In this study, we investigated gender differences in biologic treatment by examining disease characteristics at the time of biologic initiation in RA, IBD, and psoriasis. We found that there was a treatment difference in both IBD and psoriasis, with men receiving biologic medication more often than women. With regard to the disease characteristics, we found that women with RA or IBD had higher scores than men on subjective but not on objective measures. Only for psoriasis did men score higher on objective disease measurements.
Thus, the greater proportion of men receiving biologic treatment for IBD or psoriasis compared with women was not reflected in the population prevalence rates, which were similar for both sexes in both diseases. This in contrast to RA, for which treatment and population male:female ratios matched each other. For RA, our data confirm earlier studies that did not note any gender differences in the overall use of biologic medications [5, 7, 30, 31]. For both psoriasis and IBD, it had previously been suggested that males are more likely than women to receive systemic treatment (biologic or non-biologic) [32, 33], and in the case of psoriasis that female patients are more likely to receive topical treatment whereas men are more likely to receive phototherapy .
The gender difference we found in treatment proportions for men and women with IBD or psoriasis gives rise to a number of hypotheses that could explain these findings. Possible reasons that more men than women are treated with biologics include the following: men have more severe disease activity; men may be more likely than women to express treatment preferences for biologics/systemic agents; there may be gender differences in treatment access; the risk:benefit ratio as determined by the physician may be modified by the patient's gender; or there may be a gender difference in the effectiveness of biologicals and of treatment alternatives. With respect to the last point, an interesting point was made by Nyberg et al., who suggested that females are more likely to believe that they can influence their disease themselves and therefore tend to assume or be given greater responsibility for their disease (that is, are prescribed more self-care topical treatment) . Later in-depth interviews showed the same tendency . This could mean that through more and better use of an alternative treatment, women with psoriasis need biologic treatment less often than men. Because some patients in this psoriasis cohort were already using biologics at inclusion, similar effects with better adherence to oral medication by women might have influenced PASI scores. However, to our knowledge no reports exist to support this hypothesis. With regard to the risk:benefit ratio, biologic therapies might be considered more dangerous for young women of childbearing age than for men because of possible teratogenic effects, although for biologics this is not yet proven [36, 37]. This concern, in combination with age differences, might have been an influence on the discrepant gender ratio for biologic treatment in IBD and psoriasis, as the female patients with RA were on average 20 years older than their IBD and psoriasis counterparts when started on biologics (54.6 for RA versus 35.4 years for IBD and between 20 and 40 years for psoriasis ).
With regard to the disease characteristics pertaining before biologic therapy initiation, significant gender differences were found for both RA and psoriasis, and similar numerical differences were found for IBD. At treatment start, female patients with RA had higher values for ESR, patient global assessment, TJC, HAQ, DAS28, and DAS28CRP compared with men. One study on anti-TNF therapy  found a similar gender imbalance in objective and subjective measurements as we found in this study. Furthermore, recent data from Arkema et al, from the Anti-Rheumatic Therapies in Sweden (ARTIS) registry also support a difference in subjective disease parameters for patients with RA starting biologic therapy. Most studies on gender in RA used time points other than biologic initiation, but the results parallel ours [3–6, 40].
Because biologic medications are now used earlier in the disease course than at the time these therapies were first introduced, this could possibly induce gender differences. However, we did not find such evidence, and this is in line with similar studies . The differences in TJC and SJC are not large, they could nonetheless be important when studied at group level. Furthermore, measurements of TJC and SJC in rheumatology practice in the hospital system in which these patients were seen are highly standardized (based on the European League Against Rheumatism handbook) so that interobserver variability is minimized. Another confounder could be a gender difference in the specific joints that are inflamed, but as the individual joints are not recorded in the STURE database, this question remains open.
In psoriasis, a gender difference was found for both the PASI and the DLQI, with men more often having high PASI scores and women more often having high DLQI scores. Our findings for the DLQI parallel a few, but not all, studies on QOL in psoriasis [18–20, 41]. For IBD, the SHS, which can be regarded as a short QOL assessment, tended to be higher in women. This matches earlier research in which female gender was found to be a predictor of impaired HRQOL and level of concern [42–44].
Although different assessments were used for the three diseases, a general comparison can be made in that in all three diseases the gender imbalance seems to occur only in subjective measurements such as pain, functional status, and QOL. These results support the hypothesis that the inherent biology of the diseases is similar for both genders, but that females experience their illness as worse, and consequently have a higher symptomatic disease burden. For RA, this is further supported by a study in which women were shown to have more symptoms than men despite similar radiographic joint damage . The higher ESR in female patients with RA could be an exception, but women are known to have higher ESR levels than men, which is most likely due to hormonal factors and a difference in hematocrit concentration [39, 45].
The literature regarding gender differences in RA has focused on the possible non-sex neutrality of the disease activity measurements used. For psoriasis and IBD, the same questions may apply. Pain and related measurements are often discussed as being non-sex-neutral. Women are more likely than men to experience different kinds of recurrent pains and also to report more severe levels of pain [46, 47]. Moreover, with the same noxious stimuli, women experience more pain than men . These factors can consequently influence pain measurements (TJC, global pain), assessments in which pain is included (DAS28, SHS symptoms, HBI) or assessments that are affected by pain (HAQ, DLQI, SHS). In the case of RA, concomitant fibromyalgia could also influence pain measurements .
Another example is the HAQ score, which is known to be higher in females with RA [5, 6, 30, 50]; and this could be attributable to the fact that women have less muscle strength, but it is also possible that men overestimate their functional capacity or that women have higher pain scores [30, 48]. Therefore the higher HAQ scores might be caused by the properties of the HAQ rather than by RA; however, it is interesting to note that in the healthy population, no sex differences in HAQ scores are seen [51, 52].
Although not formally studied, the PASI might also be influenced by gender. The component of 'scaling' is immediately improved after the use of emollients, and even experienced scorers would probably give a lower score for a skin that has just been treated with emollients. As stated earlier, women are more likely than men to adhere to topical treatment, and consequently, this could mean systematic underscoring of the PASI in female patients.
Thus, it is not clear whether standard disease assessments are sex-neutral, but there is also another way of looking at this question. For example, if women do feel more pain with the same stimulus can it then really be said that the disease is the same? Are fewer compensation resources sufficient reason to disregard a gender difference? It would seem that the subjective disease experience may to some extent be discounted by physicians, whereas for the patient this may be the most important part of their disease.
In summary, we found gender differences in disease characteristics at the start of biologic or systemic treatment in RA, IBD, and psoriasis, with an over-representation of men in the latter two diseases, and greater effect of the disease and worse QOL scores in women with all three diseases. This suggests a potential subtle undertreatment of women with these diseases. We note that undertreatment in RA might then also partly explain the worse outcomes previously reported in longitudinal studies for women with RA.
This study has several limitations, as it was a retrospective observational study with all data having been collected at clinical visits. In addition, it must be noted that the psoriasis results came from an annual report, and were not computed using the raw data. Furthermore, some of the measurements in psoriasis were performed after treatment initiation, and thus the real gender difference might therefore be even bigger. The PASI and DLQI scores were given only for the total group, and not separately for each treatment, therefore subgroup analysis was not possible, thus making comparison with RA and IBD more difficult.