RESEARCH - Association of RF and anti-CCP positivity, but not SE or PTPN22, with anti-TNF response in RA

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Ann Rheum Dis. 2009 Jan;68(1):69-74.

Association of rheumatoid factor and anti-cyclic citrullinated peptide

positivity, but not carriage of shared epitope or PTPN22

susceptibility variants, with anti-tumour necrosis factor response in

rheumatoid arthritis.

Potter C, Hyrich KL, Tracey A, Lunt M, Plant D, Symmons DP, Thomson W,

Worthington J, Emery P, AW, AG, Isaacs J, Barton A;

BRAGGSS.

Collaborators (99)

Crisp AJ, Gaston JS, Hall FC, Hazleman BL, Jenner JR, Ostor A,

Silverman B, Speed C, Armstrong D, Chuck AJ, Hailwood S, Badcock LJ,

Deighton CM, O'Reilly SC, Regan MR, Snaith, Summers GD, RA,

Lambert JR, s R, Wilkinson C, Hamilton J, Heycock CR, CA,

Saravanan V, Rees DH, RB, Chalam SV, Mulherin D, Price T,

Sheeran T, Bukhari M, Dodds WN, Halsey JP, Gaffney K, Macgregor AJ,

Marshall T, Merry P, DG, on B, Pattrick M, Snowden HN,

Sheehan NJ, NE, Hull RG, Ledingham JM, Mccrae F, Shaban MR,

AL, Buckley CD, Carruthers DC, Elamanchi R, Gordon PC,

Grindulis KA, Khattak F, Raza K, Situnayake D, Akil M, Amos R, Bax DE,

Till S, G, Winfield J, e F, Fordham JN, Plant MJ, Tuck,

Abernethy VE, Dawson JK, Lynch M, Bingham S, Emery P, A,

Birrell F, Crook P, HE, Griffiths B, Griffiths ID, Grove ML,

Isaacs JD, Kay L, Myers A, Platt PN, DJ, Bowman, Jobanputra P,

Jubb RW, Rankin EC, Carpenter EH, Dawes PT, Hassell A, Hay EM, Kamath

S, Packham J, Shadforth MF, Donnelly SP, Doyle D, Hakim A, Lanham JG.

Arthritis Research Campaign Epidemiology Unit, University of

Manchester, Manchester, UK.

OBJECTIVE: To determine whether rheumatoid factor (RF), anti-cyclic

citrullinated peptide (CCP) antibodies, or carriage of shared epitope

(SE) and PTPN22 genetic susceptibility variants predict response to

therapy in patients with rheumatoid arthritis (RA) treated with

anti-tumour necrosis factor (TNF) agents.

METHODS: UK-wide multicentre collaborations were established to

recruit a large cohort of patients treated with anti-TNF drugs for RA.

Serum RF, anti-CCP antibody and SE status were determined using

commercially available kits. PTPN22 R620W genotyping was performed by

Sequenom MassArray. Linear regression analyses were performed to

investigate the role of these four factors in predicting response to

treatment by 6 months, defined as the absolute change in 28-joint

Disease Activity Score (DAS28).

RESULTS: Of the 642 patients analysed, 46% received infliximab, 43%

etanercept and 11% adalimumab. In all, 89% and 82% of patients were RF

and anti-CCP positive, respectively. Patients that were RF negative

had a 0.48 (95% CI 0.08 to 0.87) greater mean improvement in DAS28

compared to patients that were RF positive. A better response was also

seen among patients that were anti-CCP negative. No association was

demonstrated between drug response and SE or PTPN22 620W carriage.

CONCLUSION: The presence of RF or anti-CCP antibodies was associated

with a reduced response to anti-TNF drugs. However, these antibodies

only account for a small proportion of the variance in treatment

response. It is likely that genetic factors will contribute to

treatment response, but these do not include the well established RA

susceptibility loci, SE and PTPN22.

PMID: 18375541

http://www.ncbi.nlm.nih.gov/pubmed/18375541

Not an MD