Top Clinical Articles in Rheumatology from 2012

Clinical Trials

►  van Vollenhoven RF, Fleischmann R, Cohen S, et al, Tofacitinib or Adalimumab(Drug information on adalimumab) versus Placebo in Rheumatoid Arthritis. N Engl J Med (2012) 367:508-519.

Tofacitinib is effective in RA. In a 12-month, phase 3 randomized crossover trial involving 717 RA patients who were receiving stable doses of methotrexate(Drug information on methotrexate), ACR response rates at month 6 were significantly higher among patients receiving either drug than among those on placebo. HAQ-DI and DAS28 scores were also significantly better in the treatment groups. Tofacitinib was associated with more adverse events than adalimumab, however, including increases in lipoprotein fractions, decreases in neutrophil counts and, in two patients, pulmonary tuberculosis.

►  Kingsley GH, Kowalczyk A, Taylor H, A randomized placebo-controlled trial of MTX in PsA. Rheumatology (2012) 51(8): 1368-1377.

This randomized trial with negative results raised the question whether methotrexate should continue to be used for psoriatic arthritis. See the companion editorial, reached via a hyperlink at the end of the text.

►  Yazici Y, Curtis JR, Ince A, et al, Efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis and a previous inadequate response to disease-modifying antirheumatic drugs: the ROSE study
Ann Rheum Dis (2012) 71:198-205 .

A randomized double-blind placebo-controlled trial of tocilizumab in RA patients who failed to respond to DMARDs showed significant improvements in the treatment group, starting as soon as the first week after tocilizumab was added to their DMARD medication.

►  Tak PP, Rigby W, Rubbert-Roth A, et al, Sustained inhibition of progressive joint damage with rituximab(Drug information on rituximab) plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE
Ann Rheum Dis. (2012) 71: 351–357.

After two years, patients in this randomized trial who received rituximab rather than placebo in addition to their existing methotrexate treatment for early rheumatoid arthritis continued to show reduced signs of joint damage and sustained improvements in clinical, radiographic, and functional outcomes.

►  van Vollenhoven RF, Petri MA, Cervera R, et al, Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response
Ann Rheum Dis (2012) 71:1343-1349.

Analysis of phase 3 results from the BLISS trial of belimumab for lupus established that adding the drug to standard therapy will benefit patients who have higher disease activity, anti-dsDNA positivity, low complement or were being treated with corticosteroids.

[Drawn from a presentation at the October meeting of the American College of Rheumatology, this list was compiled too early to include the following important reports published concurrently in late December.]

►  De Benedetti F, Brunner HI, Ruperto N, et al, Randomized trial of tocilizumab in Systemic Juvenile Idiopathic Arthritis
New Engl J Med (2012) 367:2385-2395.

►   Ruperto N, Brunner HI, Quartier P, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis.
N Engl J Med (2012) 367:2396-2406.

An intractable rheumatic disease of childhood with no good option for treatment suddenly has two. In separate collaborative trials of juvenile idiopathic arthritis, he interleukin-1 inhibitor canakinumab and the interleukin-6 inhibitor tocilizumab prove similarly effective against JIA assessed for the same outcome, the adapted ACR JIA response measure.

Observational Studies

►  Grayson PC, Maksimowicz-McKinnon K, Clark TM, et al, Distribution of arterial lesions in Takayasu's arteritis and giant cell arteritis
Ann Rheum Dis (2012) 71:1329-1334.

Boston University researchers noted striking similarities between arteriographic studies of Takayasu's and GCA, leading to the suggestion that the two conditions are entities along the same spectrum of disease.

►  Bacani AK, Gabriel SE, Crowson CS, et al, Noncardiac vascular disease in Rheumatoid Arthritis: Increase in Venous Thromboembolic Events?
Arthritis Rheum (2012) 64:53-61.

Vigilance about cardiovascular disease risk among RA patients should extend to the risk of thromboembolism. A 27-year longitudinal study of the (largely Caucasian) general population surrounding the Mayo Clinic in Minnesota revealed that individuals in whom RA developed had an increased incidence of venous thromboembolism, but this did not translate to higher rates of cerebrovascular or peripheral arterial events. These rates did not change notably over the lengthy period of observation.

Treatments

►  Judge A, Arden NK, Cooper C, et al, Predictors of outcomes of total knee replacement surgery Rheumatology (Oxford) (2012) 51:1804-1813.

Preoperative severity of disease and anxiety or depression were the most potent predictors of postoperative outcomes for total knee replacement, in this prospective study of a cohort in London, England. Patients with rheumatoid arthritis fared better after surgery than those with osteoarthritis of the knee.

►  Stamp LK, Taylor WJ, Jones PB, et al, Starting dose is a risk factor for allopurinol(Drug information on allopurinol) hypersensitivity syndrome: A proposed safe starting dose of allopurinol
Arthritis Rheum (2012) 64:2529-2536.

A retrospective case-control study of patients in whom allopurinol sensitivity developed suggests starting the drug at a dose of 1.5 mg per unit of estimated GFR and increasing the dose gradually to allow timely recognition if hypersensitivity arises.

►  Bharat A, Xie F, Baddley JW, et al, Incidence and risk factors for Progressive Multifocal Leukoencephalopathy among patients with selected rheumatic diseases
Arthritis Care Res (2012) 64:612-615.

A population-based study of more than 2 million patients with rheumatic disorders show that the incidence of PML is very low, at 0.2 per 100,000 patients who do not have HIV or malignancy.



►  Soliman MM, Hyrich KL, Lunt M, et al, Rituximab or a second anti-tumor necrosis factor therapy for rheumatoid arthritis patients who have failed their first anti-tumor necrosis factor therapy? Comparative analysis from the British Society for Rheumatology Biologics Register
Arthritis Care Res(2012)64:1108-1115 .
A registry study involving 1,328 RA patients who switched medications after unsatisfactory results from a first TNF inhibitor lent support for trying rituximab next, rather than a different TNF inhibitor.

Translational Research


►  Steinman AJ, Gladman DD, Ibañez D, and MB Urowitz. Outcomes in patients with systemic lupus erythematosus with and without a prolonged serologically active clinically quiescent period
Arthritis Care Res (2012) 64:511-518.

Is treatment justified for patients with SLE whose disease undergoes a sustained quiescent period? This case-control study involving 55 patients with quiescent disease observed over at least three years supports a strategy of observant waiting.


►  Muro Y, Sugiura K, Hoshino K, and M Akiyama. Disappearance of anti-MDA-5 autoantibodies in clinically amyopathic DM/interstitial lung disease during disease remission
Rheumatology (Oxford) (2012) 51:800-804.

A longitudinal study suggests that autoantibodies against melanoma differentiation-associated gene 5 may prove a useful marker to monitor disease status in amyopathic dermatomyositis with comorbid ILD.


►  Gottenberg JE, Dayer JM, Lukas C, et al, Serum IL-6 and IL-21 are associated with markers of B cell activation and structural progression in early rheumatoid arthritis: results from the ESPOIR cohort
Ann Rheum Dis (2012) 71:1243-1248.

Looking to identify patterns of serum cytokines that correlates with disease status in early rheumatoid arthritis, these researchers found that increases in serum IL-6 and IL-21 correlated with markers of B-cell activaion, and IL-6 is associated with radiographic progression.


►  Nielsen SF, Bojesen SE, Schnohr P, and BG Nordestgaard. Elevated rheumatoid factor and long term risk of rheumatoid arthritis: a prospective cohort study
BMJ (2012) Sep 6;345:e5244.

This sets out a case for rheumatoid factor screening in the general population. A study involving nearly 10,000 adults in Copenhagen found as much as a 26-fold greater long term risk of rheumatoid arthritis among individuals with elevated rheumatoid factor, and about one-in-three odds of being diagnosed with RA within a decade.


►  Mammen AL, Gaudet D, Brisson D, et al, Increased frequency of DRB1*11:01 in anti-hydroxymethylglutaryl-coenzyme A reductase- associated autoimmune myopathy
Arthritis Care Res (2012) 64:1233-1237.

This study finds a link between an HLA marker and the occurrence of autoimmune myopathy among Caucasians and African-Americans. The findings suggest a "mechanistic link" to statin exposure.

Other Reports of Interest


►  Laine J, Uotila T, Antonen J, et al, Joint symptoms after a large waterborne gastroenteritis outbreak--a controlled, population-based questionnaire study
Rheumatology (Oxford) (2012) 51:513-518.

Residents of a Finnish town were about three times as likely to report joint pain if they lived in regions exposed to a 2007 waterborne gastroenteritis than if they did not. Even those people who were exposed but did not develop gastroenteritis were more likely to report joint pain.


►  Antohe JL, Bili A, Sartorius JA, et al, Penile alterations with severe sperm abnormalities in antiphospholipid syndrome associated with systemic lupus erythematosus
Clin Rheumatol Epub ahead of print Sept 2012 DOI: 10.1007/s10067-012-2083-4.

Patients who have lupus complicated with antiphospholipid syndrome should have penile examinations if they experience fertility problems, say these researchers. They report not only penile morphological abnormalities associated with erectile dysfunction but also reductions in sperm count and sperm motility, particularly among patients who have taken cyclophosphamide(Drug information on cyclophosphamide).

(Adapted from an invited presentation by David A. Isenberg MD at the 2012 annual meeting of the American College of Cardiology. Dr. Isenberg is professor of rheumatology at University College Hospital London.)