The use of biological drugs is therefore an exciting new approach to 3-Methylsalicylic acid fatigue treatment in chronic inflammatory diseases. This class of drugs may influence fatigue generating pathways. Several studies point to an influence of IL-1 on mood and depression. Depressed patients were excluded from the current study because we wanted to explore the influence of IL-1 on fatigue in non-depressed patients. However, we believe it would be of great interest to map the effects of newer biological drugs on depression. Future studies of biological drugs in pSS should ideally include measures of both fatigue and depression. There are several limitations to this study. The number of subjects is small; reflecting the difficulty in selecting patients not biased by depression, drugs, or other factors that could influence fatigue. The patients included may not represent the whole pSS cohort, as the percentage of male patients was higher than expected, and most patients were using at least one disease modifying drug. Also, we used a simple randomisation, which may have lead to unbalanced arms. In a small study like this it would at best be possible to stratify the subjects on one, possibly two variables. However, it is not clear which variables are the optimal ones to employ. There is no known association in pSS between fatigue and age, disease duration, laboratory values or other clinical parameters that could be used for stratification at inclusion. Neither did we stratify according to fatigue score, as FSS.3 was a criteria for inclusion. For this reason, we decided a 1:1 allocation was the best approach. We did not investigate the relationship between social factors and fatigue, as the small patient number did not allow subgroup analysis. We used two instruments to measure fatigue; the fatigue VAS and the FSS. Both of these scales are unidimensional, and the use of a multidimensional scale might have provided extra information on the origin of fatigue. The placebo effect was quite strong in this study, as both groups had a reduction in fatigue at week 2 close to significance. This is not unexpected. Figure 2 illustrates how the placebo group reported more fatigue at week 4, while the treatment group had a further decline in fatigue. We interpret this as a reduction in the placebo-effect at week 4. We did not measure pSS disease activity during the study. The lack of a disease activity instrument that is sensitive to change has been a limitation in intervention studies of pSS patients. Recently an instrument for this purpose was developed and it is reportedly accurate in detecting changes in disease activity. Local skin reactions are common following Gambogic-acid anakinra injections and are well known to patients. Thus, some patients may have guessed their allocated treatment; we can not exclude the possibility that this may have affected the final results. However, two of the patients in the placebo group also reported skin reactions.