The introduction of biological drugs represents a major progress in the treatment of psoriatic arthritis, and has led to an increased interest in the disease. The efficacy of TNF‐blocking agents has been demonstrated through several randomised controlled trials.3,4,5
The efficacy of traditional DMARDs, by contrast, is poorly documented through systematic trials.6
Nevertheless, they are widely used, mainly based on the clinical impression that these drugs are effective. Systematic studies that explore the efficacy of traditional DMARDs in PsA, as well as the comparative efficacy between traditional DMARDs and biological treatments are in demand. In the present longitudinal observational study we compared the real‐life performance of MTX and TNF‐inhibitors in patients with PsA. Patients in both treatment groups in the present study improved, but the improvement was larger with TNF‐inhibitors compared to MTX (table 2).
Although the preferred design for studies addressing comparative efficacy is RCT, longitudinal observational studies can provide additional information of value as they are conducted in a patient population treated in a real‐life clinical setting. However, several biases complicate the analyses and interpretation of the results. One obvious limitation is the lack of randomisation and confounding by indication, which is one of the major challenges in observational studies, as treatment decisions depend on the condition of the patient at the time of inclusion. Propensity modelling is the contemporary method for statistical “semi‐randomisation”.20
The aim of the method is to identify important factors that predict the treatment decisions and then balance the groups with respect to these factors. Another challenge in observational studies is missing data. Data for the 6 month LOCF analyses was not available in 24 (6.3%) of the patients in the MTX group and 14 (9.6%) of the patients in the anti‐TNF group. A total of 108 (74%) of the patients in the anti‐TNF group had previously used MTX, and 39 of these patients were also included in the MTX group. However, when excluding the patients represented in both groups from the analyses, the results remained similar. Interestingly, the mean age in the TNF group was lower than the mean age in the MTX group, whereas disease duration was significantly longer. This might indicate a bias against using biological therapy in older persons.
The anti‐TNF group in our study comprises all patients using infliximab, etanercept and adalimumab, with or without concomitant MTX. We performed a subanalysis comparing the anti‐TNF monotherapy with the combination with MTX. These groups were similar with regard to baseline scores and changes from baseline, justifying that they were considered as one group. The finding corresponds with results from RCTs.4,5,21
Although no head‐to‐head comparisons have been performed between the different TNF‐blocking agents, similar magnitude of clinical response has been observed across trials with the different agents with respect to joint symptoms, whereas improvements in skin manifestations seem to be somewhat greater with the monoclonal antibodies.4,5,21
Only two minor RCTs with MTX for PsA have been conducted.7,8
In 21 PsA patients, of whom 10 received parenteral MTX, significant improvements in skin and joint symptoms were observed in the MTX group compared to the placebo group.7
The other placebo‐controlled trial with 37 patients failed to demonstrate superiority of orally administered MTX versus placebo for other measures than physician assessment of arthritis activity.8
In our study, the MTX group improved significantly from baseline for nearly all measures, although these results cannot be considered as any proof of the efficacy of MTX in PsA as a control group with placebo or a potentially less effective DMARD was not included.
Development and validation of assessment tools, as well as diagnostic and classification criteria, in PsA, is the focus of several initiatives lately.15
At the time of writing, no core set of assessments has yet been agreed upon. The limited joint count (28 joints) is a potential weakness in our study. Experts have different opinions with respect to the number of joints to be counted, but the composite measure DAS‐28 has been shown to be discriminant and responsive in placebo‐controlled clinical trials, whereas the 28 swollen‐ and tender joint counts per se showed less discriminative ability than more extensive joint counts.13
This is in accordance with the findings in our study, where the 28‐joint counts did not reveal differences between the groups, whereas the composite measure, DAS‐28, was significantly different at baseline and with regard to change. Several trials have demonstrated improved health related quality of life (HRQoL) in PsA treated with TNF‐blocking agents.4,5,22
In the IMPACT 2 trial22
the improvements in the 8 SF‐36 scores were comparable to the changes in the anti‐TNF‐group in the present study. Our study also showed that anti‐TNF treatment was superior to MTX in improving bodily pain, vitality, role physical and general health scores.
The cost‐effectiveness of etanercept compared to ciclosporin and leflunomide in PsA patients was recently explored by Bansback et al
They demonstrated, by modelling treatment over 10 years, that 0.82 and 0.65 more quality adjusted life years (QUALYs) were gained with etanercept as compared to ciclosporin and leflunomide, respectively, using the utility measure EQ‐5D. The utility measure SF‐6D, computed from the SF‐36 items, is used in NOR‐DMARD. We found that the 6‐month improvement in SF‐6D was 0.066 in the anti‐TNF group and 0.040 in the MTX group, with a between group difference of 0.026 QUALYs. These results are, however, not directly comparable as EQ‐5D usually results in a larger gain in QUALYs than SF‐6D due to different floor and ceiling effects of these instruments.24
A full set of domains to be assessed would ideally include skin involvement, dactylitis, enthesitis, spine involvement and radiological outcome. For feasibility reasons these assessments are not incorporated in the NOR‐DMARD register, thus all patients, irrespective of type of inflammatory arthropathy, are assessed by the same set of assessment tools. It appeared that individual core measures of disease activity for RA, the composite measure DAS‐28 as well as measures of HRQoL, differentiated between anti‐TNF drugs and MTX. For exploratory purposes we also looked at two recently developed composite measures for RA, the simplified disease activity index (CDAI)25
and the clinical disease activity index (SDAI (
CDAI + C‐reactive protein)).26
In this setting SDAI discriminated between the two treatment groups, whereas CDAI did not.
The diagnoses were made by the treating rheumatologists. About 6% of the patients were positive for rheumatoid factor (RF), and we cannot exclude that some of these patients had rheumatoid arthritis plus psoriasis. However, the percentage of RF positive patients was similar in the two groups.
The efficacy of TNF inhibitors in patients with PsA have been thoroughly explored in placebo‐controlled RCTs. This longitudinal observational study is to our knowledge the first study in which the comparative effectiveness of TNF inhibitors and MTX is assessed. Our conclusion is that PsA patients seem to benefit more from TNF‐blocking agents than MTX when treated in daily clinical practice. This result is consistent with findings in RCTs and contributes to improve external validity of results from RCTs examining anti‐TNF drugs in PsA. However, more studies are needed to further establish the role of traditional DMARDs in the treatment of PsA.