Dynamic Study Of Effect Of Low Dose Infliximab In Ankylosing Spondylitis

Objectives: To study the effect of low dose infliximab in patients with ankylosing spondylitis(AS) in3different aspects simultaneously. The first is clinical disease activity of AS measuredby Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath AnkylosingSpondylitis Metrology Index (BASMI), the second is its relationship with routine laboratoryparameters predicting the disease activity, like Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), platelet etc and the third is serum level of cytokines like TNF-α and IL-6.Method: Thirty-four patients with AS treated with infliximab were included in this longitudinalcohort study. All patients fulfilled the modified New York criteria for AS. Low dose infliximabwas given intravenously (3mg/kg body weight) at0,2,6and every8weeks thereafter for aperiod of22weeks. Clinical disease activity was assessed by BASDAI score and BASMI scoreand clinical improvement was recorded according to Bath Ankylosing Spondylitis DiseaseActivity Index20%(BASDAI20), Bath Ankylosing Spondylitis Disease Activity Index50%(BASDAI50) and Bath Ankylosing Spondylitis Disease Activity Index70%(BASDAI70).Laboratory measures like ESR, CRP, total platelet count and serum albumin were recorded ateach visit. Serum TNF-α level and IL-6were analyzed in13patients for4visits. Radiologicalassessment was done by computed tomography (CT) scan of sacro-iliac joint before the patientstarted therapy. Therapeutic safety of the drug was monitored at each visit by assessing completeblood count, liver function test and renal function test.Result: Thirty-four patients were enrolled in the study. The mean age of the patients was32.5years and mean weight was72.2kg.88.2%of the patients were male and11.8%patients werefemale.41.2%(14/34) of the patients were smoker. All the patients tested positive for HLA-B27.CT scan of sacro-iliac joint revealed33.3%patients with grade IV sacroiliitis bilaterally,48.5%patients with grade III sacroiliitis bilaterally and18.2%patients with grade II sacroiliitisbilaterally. The mean duration of morning stiffness experienced by the patients was32minutes.At baseline45.5%patients had BASDAI score≥4; the mean BASDAI score at baseline was4.2.The mean patient’s global assessment of pain on visual analogue scale (Pt VAS) at baseline was6.4. The mean ESR, CRP, total platelet count and serum albumin at the baseline were30.9mm in1st hr,30.1mg/L,280x109/L and38.4g/L, respectively. Baseline levels of ESR and CRP were elevated in82.4%and70.6%of patients, respectively. In17.6%of patients none of thesemarkers was elevated and in70.6%of patients both of these markers were elevated at baseline.The mean baseline serum TNF-α and IL-6level were190.2ng/L and98.9ng/L, respectively.Serum TNF-α and IL-6level were significantly high in AS patients compared to that of healthycontrol (p=0.027, p=0.005, respectively). Serum IL-6was correlated with baseline CRP(r=0.684,p=0.010) and serum TNF-α level (r=0.885, p=0.000). There was significant correlation betweenCRP and Pt VAS (r=0.401, p=0.021), between duration of morning stiffness and Pt VAS(r=0.499, p=0.003) and BASDAI score (r=0.525, p=0.002) at baseline. Disease duration was alsopositively correlated with duration of morning stiffness (r=0.479, p=0.006), BASDAI score(r=0.362, p=0.049) and BASMI score (r=0.394, p=0.028) at baseline.Efficacy assessment at week6revealed significant improvement in mean BASDAI score (4.3versus1.4, p=0.000), BASMI (3.7versus2.9, p=0.001), Pt VAS (6.4versus2.5, p=0.000), aswell as in duration of morning stiffness (32.2versus7.6minutes, p=0.000) compared to baseline.There was significant improvement seen in ESR (28.4versus9.0mm in1sthr, p=0.000), CRP(32.2versus8.7mg/L, p=0.003), platelet count (278versus223x109/L, p=0.002) andsignificant increase in serum albumin level (37.8versus42.2g/L, p=0.010). BASDAI20,BASDAI50and BASDAI70response at week6were seen in93.3%,76.9%and53.8%ofpatients, respectively. There was significant correlation between BASDAI50response at6weekand baseline ESR (r=0.469, p=0.016), baseline CRP (r=0.392, p=0.048) and disease duration(r=0.436, p=0.029). Elevated CRP at the baseline had the highest predictive value (94.4%) forthe BASDAI50response at6week followed by serum IL-6level which was81.8%.Efficacy assessment at week22showed further significant improvement in BASDAI score (4.0versus0.8, p=0.006) and Pt VAS (4.5versus2.1, p=0.015) when compared to baseline. Durationof morning stiffness, ESR, CRP, total platelet count and serum albumin were also decreased butnot significantly compared to the baseline values (43.1versus7.5minutes, p=0.051;19.7versus16.1mm in1sthr, p=0.348;21.8versus10.7mg/L, p=0.322;296versus270x109/L, p=0.426;40.4versus40.1g/L, p=0.881; respectively). BASDAI20, BASDAI50and BASDAI70responseat week22were seen in85.7%,85.7%and57.1%of patients, respectively.Although statistically not significant but there was improvement in BASDAI score, Pt VAS andduration of morning stiffness at22week compared to that of6week (2.5versus0.9, p=0.115;3.2versus2.3, p=0.058;18.3versus8.3minutes, p=0.275; respectively). BASMI was significantly improved at week22compared to week6(3.4versus2.7, p=0.047). Mean ESR andCRP was elevated at22weeks compared to that of6weeks but it was not significantly elevated(7.3versus9.8mm in1sthr, p=0.385;3.9versus11.1mg/L, p=0.1, respectively).Conclusion: TNF-α and IL-6may play an important role in pathology of AS. The inflammatorymarkers like ESR and CRP and serum cytokines like IL-6at baseline serve as a powerful tool notonly for monitoring the efficacy of infliximab, but also for the selection of AS patients with ahigh likelihood of responding to the treatment. Most of the patients with AS response as rapidlyas2weeks with the administration of the TNF-α inhibitor, infliximab, at a low dose of3mg/kgand show a durable response for about6months. Serum cytokines levels reflect as an earlybiological indicator for inadequacy of treatment so starting at a low dose of infliximab and thenincreasing, either in the dose of infliximab from3mg to5mg, or decreasing in the maintenancedose duration from8weekly to4-6weekly when indicated, seems an efficient and sensible wayin clinical practice as most of the patients attain significant response with low dose infliximaband in addition, using low dose infliximab has a significant economic implication.