CASE REPORT

Efficacy and safety of adalimumab in a patient with ankylosingspondylitis on peritoneal dialysis

Senol Kobak

Received: 22 December 2009 / Accepted: 12 March 2010 / Published online: 26 March 2010

� Springer-Verlag 2010

Abstract The most commonly used treatments in patients

with ankylosing spondylitis include nonsteroidal anti-

inflammatory and disease modifying anti-rheumatic drugs

(DMARDs), but most of these have nephrotoxic effects. In

patients who undergo chronic hemodialysis, DMARDs are

not widely preferred due to the chance of increased adverse

effect incidence and the risk on patient survival, in addition

to already present immunosuppression. The efficacy and

safety of anti-TNF alpha drugs for the treatment of renal

dysfunction that develops associated to secondary amy-

loidosis in inflammatory rheumatic diseases have been

reported in various studies. In this report, the efficacy and

safety of adalimumab was shown in patients with active

ankylosing spondylitis who undergo peritoneal dialysis

because of chronic renal failure.

Keywords Ankylosing spondylitis � Peritoneal dialysis �Adalimumab

Introduction

Ankylosing spondylitis (AS) is a chronic inflammatory

disease that courses with involvement of sacroiliac joint,

axial, and peripheral joints. The most important compli-

cations of AS include secondary amyloidosis and associ-

ated end-stage renal failure [1]. Treatment of AS includes

mainly non-steroidal anti-inflammatory drugs (NSAIDs) in

addition to disease modifying anti-rheumatic drugs

(DMARDs). The efficacy and safety of anti-TNF-alpha

drugs, which opened a new era in AS treatment, have been

recently demonstrated. There is a limited number of

DMARDs that can be used in the treatment of AS patients

with chronic renal failure [2]. Increased side effect inci-

dence, nephrotoxicity/hepatotoxicity, and occasionally

serious bone marrow suppression have been reported. In

this case, anti-TNF-alpha drugs represent the most decent

drugs and should be the most commonly preferred ones for

the treatment of patients with active AS who undergo

dialysis because of chronic renal failure. The literature on

this subject is limited and includes contradictory informa-

tion. Pharmacokinetics of etanercept has been investigated

in patients undergoing hemodialysis due to end-stage renal

failure [3]. The results were similar with the patients with

normal kidney functions, and no side effect has been noted

during six months of follow-up. The efficacy and safety of

another TNF-alpha antagonist, adalimumab, have been

established in patients with active AS. However, literature

contains no information regarding the pharmacokinetics of

adalimumab in patients undergoing dialysis due to renal

failure. In this case report, the efficacy and safety of ada-

limumab have been demonstrated in a 65-year-old male

patient with active AS who undergone peritoneal dialysis

due to renal failure.

Case presentation

A 65-year-old male patient had been followed up with

diagnosis of ankylosing spondylitis for 15 years. The

patient was diagnosed with chronic renal failure 6 years

ago, and peritoneal dialysis was initiated. The patient had

S. Kobak (&)

Department of Rheumatology, Manisa Hospital, Manisa, Turkey

e-mail: senolkobak@yahoo.com

S. Kobak

Manisa Devlet Hastanesi, Manisa, Turkey

123

Rheumatol Int (2012) 32:1785–1787

DOI 10.1007/s00296-010-1457-7

significant increase in the complaints of inflammatory back

pain and morning stiffness and was referred to our clinics.

Physical examination revealed ankylosing spondylitis

posture, while bilateral FABERE and FADIR were posi-

tive. Following measurements were noted: jaw-sternum

distance 4 cm, chest expansion 2 cm, occiput-wall distance

12 cm, Schober test 2 cm. BASDAI was 8.9 cm (0–

10 cm), and BASFI was 8.2 cm (0–10 cm). Laboratory

analysis revealed chronic disease anemia, urea: 134 mg/dl

(normal 15–50 mg/dl), creatinine: 5.6 mg/dl (normal 0.6–

1.3 mg/dl), protein: 5.1 g/dl (normal: 6.4–8.3 g/dl), serum

albumin: 1.9 g/dl (normal: 3.5–5.0 g/dl). Among acute-

phase responses; erythrocyte sedimentation rate (ESR) was

125 mm/h (normal B 30 mm/h), C-reactive protein (CRP)

was 101 mg/l (normal 0–5 mg/l). In the subcutaneous

adipose tissue and rectum biopsies performed for the

assessment of secondary amyloidosis, amyloid was detec-

ted by Congo-Red dye. The patient had active disease

despite treatment with low-dose corticosteroid (4 mg/day),

salazopyrine (SLZ) 2 g/day, and NSAIDs. The patient had

previously experienced severe pancytopenia due to meth-

otrexate (MTX) use and this treatment was ceased. In light

of this information, the patient was prescribed adalimumab.

No pathology was detected in the lung graphy and

tomography. PPD test result was 9 mm, and treatment was

initiated with isoniazid 300 mg/day. After obtaining the

patients written consent, treatment was initiated with ada-

limumab 40 mg administered subcutaneously every other

week. Improvements were noted in clinical and laboratory

findings of the patient at the follow-up visit performed

4 weeks after the initial drug administration. At the 12th

week of treatment, significant remission was observed in

the complaints of the patient and the examinations revealed

improvement. Occiput-wall distance was measured as

8 cm, chest expansion was 4 cm, jaw-sternum distance was

2 cm, and Schrober test result was 4 cm. BASDAI and

BASFI scores were within normal range. At the 3rd month

of treatment, the patient’s overall health status was good,

the complaints of inflammatory back pain and morning

stiffness were eliminated, and significant improvement was

noted in the parameters that were being followed up

(Table 1). No side affect has been noted in the patient

during treatment.

Discussion

In this case report, efficacy and safety of adalimumab were

demonstrated in a patient with active AS who was under-

going peritoneal dialysis. Marked clinical and laboratory

regression were noted in the patient. AS-associated com-

plaints were eliminated, duration of morning stiffness and

movement limitation was reduced to less than 10 min, and

disease activation criteria achieved normal levels. Signifi-

cant regression was noted in acute-phase responses (ESR

and CRP), and the levels of serum albumin and hematocrit

increased (Table 1). There was no side effect in the patient

during 12 weeks of treatment. As far as we know, no

similar case has been reported in the literature before.

The literature includes no information on the pharma-

cokinetics of adalimumab in patients undergoing chronic

dialysis. Since adalimumab is hydrolyzed in lysosomes as

other anti-TNF-alpha antagonists (etanercept, infliximab), it

has no effect on renal functions. For this reason, it can be

safely administered for short periods to the patients under-

going dialysis. It should be kept in mind that some level of

malfunctioning can be noted in defense mechanisms of

immune systems of the patients with renal failure who

undergo dialysis. Reduced kidney clearance of various

toxins and administration of immunosuppressive drugs may

lead to life-threatening serious infections. For this reason,

this possibility should be considered during anti-TNF-alpha

treatment. Literature contains limited information regarding

the use of anti-TNF-alpha drugs in patients with renal

failure (Table 2). Don et al. [3] have administered etaner-

cept to six patients undergoing hemodialysis (HD). They

assessed pre- and post-dialysis serum etanercept concen-

trations and did not observe any change. Compared to

patients with normal kidney functions, pharmacokinetics of

etanercept in patients undergoing HD was similar. No side

effect was noted during 6 months of treatment. Sugioka

et al. [4] have administered etanercept to a patient with RA

who was undergoing hemodialysis. At the end of 12-week

treatment, significant regression was observed in the patient

without any side effect. Cassano et al. [5] administered

etanercept to a patient with cyclosporine-resistant psoriasis

and hepatitis C virus who was undergoing HD due to

polycystic kidney disease. Significant regression was noted

Table 1 Clinical and laboratory follow-up of patient with AS on peritoneal dialysis during adalimumab treatment

Follow-up BASDAI (0–10 cm) BASFI (0–10 cm) ESR (mm/h) CRP (mg/dl) Hematocrit (%) Albumin (g/dl)

Baseline 8.9 8.2 125 101 29 1.9

4 week 5.4 6.1 73 24 31 2.5

12 week 4.2 4.9 38 6.6 35 3.2

1786 Rheumatol Int (2012) 32:1785–1787

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in the PASI scores of the patient while there was no increase

in liver functions or HCV viral load. Hammoudeh et al. [6]

have demonstrated the efficacy and safety of infliximab in a

patient with active RA who was undergoing hemodialysis.

Yee et al. administered infliximab to a patient with com-

plicated sarcoidosis who was undergoing hemodialysis.

Although there was clinical improvement, the treatment

was stopped because of hypercoagulation in the patient [7].

Ortiz-Santamaria et al. administered infliximab to six

patients with secondary amyloidosis (five associated with

RA and one associated with AS). Two of these patients were

undergoing hemodialysis, and treatment was stopped in one

due to development of pancytopenia while no side effect

was observed in the other [8]. Singh et al. [9] reported a

patient with RA who failed to respond to treatment with

several DMARDs and responded well to infliximab.

Pharmacokinetics of anti-TNF-alpha drugs in patients

undergoing dialysis is not exactly known. It is possible to

suggest that they have fewer side effects compared to other

DMARDs. NSAIDs represent the first step of AS treatment

but they can be used for very short durations due to

increased risk of hemorrhage. Although MTX is an effec-

tive immunosuppressive drug especially for peripheral

joint involvement, it is eliminated by kidney. Its use is

limited since it may cause life-threatening pancytopenia in

some patients [10, 11]. Salazosulfapyridine is also excreted

renally, indicating that drug clearance is influenced by

renal function. However, dialysis appears to affect clear-

ance in HD, and the drug may be used if the dose is ade-

quately reduced [12]. Low-dose steroid treatment results in

development of hypertension associated with fluid accu-

mulation and volume overload. Use of anti-TNF-alpha

drugs in the treatment of patients with inflammatory

rheumatoid disease who suffer from chronic renal failure

might be considered. These treatments should be admin-

istered under close monitoring and follow-up, after esti-

mating benefit-risk ratio in each patient and taking the

infection risk and immunosuppression status of the patients

into consideration. Controlled clinical trials including large

patient populations are required.

Conflict of interest statement None.

References

1. Hazenberg BP, van Rijswijk MH (1994) Clinical and therapeutic

aspects of AA amyloidosis. Baillieres Clin Rheumatol 8:661–690

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In: Brenner BM (ed) Brenner and Rector’s the kidney, vol 2, 7th

edn. Saunders, Philadelphia, pp 2850–2870

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etanercept in patients with end-stage renal disease on haemodi-

alysis. J Pharm Pharmacol 57:1407–1413

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with rheumatoid arthritis on hemodialysis. Mod Rheumatol

18:293–295

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J Rheumatol 29:636–637

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in a patient undergoing hemodialysis. J Rheumatol 26:1424–1425

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(2001) Severe methotrexate intoxication in a hemodialysis patient

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Table 2 Anti-TNF-alpha drugs in patients with end-stage renal disease on dialysis- summary of all important case series in literature

Sugioka et al.

[4]

Cassano et al.

[5]

Singh et al.

[9]

Hammoudeh

et al. [6]

Yee et al.

[7]

Ortiz-Santamaria

et al. [8]

Present

study

Anti-TNF-alpha drug Etanercept Etanercept Infliximab Infliximab _Infliximab _Infliximab Adalimumab

Hemodialysis/Periton

dialysis

HD HD HD HD HD HD PD

Efficacy ? ? ? ? ? ? ?

Side effect - - - Transient itching Hypercoagulation Pansitopenia -

Disease RA PsA ? HCV RA RA Sarcoidosis RA AS

Follow-up period 12 weeks 24 weeks 2 years 6 months 12 weeks

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