Background
Chronic plaque psoriasis is associated with overweight or
obesity. Anti\u2013tumour necrosis factor-
\u3b1
(anti-TNF-
\u3b1
) treatments are now
frequently used in psoriasis management. TNF-
\u3b1
is deeply involved in body
weight homeostasis, which may be affected by TNF-
\u3b1
\u2013targeted therapy.
Objective
To investigate whether anti-TNF-
\u3b1
treatments is associated with
changes in body weight in patients with chronic plaque psoriasis.
Methods
We performed a retrospective controlled analysis comparing the
variations in body weight and body mass index (BMI) in three closed cohorts
of psoriatic patients during a 6-month treatment with etanercept (
N
= 58),
infliximab (
N
= 40) or methotrexate (
N
= 43).
Results
We observed a body weight increment of 1.5
\ub1
2.7 kg (mean
\ub1
SD;
P
= 0.0002) and 2.5
\ub1
3.3 kg (
P =
0.004) in patients treated with etanercept and
infliximab, respectively. In contrast, a non-significant change (0.6
\ub1
1.4 kg;
P
= 0.4) was measured in patients treated with methotrexate. The BMI
increased with 0.5
\ub1
0.5 (
P =
0.01) and 0.8
\ub1
1 (
P =
0.003) points in patients
treated with etanercept and infliximab, respectively, whereas it did not change
(< 0.2
\ub1
0.5;
P
= 0.06) in patients treated with methotrexate. About one fourth
of patients experienced a 4- to 10-kg weight gain. Differences in body weight
variations among patients treated with anti-TNF-
\u3b1
therapies and methotrexate
were statistically significant (
P =
0.0005). We could not identify clinical parameters
predicting this phenomenon.
Conclusions
Patients with psoriasis treated with long-term anti-TNF-
\u3b1
therapies may manifest a body weight gain. This effect should be taken into
account in the global approach to patients with psoriasis

Cotena C

Girolomoni G

Gisondi P

Tessari G

Roubenoff R

Walsmith J

Visser M

Kirchgessner TG

Crossref

Anti–tumour necrosis factor-α therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort study

Background
Chronic plaque psoriasis is associated with overweight or
obesity. Anti–tumour necrosis factor-
α
(anti-TNF-
α
) treatments are now
frequently used in psoriasis management. TNF-
α
is deeply involved in body
weight homeostasis, which may be affected by TNF-
α
–targeted therapy.
Objective
To investigate whether anti-TNF-
α
treatments is associated with
changes in body weight in patients with chronic plaque psoriasis.
Methods
We performed a retrospective controlled analysis comparing the
variations in body weight and body mass index (BMI) in three closed cohorts
of psoriatic patients during a 6-month treatment with etanercept (
N
= 58),
infliximab (
N
= 40) or methotrexate (
N
= 43).
Results
We observed a body weight increment of 1.5
±
2.7 kg (mean
±
SD;
P
= 0.0002) and 2.5
±
3.3 kg (
P =
0.004) in patients treated with etanercept and
infliximab, respectively. In contrast, a non-significant change (0.6
±
1.4 kg;
P
= 0.4) was measured in patients treated with methotrexate. The BMI
increased with 0.5
±
0.5 (
P =
0.01) and 0.8
±
1 (
P =
0.003) points in patients
treated with etanercept and infliximab, respectively, whereas it did not change
(< 0.2
±
0.5;
P
= 0.06) in patients treated with methotrexate. About one fourth
of patients experienced a 4- to 10-kg weight gain. Differences in body weight
variations among patients treated with anti-TNF-
α
therapies and methotrexate
were statistically significant (
P =
0.0005). We could not identify clinical parameters
predicting this phenomenon.
Conclusions
Patients with psoriasis treated with long-term anti-TNF-
α
therapies may manifest a body weight gain. This effect should be taken into
account in the global approach to patients with psoriasis

GISONDI, Paolo

COTENA, CLAUDIA

TESSARI, Gianpaolo

GIROLOMONI, Giampiero

Catalogo dei prodotti della ricerca

 JEADV ISSN 1468-3083 © 2007 The Authors 341 JEADV  2008,  22 , 341–344 Journal compilation © 2007 European Academy of Dermatology and Venereology Blackwell Publishing LtdORIGINAL ARTICLE Anti–tumour necrosis factor- α  therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort study P Gisondi,* C Cotena, G Tessari, G Girolomoni Section of Dermatology, Department of Biomedical and Surgical Science, University of Verona, Verona, Italy Keywords anti-TNF-alpha therapy, body weight, chronic plaque psoriasis*Corresponding author, Section of Dermatology and Venereology, Department of Biomedical and Surgical Science, University of Verona, Piazzale A. Stefani 1, I-37126 Verona, Italy, tel. +39 045 8122547; fax +39 045 8300521; E-mail: paolo.gisondi@univr.itReceived: 16 April 2007, accepted 26 June 2007DOI: 10.1111/j.1468-3083.2007.02429.x Abstract Background Chronic plaque psoriasis is associated with overweight orobesity. Anti–tumour necrosis factor- α  (anti-TNF- α ) treatments are nowfrequently used in psoriasis management. TNF- α  is deeply involved in bodyweight homeostasis, which may be affected by TNF- α –targeted therapy. Objective To investigate whether anti-TNF- α  treatments is associated withchanges in body weight in patients with chronic plaque psoriasis. Methods We performed a retrospective controlled analysis comparing thevariations in body weight and body mass index (BMI) in three closed cohortsof psoriatic patients during a 6-month treatment with etanercept ( N  = 58),infliximab ( N  = 40) or methotrexate ( N  = 43). Results We observed a body weight increment of 1.5  ±  2.7 kg (mean  ±  SD; P  = 0.0002) and 2.5  ±  3.3 kg ( P =  0.004) in patients treated with etanercept andinfliximab, respectively. In contrast, a non-significant change (0.6  ±  1.4 kg; P  = 0.4) was measured in patients treated with methotrexate. The BMIincreased with 0.5  ±  0.5 ( P =  0.01) and 0.8  ±  1 ( P =  0.003) points in patientstreated with etanercept and infliximab, respectively, whereas it did not change(< 0.2  ±  0.5;  P  = 0.06) in patients treated with methotrexate. About one fourthof patients experienced a 4- to 10-kg weight gain. Differences in body weightvariations among patients treated with anti-TNF- α  therapies and methotrexatewere statistically significant ( P =  0.0005). We could not identify clinical para-meters predicting this phenomenon. Conclusions Patients with psoriasis treated with long-term anti-TNF- α therapies may manifest a body weight gain. This effect should be taken intoaccount in the global approach to patients with psoriasis. Introduction Chronic plaque psoriasis is associated with obesity in12.9% to 34% of cases. 1–4  Although the directionality ofthis positive correlation is still unclear, two studies suggestthat overweight and obesity appear after the onset ofpsoriasis. 1,5  In contrast, two other studies found a highprevalence of obesity in patients with recent onsetpsoriasis, suggesting that obesity precedes and mayrepresent a risk factor for psoriasis. 2,6  Obesity is a strongrisk factor for hypertension and type 2 diabetes, and all ofthese are important cardiovascular risk factors. Indeed, ithas been documented that there is an increased mortal-ity from cardiovascular diseases in patients with severepsoriasis, and psoriasis may confer an independent risk ofmyocardial infarction especially in young patients. 7,8 Anti–tumour necrosis factor- α  (anti-TNF- α ) treatments arenow frequently used in psoriasis management. TNF- α  isdeeply involved in body weight homeostasis, which maybe affected by TNF- α –targeted therapy. Recently, body Anti-TNF-alpha drugs and body weight in patients with psoriasis Gisondi  et al. 342 © 2007 The Authors JEADV  2008,  22 , 341–344 Journal compilation © 2007 European Academy of Dermatology and Venereology weight gain has been reported both in patients withspondyloarthropathy 9  and patients with Crohn’s disease 10 treated with anti-TNF- α  inhibitors. We conducted aretrospective cohort study aimed to see whether anti-TNF- α  treatments are associated with changes in bodyweight in patients with psoriasis. Materials and methods Study population One hundred and forty-one psoriatic patients consecutivelyadmitted to the outpatients clinics of the UniversityHospital of Verona were involved. The source populationof the study was people living in city of Verona or in theneighbourhood. Patients were affected by chronic plaquepsoriasis diagnosed according to clinical criteria. Patientswith psoriatic arthritis diagnosed according to theCASPAR criteria were excluded. 11  All subjects were visitedby a dermatologist who registered demographical, bio-metrical and the other relevant data on a case reportform. Visits were scheduled at baseline and every 2 monthsfor patients treated with methotrexate and etanercept,whereas visits were scheduled at each infusion forpatients receiving infliximab. Relevant data collectedincluded age, gender, weight, height, body mass index(BMI), age of psoriasis onset, type and severity of psoriasisand concomitant medications. BMI was calculated asweight (kg)/height (cm 2 ). Severity of psoriasis was assessedaccording to the Psoriasis Area and Severity Index(PASI) and body surface area (BSA). Venous samples weretaken at baseline visit and every 2 months after thesubjects had fastened overnight (at least 8 h). Patientswere treated with methotrexate, etanercept or infliximab,respectively. The indications for anti-TNF- α  treatmentswere chronic plaque psoriasis with a PASI score and aBSA% involvement of more than 10 and resistance orintolerance to methotrexate, cyclosporin, acitretin or photo-therapy. Etanercept and infliximab were randomly assignedto patients resistant or intolerant to methotrexate, whichwas used as the first choice drug. All patients who receivedetanercept or infliximab were biological therapy naïve.Doses of systemic drugs used were as follows: methotrexatewas given 15 mg once weekly by intramuscular injection;etanercept 25 mg twice weekly by subcutaneous injections;and infliximab 5 mg/kg at week 0, 2, 6 and then every8 weeks by intravenous infusion. Statistical analysis Analysis was made using the STATA (version 6.0 Stata-Corp LP, College Station, TX, USA) and Graphpad (version4.0 GraphPad Software, El Camino Real, San Diego, CA, USA)software packages. Standard descriptive statistics, such asmean and standard deviation, were computed. Differencesin body weight, BMI, PASI score, plasma glucose, totalcholesterol and triglycerides within groups were comparedusing Wilcoxon’s signed rank sum test. Differencesbetween groups were compared using  ANOVA  test correctedusing the Bonferroni formula. Associations between bodyweight increment and categorical variables (age andgender) were tested by Fisher exact test, whereas  t -testwas used for continuous variables (BMI, body weight,PASI score and serum lipids). All  P -values are two sided,and  P  < 0.05 was considered statistically significant. Results Forty-three patients treated with methotrexate, 58patients with etanercept and 40 patients with infliximabwere included in the study (Table 1). At enrolment, nosignificant differences in age, sex, body weight and BMIwere present among the three groups of patients. Psoriasisduration was also similar in the three groups, whereaspatients treated with methotrexate had a lower PASIscore. At 6 months, we observed a mean body weightincrement of 1.5  ±  2.7 kg ( ±  SD;  P  = 0.0002) and 2.5  ±  3.3 kg( P =  0.004) in patients treated with etanercept and in-fliximab, respectively. In contrast, a non-significant change(–0.6  ±  1.4 kg;  P  = 0.4) was measured in patients treatedwith methotrexate. In particular, in the etanercept cohort,6 patients (10.3%) lose weight; 15 patients (25.8%)did not show body weight variation; 24 patients (41.3%)increased weight by 1 to 3 kg; and 13 patients (22.4%)increased weight by 4 to 10 kg. In the cohort of infliximab,3 patients (7.5%) lose weight, 7 (17.5%) did not showbody weight change; 19 patients (47.5%) increasedweight by 1 to 3 kg; and 11 patients (27.5%) increasedweight by 4 to 10 kg. In the methotrexate cohort, 8patienta (18.6%) lose weight; 32 patients (74.4%) didnot show body weight variation; and 3 patients (6.9%)increased weight by 1 to 3 kg. The BMI increased with0.5  ±  0.5 (mean  ±  SD;  P  = 0.01) and 0.8  ±  1 ( P =  0.003)points in patients treated with etanercept and infliximab,respectively, whereas it did not change (–0.2  ±  0.5;  P  =0.06) in patients treated with methotrexate. Differences inbody weight variations among patients treated with anti-TNF- α  therapies and methotrexate were statistically signific-ant ( P =  0.0005). The relative risk of gaining  ≥  5 kg of bodyweight among patients exposed to anti-TNF- α  treatmentswas 4.3 times higher than in patients exposed to metho-trexate. There were no differences in body weight meanincrement according to age group (> 50 or < 50 years old),gender, BMI classes and psoriasis severity (PASI score > 10or < 10) at enrolment. After 6 months of treatment, meanPASI score was decreased by 47.1% ( P =  0.0002), 74.5% Gisondi  et al. Anti-TNF-alpha drugs and body weight in patients with psoriasis © 2007 The Authors 343 JEADV  2008,  22 , 341–344 Journal compilation © 2007 European Academy of Dermatology and Venereology ( P =  0.0001) and 88.8% ( P =  0.0001) in patients treatedwith methotrexate, etanercept and infliximab, respectively.No significant changes in fasting plasma glucose, totalcholesterol and triglycerides mean levels were observed inany of the three groups as well as no severe adverseevents. Discussion These data show that patients with psoriasis receiv-ing anti-TNF- α  therapy, but not those treated withmethotrexate, may manifest a significant body weightgain after 6 months of treatment. A relevant increase(4–10 kg) in body weight was observed in about 25% ofpatients treated with etanercept or infliximab. We couldnot identify clinical parameters predicting this phenomenon.No patients referred modifications in eating behaviourand physical activity and/or increment of appetite oranorexia. We did not study body composition by bio-impedance, whereas Briot  et al . reported an increase inbody weight, bone mineral density and in lean mass, butnot in fat mass, in parallel with an increase in insulin-likegrowth factor-1 in patients with spondyloarthropathies(including psoriatic arthritis) receiving a 1-year anti-TNF- α  treatment. 9  In contrast, no studies have reportedbody weight gain in patients with rheumatoid arthritisafter anti-TNF- α  therapy. Therefore, it is possible that thedifferent type of inflammation/immune response or thegenetic background (usually patients with rheumatoidarthritis are lean) is important in determining whetheranti-TNF- α  can favour weight gain. Our study has severallimitations, including the possible selection of the moresevere psoriatic patients in the anti-TNF- α –treated group.Although baseline PASI scores were not significantlydifferent in the three groups, etanercept and infliximabwere randomly assigned to patients resistant or intolerantto methotrexate or other traditional systemic therapies,which were used as the first-line therapy.The reason for the increased weight among patientstreated with anti-TNF- α  agents is not known. TNF- α /cachectin  α  is deeply involved in body weight homeostasisby favouring muscle cell catabolism both in physiologicaland pathological conditions. 12–14  Anti-TNF- α  treatmentmay have and indirect positive effect on lean massthroughout the general health improvement of patients,leading to increase of appetite. Indeed, TNF- α  caninfluence appetite through modulation of leptin releasefrom adipocytes. 15  Franchimont  et al . observed that a4-week infliximab treatment induced a body weight andan increase in leptin serum levels in patients with Crohn’sdisease. 10  We did not observe differences in plasma trigly-cerides and cholesterol levels following any treatments,although significant elevation in plasma lipids have beenreported in some patients with rheumatoid arthritis orpsoriasis treated with TNF- α  inhibitors. 16,17  On the otherhand, recent reports suggest TNF- α  inhibitors can improveTable 1 Study population. Descriptive characteristic of the three groups of patientsMTXΔwithin group* EtanerceptΔwithin group* InﬂiximabΔwithin group*Δbetween groups†Number 43 58 40Sex, F/M 17/26 19/39 12/28 0.5Age (y), mean ± SD 53.1 ± 12.7 50.2 ± 11.1 46.8 ± 11.2 0.7Psoriasis duration (y), mean ± SD 18.6 ± 12  22 ± 12.9 17.5 ± 13.4 0.2Body weight at enrolment, mean ± SD 81.0 ± 12.6 80.1 ± 16.2 79.2 ± 15.2 0.9Body weight at month 6, mean ± SD 79.2 ± 13.9 0.4 81.7 ± 16.4 0.0002 81.8 ± 16.9 0.004 0.6BMI at enrolment, mean ± SD 27.4 ± 3.6 27.6 ± 5 26.5 ± 3.5 0.6BMI at month 6, mean ± SD 27.3 ± 3.8 0.06 28.1 ± 5 0.01 27.3 ± 3.8 0.003 0.7PASI at enrolment, mean ± SD 8.2 ± 3.1 18.8 ± 7.4 17.7 ± 7.3 0.0001‡; 0.6§PASI at month 6, mean ± SD 4.3 ± 6 0.0002 4.8 ± 4.7 0.0001 2.1 ± 3.2 0.0001PASI mean improvement percentage 47.6 74.5 88.8 0.0004‡; 0.02§Total cholesterol level at enrolment, mean ± SD  234 ± 16.8  233 ± 15.1 235.3 ± 14.2 0.8‡; 0.7§Total cholesterol level at month 6, mean ± SD  236 ± 18.1 0.4  235 ± 17.3 0.5  237 ± 16.9 0.6Triglycerides levels at enrolment, mean ± SD  170 ± 17.8  168 ± 18.3  172 ± 18.1Triglycerides levels at month 6, mean ± SD  175 ± 18.9 0.2  167 ± 19.4 0.7  170 ± 16.2 0.09*Differences within groups were compared using Wilcoxon’s signed rank sum test;†Differences between groups were compared using ANOVA test corrected using Bonferroni formula;‡Methotrexate vs. etanercept or inﬂiximab;§Etanercept vs. inﬂiximab.MTX, methotrexate.Anti-TNF-alpha drugs and body weight in patients with psoriasis Gisondi et al.344 © 2007 The AuthorsJEADV 2008, 22, 341–344 Journal compilation © 2007 European Academy of Dermatology and Venereologymetabolic parameters and reduce cardiovascular riskfactors. In particular, TNF-α blockade has been shown toimprove insulin resistance, reduce serum levels of C-reactive protein and carotid intima-media thickness inpatients with rheumatoid arthritis.18,19The potential effect of anti-TNF-α treatments on bodyweight should be taken into account in the long-termtheir use in overweight and obese psoriatic patients.References1 Herron MD, Hinckley M, Hoffman MS et al. Impact of obesity and smoking on psoriasis presentation and management. Arch Dermatol 2005; 141: 1527–1534.2 Naldi L, Chatenoud L, Linder D et al. Cigarette smoking, body mass index, and stressful life events as risk factors for psoriasis: results from an Italian case-control study. J Invest Dermatol 2005; 125: 61–67.3 McGowan JW, Pearce DJ, Chen J, Richmond D, Balkrishnan R, Feldman SR. The skinny on psoriasis and obesity. Arch Dermatol 2005; 141: 1601–1602.4 Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB, Gelfand JM. Prevalence of cardiovascular risk factors in patients with psoriasis. J Am Acad Dermatol 2006; 55: 829–835.5 Mallbris L, Granath F, Hamsten A, Stahle M. Psoriasis is associated with lipid abnormalities at the onset of skin disease. J Am Acad Dermatol 2006; 54: 614–621.6 Mallbris L, Larsson P, Bergqvist S, Vingard E, Granath F, Stahle M. Psoriasis phenotype at disease onset: clinical characterization of 400 adult cases. J Invest Dermatol 2005; 124: 499–504.7 Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA 2006; 296: 1735–1741.8 Ludwig RJ, Herzog C, Rostock A et al. Psoriasis: a possible risk factor for development of coronary artery calcification. Br J Dermatol 2007; 156: 271–276.9 Briot K, Garnero P, Le Henanff A, Dougados M, Roux C. Body weight, body composition, and bone turnover changes in patients with spondyloarthropathy receiving anti-tumour necrosis factor alpha treatment. Ann Rheum Dis 2005; 64: 1137–1140.10 Franchimont D, Roland S, Gustot T et al. Impact of infliximab on serum leptin levels in patients with Crohn’s disease. J Clin Endocrinol Metab 2005; 90: 3510–3516.11 Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H; CASPAR Study Group. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 2006; 54: 2665–2673.12 Roubenoff R, Roubenoff RA, Cannon JG et al. Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation. J Clin Invest 1994; 93: 2379–2386.13 Walsmith J, Abad L, Kehayias J, Roubenoff R. Tumor necrosis factor-alpha production is associated with less body cell mass in women with rheumatoid arthritis. J Rheumatol 2004; 31: 23–29.14 Visser M, Pahor M, Taaffe DR et al. Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol a Biol Sci Med Sci 2002; 57: 326–332.15 Kirchgessner TG, Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS. Tumor necrosis factor-alpha contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes. J Clin Invest 1997; 100: 2777–2782.16 Sattar N, Crompton P, Cherry L, Kane D, Lowe G, McInnes IB. Effects of tumor necrosis factor blockade on cardiovascular risk factors in psoriatic arthritis: a double-blind, placebo-controlled study. Arthritis Rheum 2007; 56: 831–839.17 Seriolo B, Paolino S, Sulli A, Fasciolo D, Cutolo M. Effects of anti-TNF-alpha treatment on lipid profile in patients with active rheumatoid arthritis. Ann N Y Acad Sci 2006; 1069: 414–419.18 Porto FD, Lagana B, Lai S et al. Response to anti-tumour necrosis factor alpha blockade is associated with reduction of carotid intima-media thickness in patients with active rheumatoid arthritis. Rheumatology (Oxford) 2007.19 Bernstein LE, Berry J, Kim S, Canavan B, Grinspoon SK. Effects of etanercept in patients with the metabolic syndrome. Arch Intern Med 2006; 166: 902–908.

Anti-tumour necrosis factor-alpha therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort study.

https://iris.univr.it/bitstream/11562/604363/1/2008_Gisondi-P._Girolomoni-G._J.-Eur.-Acad.-Dermatol.-Venereol._Anti-tumour-necrosis-factor--therapy-increases-body-weight-in-patients-with-chronic-plaque-psoriasis-A-retrospective-cohort-study_Jour.pdf

Anti-tumour necrosis factor-alpha therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort study.

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