| First author | Type of study | Treatment/duration | Changes in lipid parameters, lipid ratios and/or inflammation markers | Comments |
| Treatment duration <6 months | ||||
| Popa32 | Prospective, single-centre, consecutive patient studyThe Netherlands | 3 mg/kg infliximab, weeks 0, 2; DMARDs and oral corticosteroids were allowed (prednisone <10 mg/day)/2 weeks (n = 67 patients with RA) | TC (mmol/l): ↑;† 5.55,* mean Δ1.07 mmol/l (mean values)HDL (mmol/l): ↑;† 1.37,* mean Δ1.08 mmol/l (mean values)LDL (mmol/l): ↑;† 3.54,* mean Δ1.08 mmol/l (mean values)TG (mmol/l): ↔; 1.50* (mean value)TC/HDL: ↔; 4.19* (mean value)LDL/HDL: ↔; 2.72* (mean value) | All participants had active RA (DAS >3.2) at baseline; patients taking lipid-lowering drugs were excluded. |
| Allanore31 | Prospective, consecutive patient studyFrance | 3 mg/kg infliximab, weeks 0, 2 and 6 + 7.5–20 mg MTX, weekly/6 weeks (n = 59 patients with RA) | TC (mmol/l): ↑;† 5.0,* 5.9§ (mean values)HDL (mmol/l): ↑;† 1.3,* 1.4§ (mean values)LDL (mmol/l): ↑;† 3.0,* 3.6§ (mean values)TG: ↔ (mean value)TC/HDL: ↔ (mean value)LDL/HDL: ↔ (mean value)CRP (mg/l): ↓;† 29.8,* 7.6§ (mean values)ESR (mm/h): ↓;† 30.7,* 18.1§ (mean values) | Patients were refractory to DMARD therapy, including MTX. Patients excluded if suffering from conditions that affect lipid profiles such as DM, hypothyroidism, chronic liver disease, alcoholism, Cushing syndrome, obesity (BMI >30 kg/m2).Patients taking lipid-modifying drugs were excluded. |
| Vis34 | Prospective, single-centre, consecutive patient studyThe Netherlands | 3 mg/kg infliximab, weeks 0, 2 and 6/6 weeks (n = 69 patients with RA) | TC (mmol/l): ↑;† 5.17,* 5.52§HDL (mmol/l): ↑;† 1.47,* 1.59§TC/HDL: ↔ (mean value) | All participants had active RA (DAS >3.2) at baseline. Thirty-two patients were using corticosteroids at baseline; of which 19 maintained a stable dose and 13 reduced dose during study period. |
| Peters35 | Prospective, single-centre, consecutive patient studyThe Netherlands | 3 mg/kg infliximab, weeks 0, 2 and 6; MTX (15 mg/week) and prednisone were allowed (<10 mg/day)/6 weeks (n = 80 patients with RA) | TC (mmol/l): ↑;† 4.79,* 5.08§ (median values)HDL (mmol/l): ↑;† 1.46 mmol/l,* 1.61§ (mean values)TG (mmol/l): ↑;† 1.26 mmol/l ,* 1.39§ (median values)TC/HDL: ↓;† 3.42,* 3.20§ (median value) | At baseline, 5% of patients used statins and 2% had DM. At study start, 96% of patients used concomitant MTX (15 mg/week) and 44% used prednisone. Following 6 weeks treatment and compared with baseline, mean apo A-I levels were increased (1.58* vs 1.70§ mmol/l), while apo B levels were unchanged, leading to a decrease in the mean apo B:apo A-I ratio (0.62* vs 0.58§). |
| Sattar17 | Prospective, multicentre, double-blind, placebo-controlled, randomised studyUK | 50 mg onercept, 3 times weekly/12 weeks (n = 42 patients with psoriatic arthritis) | TC (mmol/l): ↔; 5.37,* (mean value)HDL (mmol/l): ↔; 1.17,* (mean value)TG (mmol/l): ↔; 1.82,* (mean value)Lp(a) (mg/dl): ↓;† 30.6,* Δ2.02 (mean value)CRP (mg/l): ↓;† 14.0,* Δ−12.83 (median value, mean change) | All patients had active plaque psoriasis and active psoriatic arthritis and had experienced failure with at least one psoriatic treatment and at least one DMARD. Most patients were overweight; mean BMI ≈28 kg/m2. At baseline, two patients were taking statins. In patients taking 100 mg onercept, apo A-I levels were increased versus placebo (mean change; 3.9 vs −5.6 mg/dl, respectively), apo B levels were increased versus placebo (mean change; 6.3 vs −0.4 mg/dl, respectively), sex hormone binding globulin levels were increased versus placebo (mean change; 4.3 vs −1.3 mmol/l, respectively) and homocysteine levels were decreased versus placebo (mean change; −1.72 vs 0.34 μmol/l, respectively). In a subset of patients receiving 100 mg onercept, fibrinogen levels were reduced versus placebo (mean change; −2.02 vs −0.68 gm/l). |
| 100 mg onercept, 3 times weekly/12 weeks (n = 42 patients with psoriatic arthritis) | TC (mmol/l): ↔ 5.24,* (mean value)HDL (mmol/l): ↔1.10,* (mean value)TG (mmol/l): ↑;† 1.65,* Δ0.09 (mean value, mean change)Lp(a) (mg/dl): ↓;† 28.3,* Δ−3.11‡ (mean value, mean change)CRP (mg/l): ↓;† 12.5,* Δ–13.93‡ (median value, mean change) | |||
| Soubrier54 | Prospective, single centre, studyFrance | 40 mg adalimumab, every other week or 3 mg/kg infliximab, weeks 0, 2, 6 and 8 or 25 mg etanercept, twice weekly/14 weeks (n = 29 patients with RA) | TC (mmol/l): ↔;† 5.65*HDL (mmol/l): ↔;† 1.92*LDL (mmol/l): ↔;† 3.41*TG (mmol/l): ↔;† 1.40*TC/HDL: ↔;† 3.13* | After 14 weeks of treatment, levels of apo A-I, apo B and the apo A-I:apo B ratio were also unchanged compared with baseline (1.92* g/l, 1.126*g/l, 0.58,* respectively). |
| Tam33 | Prospective, single-centre, consecutive patient studyChina | 3 mg/kg infliximab, weeks 0, 2, 6 and 14; NSAIDs, MTX and prednisolone (⩽10 mg/day) could be continued/14 weeks (n = 19 female patients with RA) | TC (mmol/l): ↑;† 4.62,* 5.22§ (mean values)HDL (mmol/l): ↑;† 1.52,* 1.67§ (mean values)LDL (mmol/l): ↑;† 2.68,* 3.0§ (mean values)TG (mmol/l): ↑;† 0.93,* 1.22§ (mean values)TC/HDL: ↔;† 3.25* (mean value)LDL/HDL: ↔;† 2.0* (mean value)CRP (mg/l): ↓;† 16.3,* 3.7§ (median values)ESR (mm/h): ↓;† 69,* 36§ (median values) | Patients were required to have active RA despite at least 3 months treatment with at least 12.5 mg MTX per week. No patient was taking known lipoprotein metabolism-modifying drugs. Patients were excluded from study if taking DMARDs other than MTX. Patients had no history of DM or hypercholesterolaemia. One patient was taking 7.5 mg/day prednisolone.After 14 weeks treatment, median apo B levels were increased versus baseline (90.4 vs 107.0 g/l, respectively), but the mean LDL:apo B ratio was unchanged (0.031*).Changes in CRP were not associated with changes in metabolic variables. |
| Dahlqvist39 | Prospective, single-centre, consecutive patient studySweden | 3 mg/kg infliximab, weeks 0, 2, 6 and then every 8 weeks; continuation of DMARDs and corticosteroids allowed/3 months (n = 52 patients with RA) | TC: ↑¶HDL: ↑¶LDL: ↑¶TG: ↑¶TC/HDL: ↑¶LDL/HDL: ↑¶ | Patients were required to have RA that was not controlled by DMARD treatment. |
| Treatment duration ⩾6 months | ||||
| Kiortsis37 | Single-centre, consecutive patient studyGreece | 3 mg/kg infliximab, week 0, 2, 6 and then every 8 weeks + MTX or cyclosporine A and prednisone (5 mg/day)/6 months (n = 82 patients with RA) | TC (mg/dl): ↔;† 211*HDL (mg/dl): ↔;† 53*LDL (mg/dl): ↔;† 134 *TG (mg/dl): ↑;† 113,* 126§TC/HDL: ↔† | All patients with RA had active disease and were refractory or intolerant to two DMARDs. Patients were excluded from study if they had history/presence of malignant disease, liver/kidney abnormalities, DM, major complicating diseases such as amyloidosis, heart or lung disease, endocrine or metabolic disorders, or a positive tuberculin skin test or abnormal chest X-ray. Patients were also excluded if taking lipid-modifying drugs. During the study, 94% of patients took MTX and 6% took cyclosporine. Patients with ankylosing spondylitis were also examined in this study (data not reported) |
| Seriolo38 | Prospective, single-centre, consecutive patient studyItaly | 3 mg/kg infliximab, week 0, 2, 6 and then every 8 weeks or 25 mg etanercept, twice weekly or adalimumab, 40 mg every other week; 10 mg MTX, weekly (permitted) + <10 mg prednisone (daily) (permitted)/6 months (n = 34 female patients with RA) | TC (mg/dl): ↑;† 168,* 197§ (mean values)HDL (mg/dl): ↑;† 34,* 38§ (mean values)TG (mg/dl): ↔;† 126* (mean value)Lp(a) (mg/dl): ↔;† 31* (mean value)TC/HDL: ↔;† 3.9* (mean value) | At baseline, patients had active RA DAS28 >3.2 and had been on stable MTX and prednisone treatment for 3 months. Overall BMI at baseline was 25.7 kg/m2 and 21% of patients had hypertension. |
| Spanakis40 | Prospective, single-centre, consecutive patient studyGreece | 3 mg/kg infliximab, week 0, 2, 6 and then every 8 weeks + ongoing stable DMARDs and corticosteroids (<10 mg/day)/6 months (n = 60 patients with RA, ankylosing spondylitis or psoriatic arthritis) | TC (mg/dl): ↔;† 203,* 211§ (mean values)HDL (mg/dl): ↑;† 49,* 52§ (mean values)LDL (mg/dl): ↔;† 132* (mean values)TG (mg/dl): ↔;† 109* (mean values)TC/HDL: ↔;† 4.4* (mean values)LDL/HDL: ↔;† 2.9* (mean values)CRP (mg/dl): ↔;† 2.38* (mean values)ESR (mm/h): ↓;† 41,* 30§ (mean value) | All patients were taking infliximab because of ongoing disease activity despite DMARDs and comprised: 24 with RA, 26 with ankylosing spondylitis, and 10 with psoriatic arthritis. |
| Saiki26 | Retrospective, single-centre studyJapan | Infliximab, week 0, 2, 6 and then every 8 weeks + 5 mg prednisolone, daily (patients with active RA) + 6 mg/m2 MTX, weekly/6 months (n = 32 patients with RA) | TC (mg/dl): ↑; 167,* 214§TG (mg/dl): ↑; 92,* 207§CRP (mg/dl): ↓; 4.5,* 0.3§ | Patients with refractory RA (n = 32) with a successful outcome (DAS28 score <2.6) after 6 months infliximab treatment were retrospectively selected. None of the patients had a history of DM nor were taking lipid-metabolism-modifying drugs. Patients excluded: those with nephrotic syndrome, liver/kidney disorders, alcoholism, or thyroid abnormalities. No patients had acute infection, syphilis, ischaemic heart disease, malignant neoplasm, iatrogenic Cushing’s disease, or were overweight. |
| Allanore31 | As above | 3 mg/kg infliximab, weeks 0, 2, 6 and then every 8 weeks + 7.5–20 mg MTX, weekly/30 weeks (n = 59 patients with RA) | TC (mmol/l): ↑;† 5.0,* 6.0§ (mean values)HDL (mmol/l): ↑;† 1.3,* 1.5§ (mean values)LDL (mmol/l): ↑;† 3.0,* 3.5§ (mean values)TG: ↔;† 1.6* (mean value)TC/HDL: ↔;† 4.3*LDL/HDL: ↔;† 2.6*CRP (mg/l): ↓;† 29.8,* 6.4§ (mean values)ESR (mm/h): ↓;† 30.7,* 16.5§ (mean values) | As aboveAfter 30 weeks treatment, there was an inverse correlation between CRP and HDL and no correlation between the lipid parameters or lipid ratios and inflammation markers (CRP or ESR). |
| Garcês43 | Consecutive patient study | Infliximab or etanercept (doses not reported)/1 year (n = 65 patients; 30 with RA, 29 with ankylosing spondylitis and 6 with psoriatic arthritis) | TC (mg/dl): ↑;† 180,* 198§ (mean values)HDL (mg/dl): ↔;† 57,* 60§ (mean values)LDL (mg/dl): ↑;† 105,* 123§ (mean values)TG (mg/dl): ↔;† 102,* 112§ (mean values)TC/HDL: ↔;† 3.4,* 3.5§LDL/HDL: ↑;† 1.9,* 2.2§ | Data were also analysed separately for treatment groups: patients receiving infliximab (n = 44) or etanercept (n = 21). TC, LDL and the LDL:HDL ratio were increased versus baseline in the infliximab group only, while HDL was increased versus baseline in the etanercept group only. The authors conclude that the etanercept blockage of lymphotoxin-α may lead to less atherogenic lipid profiles. |
| Popa32 | As above | 3 mg/kg infliximab, weeks 0, 2, 6 and then every 8 weeks; DMARDs and oral corticosteroids were allowed (<10 mg/day)/12 months (n = 31 patients with RA) | TC (mmol/l): ↑;† 5.55,* Δ1.09 (mean values)HDL (mmol/l): ↔;† 1.37* (mean value)LDL (mmol/l): ↔;† 3.54* (mean value)TG (mmol/l): ↓;† 1.50,* Δ1.28 (mean values)TC/HDL: ↑;† 4.19,* Δ1.04 (mean values)LDL/HDL: ↔; 2.72* (mean value) | As aboveAfter 12 months of treatment, mean apo A and apo B values unchanged (1510* and 1024* mg/l, respectively). Also after 12 months, the cholesterol:HDL-cholesterol ratio was found to correlate positively with ESR. |
| Peters35 | As above | 3 mg/kg infliximab, weeks 0, 2, 6 and 14 weeks and, thereafter, every 8 weeks; MTX (15 mg/week) and prednisone were allowed (<10 mg/day)/48 weeks (n = 80 patients RA) | TC (mmol/l): ↔;† 4.79* (median value)HDL (mmol/l): ↔;† 1.46* (mean value)TG (mmol/l): ↔;† 1.26* (median value)TC/HDL: ↔;† 3.42* (median value) | As aboveFollowing 12 weeks treatment and compared with baseline, mean apo A-I levels were increased (1.58* vs 1.65§ g/l), while apo B levels were unchanged (0.93* g/l) and the mean apo B:apo A-I ratio was unchanged (0.62*). Inverse correlations were found between: disease activity, as determined by DAS28, and both HDL and TC levels, between CRP and both HDL and TC levels, and between disease activity and apo A-I. |
apo, apolipoprotein; BMI, body mass index; CRP, C-reactive protein; DAS28, disease activity index 28 joint score; DM, diabetes mellitus; DMARDs, disease-modifying antirheumatic drugs; ESR, erythrocyte sedimentation rate; HDL, high-density lipoprotein-cholesterol; LDL, low density lipoprotein-cholesterol; Lp(a) , lipoprotein(a); MTX, methotrexate; NSAIDs, non-steroidal anti-inflammatory drugs; RA, rheumatoid arthritis; TC, total cholesterol; TG, serum triglycerides; ↑, value increased; ↓, value decreased; ↔, value stable.
*Baseline value.
†Versus baseline.
‡Versus placebo.
§End-of-study-period value.
¶Change over time (study duration).