A predictive model for remission and low disease activity in patients with established rheumatoid arthritis receiving TNF blockers

Abstract

The objective of this study was to identify predictors for remission or low disease activity (LDA) in established rheumatoid arthritis (RA) at 12 months of anti-TNF-α therapy. We have performed a prospective observational study in 90 consecutive patients with active RA receiving TNF-α inhibitors. Baseline and standard assessments were done every 3 months, including individual parameters (clinical and biological) and composite activity scores (28-joint disease activity score, DAS28). The primary outcome measure was DAS28-based EULAR response criteria. The multivariate logistic regression was used to analyze the association between disease activity and several RA baseline characteristics. Of the RA, 78.8 % was classified as good responders based on the EULAR-DAS28 criteria, 44.4 % RA achieving remission (DAS28 ≤ 2.6) and 34.4 %, LDA (DAS28 ≤ 3.2). Parameters associated with an increased likelihood of remission and LDA were initial DAS28-erythrocyte sedimentation rate ≤ 7 (odds ratio (OR) 3.3, 95 % confidence interval (CI) 2.03-5.81; OR 1.8, 95 % CI 1.09-6.68), Health Assessment Questionnaire Disability Index ≤ 2 (OR 7.0, 95 % CI 1.56-31.91; OR 1.3, 95 % CI 1.03-5.79), C-reactive protein level ≤ 20 mg/l (OR 1.5, 95 % CI 0.29-8.22; OR 0.5, 95 % CI0.08-2.97), rheumatoid factor ≤ 20 IU/ml (OR 18.9, 95 % CI 10.79-38.36; OR 32.9, 95 % CI 4.03-269), anti-cyclic citrullinated peptide antibodies ≤ 40 IU/ml (OR 3.5, 95 % CI 0.67-18.19; OR 1.2, 95 % CI 1.02-1.59), concurrent prednisolone (OR 0.2, 95 % CI 0.05-0.36; OR 0.2, 95 % CI 0.06-0.63), methotrexate or leflunomide (OR 1.6, 95 % CI 1.2-13.53; OR 2.9, 95 % CI 1.20-4.36). A predictive matrix for remission and LDA in established active RA patients receiving TNF-α inhibitors was proposed. Further studies are necessary to confirm the value of such matrix in particular RA settings, leading to optimization of the use of anti-TNF-α therapy.

FCGR2A/FCGR3A Gene Polymorphisms and Clinical Variables as Predictors of Response to Tocilizumab and Rituximab in Patients With Rheumatoid Arthritis

“…There are numerous therapeutic options for treating a candidate rheumatoid arthritis patient with bDMARDs, and therefore predictors of response are required to select the treatment to which the patient will best respond. The clinical predictors of response for TNFi are male sex, age ≤ 54 years old at the start of TNFi therapy, high baseline DAS28, concomitant treatment with cDMARDs, and negative or low levels of CRP . Regarding other biochemical predictors, 2 meta‐analyses (5561 and 5703 rheumatoid arthritis patients) did not find any association between the values of RF and anti‐CCP and response to TNFi therapy …”

“…The clinical predictors of response for TNFi are male sex, age ࣘ 54 years old at the start of TNFi therapy, high baseline DAS28, concomitant treatment with cDMARDs, and negative or low levels of CRP. [13][14][15]44 Regarding other biochemical predictors, 2 meta-analyses (5561 and 5703 rheumatoid arthritis patients) did not find any association between the values of RF and anti-CCP and response to TNFi therapy. 20,21 In our study, the multivariate analysis demonstrated that patients treated with tocilizumab reported higher response when they were bDMARD naive, when tocilizumab was administered subcutaneously, when a smaller number of previous biological therapies had been administered, when they were younger at diagnosis and beginning of treatment, and when baseline values of DAS28, NTJ, and NSJ were higher.…”

“…Interindividual variability in bDMARD response is influenced by clinical, biochemical, and genetic factors. Clinical factors associated with better response (EULAR response/remission) to TNFi have been reported in numerous studies: being male, younger age at beginning of treatment, concomitant treatment with csDMARDs, low level of C‐reactive protein (CRP), and a high baseline value of DAS28 . Two baseline factors were associated with greater response to rituximab: a high DAS28 value and a smaller number of previous biological therapies .…”

Guidelines for biomarkers in autoimmune rheumatic diseases - evidence based analysis

“…Higher anti-CCP and RF concentrations resulted associated with greater disease activity over time along with lower chance to achieve sustained remission in men with established RA mainly under csDMARDs background [32,33]. Similarly, baseline low RF and anti-CCP levels (arbitrarily chosen by the authors) were independently predictive of clinical remission and low disease activity achievement at 12 months in 90 Romanian RA patients starting their first TNFi.…”

Is Male Rheumatoid Arthritis an Occupational Disease? A Review

“…It is well established that cigarette smoking reduces the clinical response to both methotrexate and tumour necrosis factor (TNF) inhibitors [ 89 , 90 ]. Cigarette smoking is strongly associated with the titres of RF [ 91 ], and it is noteworthy that a RF titre < 20 IU/ml was highly predictive for remission or low disease activity in RA patients with established disease receiving TNF inhibitors [ 92 ]. In this study RA patients with a RF titre < 20 IU/ml were significantly more likely (OR 18.9, 95% CI 10.79-38.36) to be in remission at 12 months than RA patients with a RF titre >20 IU/ml.…”