendency toward subsequent clinical improvement

9. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial.

Schiff M, Weinblatt ME, Valente R, van der Heijde D, Citera G, Elegbe A,
Maldonado M, Fleischmann R. Ann Rheum Dis. 2014 Jan 1;73(1):86-94. Epub
2013 Aug 20.

The second head to head study of biologics in RA in 2013. This study compares over 2 years the safety, efficacy and radiographic outcomes of subcutaneous abatacept (125 mg weekly) versus adalimumab (40mg every 2 weeks), in combination with stable dose of methotrexate (MTX).

The ACR 20, 50 and 70 responses at year 2 were 59.7%, 44.7% and 31.1% for abatacept and 60.1%, 46.6% and 29.3% for adalimumab. There were similar rates of adverse events (AEs) and serious adverse events (SAEs) but there were less discontinuations due to AEs, SAEs, serious infections and fewer local ISRs with abatacept. In RA patients with an inadequate response to MTX, subcutaneous abatacept and adalimumab were similarly efficacious based on clinical, functional and radiographic outcomes. Overall, AE frequency was similar in both groups

8. Surgery versus physical therapy for a meniscal tear and osteoarthritis.

Katz JN, Brophy RH, Chaisson CE, de Chaves L, Cole BJ, Dahm DL, Donnell-Fink LA, Guermazi A, Haas AK, Jones MH, Levy BA, Mandl LA, Martin SD, Marx RG, Miniaci A, Matava MJ, Palmisano J, Reinke EK, Richardson BE, Rome BN, Safran-Norton CE, Skoniecki DJ, Solomon DH, Smith MV, Spindler KP, Stuart MJ, Wright J, Wright RW, Losina E. N Engl J Med. 2013 May 2;368(18):1675-84. Epub 2013 Mar 18.

This paper helps answer the question whether arthroscopic partial meniscectomy for symptomatic patients with a meniscal tear and knee osteoarthritis results in better functional outcomes than nonoperative therapy. Symptomatic patients 45 years of age or older with a meniscal tear and evidence of mild-to-moderate osteoarthritis on imaging were randomly assigned to surgery and postoperative physical therapy or to a standardized physical-therapy regimen 

The mean improvement in the WOMAC score after 6 months was 20.9 points in the surgical group and 18.5 in the physical-therapy group (mean difference, 2.4 points). At 6 months, 51 active participants in the study who were assigned to physical therapy alone (30%) had undergone surgery. The frequency of adverse events did not differ significantly between the groups. There was no significant difference between the study groups in functional improvement 6 months after randomization; however, 30% of the patients who were assigned to physical therapy alone underwent surgery within 6 months. The results at 12 months were similar to those at 6 months.

7. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial.

Gabay C, Emery P, van Vollenhoven R, Dikranian A, Alten R, Pavelka K, Klearman M, Musselman D, Agarwal S, Green J, Kavanaugh A; ADACTA Study Investigators. Lancet. 2013 May 4;381(9877):1541-50.

One of the two head to head biologic studies in RA from 2013. Tocilizumab 8mg/kg iv 4 weekly (an IL-6 receptor signaling inhibitor) monotherapy was superior to adalimumab monotherapy 40mg sc 2 weekly for reduction of signs (DAS28 -3.3 in the Tocilizumab group and -1.8 in the Adalimumab group) and symptoms of rheumatoid arthritis in patients intolerant of Methotrexate at 24 weeks. The adverse event profiles of tocilizumab (12% SAE) and adalimumab(10% SAE)  were consistent with previous findings with raised LDL-cholestrol and ALT in the Tocilizumab group.

6. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial.

McInnes IB, Kavanaugh A, Gottlieb AB, Puig L, Rahman P, Ritchlin C,
Brodmerkel C, Li S, Wang Y, Mendelsohn AM, Doyle MK; PSUMMIT 1 Study Group. Lancet. 2013 Aug 31;382(9894):780-9. Epub 2013 Jun 13.

Introduces a new agent in the treatment of psoriatic arthritis. Ustekinumab (monoclonal antibody directed against IL-12/IL-23)  45mg or 90mg, significantly improved active psoriatic arthritis compared with placebo (ACR 20 achieved in 42.4% in the 45mg group, 49.5% in the 90mg group and 22.8% in the placebo group) and was maintained at week 52. The proportions of patients with adverse events were similar in the ustekinumab (41.8%) and placebo (42.0%) groups at week 16.

5. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomized placebo-controlled Phase 3 study.

Landewé R, Braun J, Deodhar A, Dougados M, Maksymowych WP, Mease PJ, Reveille JD, Rudwaleit M, van der Heijde D, Stach C, Hoepken B, Fichtner A, Coteur G, de
Longueville M, Sieper J. Ann Rheum Dis. 2014 Jan 1;73(1):39-47. Epub 2013 Sep 6.

This paper evaluates the efficacy and safety of certolizumab pegol (CZP) in patients with axial spondyloarthritis (axSpA), including patients with ankylosing spondylitis(AS) and non-radiographic axSpA (nr-axSpA). Patients with active axSpA were randomised  to placebo, CZP 200 mg every 2 weeks or CZP 400 mg every 4 weeks.

Baseline disease activity was similar between AS and nr-axSpA. At week 12, ASAS20 response rates were significantly higher in CZP 200 mg (57.7%) and CZP 400mg (63.6%) arms versus placebo (38.3). At week 24, combined CZP arms showed significant (p<0.001) differences in change from baseline versus placebo in BASFI (-2.28 vs -0.40), BASDAI (-3.05 vs -1.05), and BASMI (-0.52 vs
-0.07). Improvements were observed as early as week 1. Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA subpopulations. Adverse events were reported in 70.4% vs 62.6%, and serious adverse events in 4.7% vs 4.7% of All CZP versus placebo groups.

CZP rapidly reduced the signs and symptoms of axSpA, with no new safety signals observed compared to the safety profile of CZP in RA. Similar improvements were observed across CZP dosing regimens and in AS and nr-axSpA patients.

4. Efficacy of remission-induction regimens for ANCA-associated vasculitis.

Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Fessler BJ, Ding L, Viviano L, Tchao NK, Phippard DJ, Asare AL, Lim N, Ikle D, Jepson B, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh K, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Mueller M, Sejismundo LP,Mieras K, Stone JH; RAVE-ITN Research Group. N Engl J Med. 2013 Aug 1;369(5):417-27.

Provides choice and an alternative agent for the treatment of patients with severe ANCA-associated vasculitis. This paper shows 18-month efficacy of a single course of rituximab (375mg/m2 weekly for 4 weeks) as compared with conventional immunosuppression with cyclophosphamide (3 to 6 months) followed by azathioprine (12 to 15 months) in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.

There was non-inferiority of Rituximab (remission rate of 64% at 6 months, 48% at 12 months and 39% at 18 months) compared to continuous conventional immunosuppressive therapy (remission rate of 53%, 39% and 33% at 6,12 and 18 months respectively) for the induction and maintenance of remissions over the course of 18 months. There was no significant between-group difference in adverse events.

3. Therapies for active rheumatoid arthritis after methotrexate failure.

O'Dell JR, Mikuls TR, Taylor TH, Ahluwalia V, Brophy M, Warren SR, Lew RA,
Cannella AC, Kunkel G, Phibbs CS, Anis AH, Leatherman S, Keystone E; CSP 551 RACAT Investigators. N Engl J Med. 2013 Jul 25;369(4):307-18. Epub 2013 Jun 11.

A real world study addressing a common scenario in clinic. This study compares conventional therapy consisting of a combination of disease-modifying antirheumatic drugs (methotrexate, sulphasalazine, hydroxychloroquine) with biologic agents (etanercept) in patients with rheumatoid arthritis who have active disease despite treatment with methotrexate.

Triple therapy (sulfasalazine and hydroxychloroquine added to methotrexate) was noninferior to etanercept plus methotrexate in patients with rheumatoid arthritis who had active disease despite methotrexate therapy. Participants (27%) in both groups who switched therapies at 24 weeks had improvement after switching. The change between baseline and 48 weeks in the DAS28 was similar in the two groups (-2.1 with triple therapy and -2.3 with etanercept and methotrexate. There were no significant between-group differences in adverse events associated with the medications.

2. Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFα inhibitors and rituximab

Listing J, Kekow J, Manger B, Burmester GR, Pattloch D, Zink A, Strangfeld A. Ann Rheum Dis. 2013 Nov 29.

This paper investigates the impact of disease activity, the course of the disease, its treatment over time, comorbidities and traditional risk factors on
survival using data of the German biologics register RABBIT were used.

During 31 378 patient-years of follow-up, the standardised mortality ratio was 1.49. Patients with persistent, highly active disease (mean DAS28  >5.1) had a significantly higher  mortality risk (adjusted HR (HRadj)=2.43)  than patients with persistently low disease activity (mean DAS28<3.2). Poor function andtreatment with glucocorticoids > 5 mg/d was significantly associated with anincreased mortality, independent of disease activity. Significantly lower
mortality was observed in patients treated with tumour necrosis factor α (TNFα)
inhibitors (HRadj=0.64), rituximab (HRadj=0.57), or other biologics (HRadj=0.64), compared to those receiving methotrexate. To account for treatment termination in patients at risk, an HRadj for patients ever exposed to TNFα inhibitors or rituximab was calculated. This resulted in an HRadj of 0.77.

RA patients with long-standing high disease activity have increased risk of mortality. Effective control of disease activity  decreases mortality. TNFα inhibitors and rituximab seem to be superior to conventional DMARDs in reducing this risk.

1. Validation of the methotrexate-first strategy in patients with early, poor-prognosis rheumatoid arthritis: results from a two-year randomized, double-blind trial.

O'Dell JR, Curtis JR, Mikuls TR, Cofield SS, Bridges SL Jr, Ranganath VK, Moreland LW; TEAR Trial Investigators. Arthritis Rheum. 2013 Aug;65(8):1985-94.

Adds to our understanding of treatment strategies in RA (step up treatment vs. initial combination treatment). Patients were randomized to on of 4 groups: immediate treatment with MTX plus etanercept, immediate oral triple therapy (MTX plus sulfasalazine plus hydroxychloroquine), or step-up from MTX monotherapy to one of the combination therapies (MTX plus etanercept or MTX plus sulfasalazine plus hydroxychloroquine). All treatment arms included matching placebos.

At week 24, subjects in the 2 immediate-treatment groups demonstrated a greater reduction in the DAS28-ESR compared with those in the 2 step-up groups (3.6 versus 4.2). Between week  48 and week 102, subjects randomized to the step-up arms had a DAS28-ESR clinical response that was not different from that of subjects who initially received combination therapy, regardless of the treatment arm. At week 102, there was a statistically significant difference in the change in radiographic measurements from baseline between the group receiving MTX plus etanercept and the group receiving oral triple therapy (0.64 versus 1.69). This study demonstrates that initial MTX monotherapy with the option to step-up to combination therapy results in similar outcomes to immediate combination therapy. Approximately 30% of patients will not need combination therapy, and the 70% who will need it are clinically and radiographically indistinguishable from those who were randomized to receive immediate combination therapy.

Hope you've enjoyed reading my favourite 10 papers from 2013. 

Which were your favourite 10 papers? Share and let me know.


Views are my own. These are opinions and cannot replace the need to see your physician for review of your individual medical condition.

No comments:

Post a Comment