Frequency and duration of clinical remission in patients with peripheral psoriatic arthritis requiring second-line drugs

Transcription

1 Rheumatology 2008;47: Advance Access publication 9 April 2008 doi: /rheumatology/ken059 Frequency and duration of clinical remission in patients with peripheral psoriatic arthritis requiring second-line drugs F. Cantini 1, L. Niccoli 1, C. Nannini 1, E. Cassara` 1, P. Pasquetti 1, I. Olivieri 2 and C. Salvarani 3 Objective. To evaluate the frequency and duration of clinical remission in patients with PsA. Methods. All consecutive new outpatients with peripheral PsA requiring second-line drugs and RA observed between January 2000 and December 2005 were included in a prospective, case-control study. Primary end point was to assess the frequency of remission in peripheral PsA compared with RA. Secondary end points were to compare the duration of clinical remission during treatment and after therapy interruption, ACR 20, 50, 70 response rates and to detect any remission predictor at diagnosis. Treatment regimen was standardized in both groups. From January 2003 to December 2005, therapy was suspended in PsA patients and controls if achieving remission. Results. One or more episodes of remission occurred in 57/236 (24.1%) PsA patients and in 20/268 (7.5%) controls (P < 0.001). The mean duration of remission was of months in PsA patients and in controls (P > 0.001). Remission episodes were more frequent in PsA patients treated with anti-tnf compared with those receiving traditional DMARDs (P > 0.001), with no differences regarding the duration. After therapy interruption, the remission duration was months in PsA and in RA (P < 0.001). No remission predictor at diagnosis resulted by multivariate analysis. Conclusion. Remission is possible in up to 24% of patients with peripheral PsA. It is significantly more frequent, but not longer, in patients receiving anti-tnf drugs compared with those treated with traditional DMARDs. Patients remain in remission for a long period after therapy interruption, thus suggesting an intermittent therapeutic strategy. KEY WORDS: PsA, Clinical remission, Remission criteria, DMARDs, Anti-TNF drugs, MTX, RA. Introduction PsA has been defined as an inflammatory arthritis associated with psoriasis, usually seronegative for RF [1]. At onset, at least five clinical patterns of PsA have been described, with different course and severity [1]. However, in around half of the cases the clinical characteristics at presentation tend to change over time [2 4], and during the course of the disease patients usually present three main patterns of articular involvement: peripheral oligopolyarthritis without axial involvement, isolated psoriatic spondylitis and concurrent involvement of peripheral and axial articular structures [5]. PsA has long been considered a benign disease, but differently from previously thought, several follow-up studies have demonstrated an aggressive course with development of articular erosions and deformities in around 50% of the cases [6, 7]. Several predictors of disease severity at diagnosis have been identified: involvement of five or more joints at onset, elevated ESR, late onset, HLA-B27 positivity for PsA spondylitis and expression of gene polymorphism alleles TNF--308 and TNF--252 represent markers of a more aggressive course [8 12]. PsA management is strictly related to the severity of the disease. Mild monoarticular or oligoarticular peripheral variants of PsA are usually treated with local injection therapy and NSAIDs, eventually associated with short-term, low-dose corticosteroids (CS) [13]. Non-responders and patients with polyarthritis at onset require a more aggressive therapy with second-line drugs, including traditional DMARDs, LEF and anti-tnf- agents [13]. MTX, SSZ and CsA, either alone or in combination, are the most widely used traditional DMARDs [14]. Due to its 1 2nd Division of Medicine, Rheumatology Unit, Hospital of Prato, 2 Rheumatology Department of Lucania, S. Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera and 3 Division of Rheumatology, Arcispedale S. Maria Nuova, Reggio Emilia, Italy. Submitted 15 November 2007; revised version accepted 24 January Correspondence to: F. Cantini, 2nd Department of Medicine-Rheumatology Unit, Hospital of Prato, Piazza Ospedale, , Prato, Italy. fcantini@usl4.toscana.it; cantini.fabrizio@virgilio.it good risk benefit ratio, MTX is considered the drug of choice in the treatment of peripheral PsA [15]. Before the introduction of biologics, switching to another DMARD or combined DMARDs therapy were employed in PsA patients resistant to MTX. Although not easily valuable due to the different outcome measures, studies on the efficacy of traditional DMARDs in the treatment of PsA show a significant efficacy compared with placebo, with a response ratio ranging from 20% to 50% of the patients [16]. Better results have been obtained with LEF and anti- TNF- drugs, with a response rate of 50 70% [17 19]. Similarly to RA, response to therapy in PsA is usually measured in terms of percentage improvement with respect to baseline, but rarely patients have been evaluated for clinical remission [20]. Moreover, differently from RA [21], remission criteria for PsA have not yet been defined. However, in keeping with other authors [20, 22], over 15 yrs of activity of our rheumatological centre, we noted PsA patients who experienced prolonged remission both during treatment and after therapy interruption. We designed a prospective, follow-up, case control study to evaluate the frequency of clinical remission in patients with peripheral PsA, and the duration of remission episodes both during treatment and over the off-therapy follow-up period. Patients and methods Study design A prospective, follow-up, case control study design was adapted. Case patients All consecutive new outpatients with peripheral PsA requiring second-line drugs observed between January 2000 and December 2005 at the Rheumatology Unit of the Hospital of Prato, Italy. Controls All consecutive new outpatients meeting the 1987 revised criteria of the ACR (formerly, the American Rheumatism Association) for the classification of RA [23] observed over the same period. 872 ß The Author Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please journals.permissions@oxfordjournals.org

2 Remission in PsA 873 Primary end-point To evaluate the frequency of clinical remission in patients with peripheral PsA, as expressed by the percentage of patients fulfilling the modified (see below) ACR remission criteria [21], compared with that observed in patients with RA. Secondary end-points To compare in case-patients and controls the duration of clinical remission during treatment and after therapy interruption, to evaluate the ACR 20, 50, 70 response rates [24] at the end of follow-up, and to evaluate the correlation between initial clinical and laboratory variables and the frequency of remissions. Definitions PsA: inflammatory arthritis associated with psoriasis, usually seronegative for RF. Peripheral PsA: presence of at least one swollen and tender joint, without clinical evidence of axial involvement. PsA spondylitis: patients meeting the modified New York criteria for AS [25]. Monoarthritis: tenderness and swelling of one joint. Oligoarthritis: tenderness and swelling of four or fewer peripheral joints. Polyarthritis: tenderness and swelling of five or more peripheral joints. Dactylitis: diffuse tenderness and swelling of the entire digit with sausage aspect. Enthesitis: tenderness and swelling at sites of tendon, ligament and joint capsule insertion into bone. Enthesitis was assessed according to the Mander s enthesis index [26]. Inflammatory spinal pain: patients were defined as presenting inflammatory spinal pain if they met the Calin s criteria for this clinical feature [27]. Non-responders: patients and controls failing to achieve or maintain an ACR 20% clinical response. Exclusion criteria: patients with inflammatory spinal pain [27] at presentation or during the disease course, or meeting the modified New York criteria for AS [25], and those with contraindications to the use of traditional DMARDs and anti- TNF- drugs were excluded from the study. Disease remission: basically, we used the ACR criteria for RA [21] to define the clinical remission in PsA patients. As summarized in Table 1, these criteria include fatigue and pain 10 (measured by visual-analogue scale mm), articular morning stiffness 15 min, absence of tender and swollen joints, ESR 20 mm/h in males and 30 mm/h in females, and patients should satisfy five out of the six items. Considering the different clinical features of peripheral PsA, TABLE 1. Remission criteria for peripheral PsA a. Patients were considered in remission if all items were fulfilled Item Value Fatigue (VAS mm) < 10 Pain (VAS mm) < 10 Articular morning stiffness (min) 15 Tender joint count 0 Swollen joint count 0 Normal ESR (mm/h) Women 30 Men 20 Normal CRP (mg/dl) 0.5 Dactylitis (/Present) b Enthesitis/tenosynovitis (absent/present) Inflammatory spinal pain (absent/present) Extra-articular features (absent/present) a Adapted from ACR remission criteria for RA [21]. b Enthesitis was assessed according to Mander s enthesitis index [26]. we adapted them by adding the following items: enthesitis, dactylitis and extra-articular features [6], with the exception of psoriasis. Moreover, as CRP is considered a more sensitive indicator of disease activity compared with ESR in all inflammatory arthritis [28, 29], normal CRP value (<0.5 mg/dl, nephelometric method) was added as a criterion. Controls with RA were evaluated by using the ACR remission criteria [21]. Patients of both groups treated with traditional DMARDs or anti-tnf- drugs were considered in clinical remission if satisfying the previously described criteria and without taking any additional drug including NSAIDs and CS for at least two consecutive visits. Relapse: patients and controls were considered as relapsing in the case of recurring of any articular or extra-articular clinical manifestation, independently on the acute-phase reactants values. Treatment regimen PsA patients presenting with mono-oligoarthritis were initially treated with NSAIDs, and local infiltrative therapy when indicated. Short-term, low-dose CS were added in resistant patients with oligoarthritis. Non-responders were given MTX at the dose of mg/week added to NSAIDs for at least 6 months. Before the year 2003, in the case of treatment failure, CsA at the dose of 3 5 mg/kg/day was added to MTX. Switching to CsA was done in case of intolerance to MTX, and CS were permitted in case of resistance to therapy. PsA patients presenting with polyarthritis were scheduled to start MTX and NSAIDs at diagnosis. Non-responders were treated with the same schedule described earlier. Anti-TNF- agents infliximab and etanercept use for PsA was approved by the Italian Ministry of Health since the beginning of the year Consequently, after this date, patients who were non-responders to previous therapy with MTX alone or to previous combined therapy with MTX and CsA were switched to one of the two TNF- blockers associated with MTX, after an amendment to the protocol was approved by the local ethical committee. In case of MTX intolerance, anti-tnf was given alone. During the last 3 yrs, in PsA patients and controls achieving and maintaining clinical remission for at least 4 months the treatment was interrupted and patients were followed up over time. In case of relapse, they were given the same treatment regimen received before the interruption. Before the year 2003, patients relapsing after remission were treated adding CS to previous therapy. RA patients were given MTX at the dose of mg/week associated with NSAIDs and low-dose CS. As TNF- blockers were approved in Italy for use in RA in the year 2000, infliximab, etanercept and more recently adalimumab were added in RA patient non-responders to MTX. Outcome measures At baseline and at every follow-up visits all PsA patients and controls were evaluated for the remission criteria as primary outcome measure. Secondary outcome measures were ACR 20, 50, 70 response criteria adapted to peripheral PsA by adding DIP evaluation, tender and swollen joints count, number of painful enthesis, number of digits showing dactylitis, ESR and CRP. Radiological examination of involved joints was carried out in all study patients and controls at baseline and every 2 yrs. Patients with additional clinically involved joints underwent to radiological examination at symptom onset and every 2 yrs.

3 874 F. Cantini et al. Follow-up Patients were followed by the same rheumatologist, and follow-up visits were scheduled at baseline and every 4 months. Control visit intervals were shortened in the case of urgent clinical problems, and all patients were instructed to call the centre in presence of worsening of previous arthritis, additional joint involvement, extra-articular manifestations onset and adverse events (AEs). At every visit, patients had a complete physical examination including all previously listed outcome measures. Moreover, routine blood examinations including ESR, CRP, RF, complete blood cell count with differential count, renal and liver function tests and ANA were carried out. All clinical and laboratory data were recorded in a computed patients chart. AEs At every visit, all patients were monitored for clinical and laboratory evidence of AEs defined as mild (transient and easily tolerated), moderate (subject discomfort with interruption of usual activities) and severe (incapacitating or life-threatening). The end of follow-up was extended to December The local ethic committee reviewed and approved the study protocol and its amendment. Before entering the trial each patient was informed of the nature, duration and purpose of the study, as well as of all the potential benefits and drawbacks that could be expected. All participants gave written informed consent. Statistical analysis Descriptive statistics and statistical differences were calculated using SPSS statistical package version 11 for Windows (SPSS Inc., Chicago, IL, USA). t-test for continuous variables and chi-squared test for nominal variables were used to calculate the differences between the study patients and controls, and between patients with PsA with and without remission. The correlation between the initial independent variables and remission rate was made with multiple logistic regression analysis. The following variables were analysed: age, gender, disease duration, pain severity, fatigue, number of involved joints, articular morning stiffness duration, ESR and CRP values, dactylitis, number of painful entheses, tenosynovitis and extra-articular features occurrence. With the exception of gender, absence or presence of tenosynovitis, dactylitis and extraarticular features, all variables were categorized into three groups according to tertiles of distribution. P-values <0.05 were accepted as statistically significant. Results During the 6-yr period, 388 new outpatients with all types of PsA were observed. Peripheral PsA requiring second-line drugs was diagnosed in 256/388 (65.9%) patients. As five patients were excluded on the basis of exclusion criteria, 251 patients were recruited for the study. Of these, 171 (68.1%) patients received traditional DMARDs, and 80 (31.8%) anti-tnf- drugs. Moderate to severe AEs requiring the interruption of therapy occurred in 9/251 (3.6%) patients. Of these, five occurred in PsA patients treated with traditional DMARDs (two generalized cutaneous rashes requiring hospitalization, one severe abdominal pain with diarrhoea, two bacterial pneumonitis), and four in those receiving anti-tnf- agents (two severe cutaneous rashes, one bacterial pneumonitis and one septic shoulder arthritis). Minor AEs not requiring therapy suspension, including nausea, headache, hypertrichosis, hypotension, abdominal cramps, mild liver enzymes elevation and upper respiratory infections were observed in 38/174 (21.8%) of PsA patients treated with traditional DMARDs and in 12/77 (16.2%) of patients receiving anti-tnf agents (P ¼ NS). Since 6/251 (2.4%) patients were lost during the follow-up, the final evaluation was made on 236 PsA patients. Psoriasis preceded articular symptoms in 154/236 (65%) patients, it was concomitant in 49/236 (21%) and posterior in 33/236 (14%). Over the same period 285 patients with RA were seen, of whom 268 were available for the study. Indeed, 7/285 (2.4%) patients with RA interrupted the treatment for drug related AEs, and 10 (3.5%) were lost during the follow-up. As shown in Table 2, the baseline demographic and clinical characteristics did not differ significantly between the two groups with the exception of the occurrence of dactylitis, enthesitis and tenosynovitis, which, as expected, were more frequent in PsA patients. As regards the treatment, 121 (51.3%) PsA patients received MTX alone, 39 (16.5%) MTX combined to CsA and 76 (32.2%) anti-tnf-. Of patients with RA, 198 (73.9%) were treated with MTX alone and 70 (26.1%) with anti-tnf-. Anti-TNF- were administered in association with MTX in both groups. As shown in Table 3, the mean follow-up was of months for PsA group and months for controls, with no significant difference. One or more episodes of remission were TABLE 2. Baseline demographic, clinical characteristics and treatment of 236 casepatients and 268 controls observed over a 6-yr period PsA RA P-value Patient (n) NS Gender (female/male) 102/ /93 NS Age (yrs) NS Disease duration (months) NS Fatigue (VAS mm) NS Pain (VAS 1 100) NS Articular morning stiffness (min) NS Tender joint count (n) NS Swollen joint count (n) NS ESR (mm/h) NS CRP (mg/dl) NS Patients with dactylitis, n (%) 46 (19) 0 (0) Patients with enthesitis/tenosynovitis, n (%) 74 (31) 12 (4.5) Patients with extraarticular features, n (%) 18 (7.6) 10 (3.7) NS MTX, n (%) 121 (51.3) 198 (73.9) <0.02 MTXþCsA, n (%) 39 (16.5) Anti-TNF-, n (%) 76 (32.2) 70 (26.1) NS Except where otherwise indicated, data are expressed as mean S.D; NS: not significant. TABLE 3. Treatment, frequency of remission and ACR 20, 50, 70 criteria response rate in patients with peripheral PsA and controls at the end of follow-up PsA 236 patients RA 268 patients P Patients with remission, n (%) 57 (24.1) 20 (7.4) <0.001 Overall remission, n (%) <0.001 MTX, n (%) 23 (29.9) 12 (50) NS MTXþCsA, n (%) 8 (10.4) Anti-TNF, n (%) 46 (59.7) 12 (50) NS Remission duration (months) ( S.D.) <0.001 Overall ACR 20 (%) NS ACR 50 (%) NS ACR 70 (%) NS MTX ACR 20 (%) NS ACR 50 (%) NS ACR 70 (%) NS MTXþCsA ACR 20 (%) 45 ACR 50 (%) 23 ACR 70 (%) 6 Anti-TNF ACR 20 (%) NS ACR 50 (%) NS ACR 70 (%) NS Follow-up duration (months) ( S.D.) NS

4 Remission in PsA 875 TABLE 4. Comparison of baseline demographic and clinical characteristics of 236 patients with peripheral PsA with and without remission Remission group Non-remission group Patients (n) <0.001 Gender (female/male) 31/46 71/88 NS Age (yrs) ( S.D.) NS Disease duration (months) ( S.D.) NS Fatigue (VAS mm) ( S.D.) NS Pain (VAS 0 100) ( S.D.) NS Articular morning stiffness (min) ( S.D.) NS Tender joint count (n) ( S.D.) NS Swollen joint count (n) ( S.D.) NS ESR (mm/h) ( S.D.) NS CRP (mg/dl) ( S.D.) NS Patients with dactylitis, n (%) 12 (15.5) 34 (21.3) NS Patients with enthesitis/ 22 (28.5) 52 (32.7) NS tenosynovitis, n (%) Patients with extraarticular features, n (%) 4 (5.1) 14 (8.8) NS TABLE 5. Period frequency and off-therapy duration of clinical remission in PsA and controls PsA RA P Patients (n) Patients with remission, n (%) 37 (50.7) 8 (11.2) <0.001 Overall remission (n) <0.001 MTX, n (%) 9 (20.4) 5 (41.7) NS Anti-TNF-, n (%) 35 (79.5) 7 (58.3) NS Remission duration (months) ( S.D.) <0.001 Follow-up duration (months) ( S.D.) NS observed in 57/236 (24.1%) of PsA patients and in 20/268 (7.5%) of controls (P < 0.001). In PsA group 40 (70.2%) patients had one episode of remission, 14 (24.6%) two episodes and 3 (5.3%) three episodes, while in RA group 16 (80%) patients experienced one episode and 4 (20%) two episodes. Therefore, the overall frequency of clinical remission episodes in study patients and controls was respectively of 77 in PsA patients and 24 in controls (P < 0.001). The mean duration of remission was of months in PsA patients and of in controls (P > 0.001). No significant differences resulted regarding the baseline demographic and clinical characteristics of PsA patients with and without clinical remission (Table 4). We also calculate the percentage and the duration of clinical remissions dividing by the two different treatment groups: 31 episodes of remissions were observed in 160 PsA patients of traditional DMARDs group and 46 in 76 patients of anti-tnf- group (P < 0.001). No significant difference was recorded as regards the duration of remissions between the traditional DMARDs group and anti-tnf group: and months (P ¼ NS). According to the protocol, from January 2003 to December 2005 therapy was suspended in PsA patients and controls if they achieved clinical remission. As summarized in Table 5, over this period 37 (50.7%) out of 73 PsA patients and 8 of 71 controls experienced at least 1 episode of remission. The total number of remissions were 44 in 73 PsA patients and 12 in controls (P < 0.001). The frequency of remission in PsA patients was significantly higher in those treated with anti-tnf- drugs compared with those treated with MTX alone (79.5% vs 20.4%; P < 0.001). The duration of remission after therapy interruption was of months for PsA group and months for patients with RA (P < 0.001). The duration of remission was not significantly different in PsA patients who interrupted the therapy with respect to those who received continuous treatment ( vs months; P ¼ NS). P Multiple logistic regression analysis did not disclose any significant association with remission for all variables at presentation including age, gender, disease duration, pain severity, fatigue, number of involved joints, articular morning stiffness duration, ESR and CRP values, dactylitis, number of painful enthesis, tenosynovitis and extra-articular features occurrence. Discussion PsA is used to be considered a relatively mild non-deforming arthropathy. However, this view has been challenged over the last two decades. The development of erosive and deforming arthritis in 50% of the cases has been demonstrated in several large clinical series, and consequently the therapeutic strategies have been changing over time [6, 7, 30, 31]. Second-line drugs such as SSZ, CsA, MTX, LEF and more recently anti-tnf- drugs have been added to the previous standard treatment mainly based on local infiltrative therapy, NSAIDs and CS [15, 16, 32, 33]. Similarly to RA, in all studies, the response to therapy was evaluated in terms of percentage of responders through different validated outcome measures, but in none the frequency of clinical remission constituted a primary or secondary end-point. Remission criteria for RA have been formulated in 1981 by the ACR [21]. A few studies have evaluated the frequency of remission in longstanding RA using the ACR criteria: in patients taking DMARDs a remission rate ranging from 4.1% to 18% resulted from four large series [34 37]. No remission criteria have been standardized for PsA. To our knowledge, only a few studies focused on clinical remission in PsA. In 2001, Gladman et al. [20] reported 69/391 (17.6%) patients with PsA receiving medications and with a mean disease duration of 12.7 yrs who achieved the clinical remission, with a mean duration of 2.6 yrs. Of these, 20 patients (29%) were drug-free. In this study, remission was defined as a period of at least three consecutive visits with absence of actively inflamed joints, independently on other clinical and laboratory parameters. Two years later, Kane et al. [7] reported a remission frequency of 26% at 1 yr, and of 21% at 2 yrs of follow-up in 129 patients with early PsA, with a remission rate in DMARD-free subjects of 12% at 1 yr and 11% at 2 yrs. Clinical remission was assessed using the ACR remission criteria for RA [21]. Recently, in a 26-week observational study, 4 (25%) out of 20 patients with refractory PsA treated with etanercept achieved a complete remission [38], defined as absence of tender and swollen joints. These studies are not comparable due to the different study populations and remission criteria employed, that might have negatively influenced the results. Criteria for remission used by Gladman et al. [20] considered only the actively inflamed joint count for at least three consecutive visits scheduled every 6 months, with no mention of other typical and frequent PsA manifestations including tenosynovial and entheseal involvement. Moreover, the 6-month interval between the visits did not allow to assess remissions lasting <12 months. Equally, the ACR remission criteria for RA adopted in Kane s study [7] do not seem adequate for peripheral PsA patients: this set of criteria focuses on the clinical aspects of RA and does not encompass the different clinical features of PsA, such as distal IP joint involvement, dactylitis, enthesitis and extra-articular features. Owing to these considerations, in our study we modified the ACR remission criteria to more accurately evaluate the clinical remission in patients with peripheral PsA. Despite this more restrictive set of criteria, 57 out of 236 (24.1%) patients of PsA group experienced one or more episodes of remission with an overall number of 77 episodes, with a significant difference with respect to RA controls (P < 0.001). Also, significantly different was the duration of remission in PsA patients compared with those with RA ( vs months; P < 0.001).

5 876 F. Cantini et al. The remission episodes were significantly higher in patients receiving anti-tnf- drugs compared with those treated with traditional DMARDs (P < 0.001), with no differences in the mean duration of remission. Therefore, in terms of clinical remission, peripheral PsA seems to respond better than RA either to traditional DMARDs or anti- TNF agents, suggesting a different disease severity between the two diseases. This seems to be confirmed by the significantly longer duration of remission in patients with PsA compared with those with RA observed in our study. Confirming the report of Gladman et al. [20], our study indicates that, differently from RA, a consistent percentage of subjects with PsA, treated either with traditional DMARDs or anti-tnf, maintains the remission for a prolonged time (mean 12 2 months) after therapy interruption, without differences in the duration with respect to those without interruption. This finding may suggest an intermittent treatment for a considerable percentage of patients, with relevant lowering of economic and safety burden. A criticism to our study may be related to the selection of patients. PsA is characterized by a wide spectrum of disease severity and patients with mild, non-evolutive disease have been identified [39]. This might have produced a selection bias determined by the inclusion of PsA patients who have a disease course milder than that of RA. However, to reduce this risk and to evaluate a homogeneous group of PsA patients with more severe disease, we recruited only patients with peripheral PsA requiring DMARDs or anti-tnf therapy. In conclusion, our study shows that long-term episodes of remission are possible in up to 24% of patients with peripheral PsA. The frequency of remissions is significantly higher in patients receiving anti-tnf drugs, although no differences were observed as regards the duration compared with those receiving traditional DMARDs. Finally, patients still remain in remission for a long period after therapy interruption, thus suggesting an intermittent therapeutic strategy. Acknowledgements We would like to thank very much the Rheumatology Unit of Prato health professionals, Mrs Domenica Rochira, Mrs Maddalena Fattibene, Mrs Sabrina Guarducci, Mrs Alessandra Bartolozzi and Mrs Erica Gheri for their continuous efforts to ensure a good quality care to all patients and for helping us to record patients data. Disclosure statement: The authors have declared no conflicts of interest. References Rheumatology key messages Long-term episodes of remission are possible in up to 24% of patients with peripheral PsA. The frequency of remissions is significantly higher in patients receiving anti-tnf drugs compared to those treated with traditional DMARDs. No differences were observed as regards the duration of remission between patients receiving anti-tnf or traditional DMARDs. 1 Moll JMH, Wright V. Psoriatic arthritis. Semin Arthritis Rheum 1973;3: Jones SM, Armas JB, Cohen MG, Lovell CR, Evison G, McHugh NJ. Psoriatic arthritis: outcome of disease subsets and relationship of joint disease to nail and skin disease. Br J Rheumatol 1994;33: McNugh NJ, Balachristian C, Jones SM. Progression of peripheral joint disease in psoriatic arthritis: a 5-year prospective study. Rheumatology 2003;42: Khan M, Schentag C, Gladman DD. Clinical and radiological changes during psoriatic arthritis disease progression. J Rheumatol 2003;30: Kammer GM, Soter NA, Gibson DJ, Schur PH. Psoriatic arthritis: a clinical, immunologic and HLA study of 100 patients. Semin Arthritis Rheum 1979;9: Gladman DD, Schuckett R, Russell ML, Thorne JC, Schachter RK. Psoriatic arthritis (PSA): an analysis of 220 patients. Q J Med 1987;62: Kane D, Stafford L, Bresnihan B, Fitzgerald O. A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience. Rheumatology 2003;42: Gladman DD, Farewell VT, Nadeau C. Clinical indicators of progression in psoriatic arthritis: multivariate risk model. J Rheumatol 1995;22: Queiro-Silva R, Torre-Alonso JC, Tinture-Eguren T, Lopez-Lagunas I. A polyarticular onset predicts erosive and deforming disease in psoriatic arthritis. Ann Rheum Dis 2003;62: Gladman DD, Farewell VT, Kopciuk K, Cook RJ. HLA antigens and progression in psoriatic arthritis. J Rheumatol 1998;25: Punzi L, Pianon M, Rossini P, Schiavon F, Gambari PF. Clinical and laboratory manifestations of elderly onset psoriatic arthritis: a comparison with younger onset disease. Ann Rheum Dis 1999;58: Balding J, Kane D, Livingstone W et al. Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity. Arthritis Rheum 2003;48: Salvarani C, Cantini F, Olivieri I. Disease-modifying antirheumatic drugs therapy for psoriatic arthritis. Clin Exp Rheumatol 2002;20(Suppl 28):S Salvarani C, Olivieri I, Cantini F, Macchioni P, Boiardi L. Psoriatic arthritis. Curr Opin Rheumatol 1998;10: Gladman DD. Effectiveness of psoriatic arthritis therapies. Semin Arthritis Rheum 2003;33: Nash P, Clegg DO. Psoriatic arthritis therapy: NSAIDs and traditional DMARDs. Ann Rheum Dis 2005;64:ii Kaltwasser JP, Nash P, Gladman DD et al. Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: a multinational, double-blind, randomized, placebo-controlled clinical trial. Arthritis Rheum 2004;50: Mease PJ, Antoni CE. Psoriatic arthritis treatment: biological response modifiers. Ann Rheum Dis 2005;64: Soriano ER, McHugh NJ. Therapies for peripheral joint disease in psoriatic arthritis. J Rheumatol 2006;33: Gladman DD, Tung Hing ENG, Schentag CT, Cook RJ. Remission in psoriatic arthritis. J Rheumatol 2001;28: Pinals RS, Masi AT, Larsen RA. Preliminary criteria for clinical remission in rheumatoid arthritis. Arthritis Rheum 1981;24: Harrison BJ, Symmons DP, Brennan P, Barrett EM, Silman AJ. Natural remission in inflammatory polyarthritis: issues of definition and prediction. Br J Rheumatol 1996;35: Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31: Felson DT, Anderson JJ, Boers M et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 1995;38: Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis: a proposal for modification of the New York criteria. Arthritis Rheum 1984;27: Mander M, Simpson JM, McLellan A, Walker D, Goodacre JA, Dick WC. Studies with an enthesis index as a method of clinical assessment in ankylosing spondylitis. Ann Rheum Dis 1987;46: Calin A, Porta J, Fries JF, Schurman DJ. Clinical history as a screening test for ankylosing spondylitis. JAMA 1977;237: Cantini F, Salvarani C, Olivieri I et al. Erythrocyte sedimentation rate and C-reactive protein in the evaluation of disease activity and severity in polymyalgia reumatica: a prospective follow-up study. Semin Arthritis Rheum 2000;30: Sheldon J. Laboratory testing in autoimmune diseases. Best Pract Res Clin Rheumatol 2004;18: Gladman DD, Stafford-Brady F, Chang CH, Lewandosky K, Russel ML. Longitudinal study of clinical and radiological progression in psoriatic arthritis. J Rheumatol 1990;17: Gordon DA, Stein JL, Broder I. The extra-articular features of rheumatoid arthitis: a systematic analysis of 127 cases. Am J Med 1973;55: Jones G, Crotty M, Brooks P. Psoriatic arthritis: a quantitative overview of therapeutic options. The Psoriatic Arthritis Meta-Analysis Study Group. Br J Rheumatol 1997;36: Mease PJ, Antoni CE. Psoriatic arthritis treatment: biological response modifiers. Ann Rheum Dis 2005;64(Suppl II):ii Wolfe F, Hawley DJ. Remission in rheumatoid arthritis. J Rheumatol 1985; 12: Prevoo MLL, van Gestel AM, van t Hof MA, van Rijswijk MH, van de Putte LBA, van Riel PLCM. Remission in a prospective study of patients with rheumatoid arthritis. American Rheumatology Association preliminary remission criteria in relation to the disease activity score. Br J Rheumatol 1996;35: Sokka T, Pincus T. Most patients receiving routine care for rheumatoid arthritis in 2001 did not meet inclusion criteria for most recent clinical trials or American College of Rheumatology criteria for remission. J Rheumatol 2003;30: Balsa A, Carmona L, Gonzalez-Alvaro I, Belmonte MA, Tina X, Sanmarti R. Value of DAS 28 and DAS 28-3 as compared to ACR-defined remission in rheumatoid arthritis. J Rheumatol 2004;31: de Vlam K, Lories RJ. Efficacy, effectiveness and safety of etanercept in monotherapy for refractory psoriatic arthritis: a 26-week observational study. Rheumatology 2006;45: Salvarani C, Cantini F, Olivieri I et al. Isolated peripheral enthesitis and/or dactylitis: a subset of psoriatic arthritis. J Rheumatol 1997;24: