Treatment Options for the Comorbidity of Multiple Sclerosis with Other Chronic Inflammatory Diseases

Background: Approximately 280 000 people in Germany suffer from multiple sclerosis (MS), an autoimmune disease of the central nervous system. Of these, approximately 5% have a comorbid chronic inflammatory disease: the more common ones are psoriasis, rheumatoid arthritis (RA), and chronic inflammatory bowel diseases (IBDs, of which the main types are ulcerative colitis and Crohn’s disease).

Methods: This narrative review is based on pertinent publications retrieved by a literature search in PubMed, as well as relevant guidelines. All statements in this article reflect a consensus among the authors, who represent different medical disciplines.

Results: As the data from clinical trials to date are limited, judgments about the proposed treatments are a matter of expert opinion. In general, TNFα blockers should not be used in patients with MS, as they can worsen the disease. In patients with MS and psoriasis, dimethyl fumarate is a useful option for mild disease activity. In MS with comorbid RA, azathioprine and leflunomide/teriflunomide are suitable for mild disease activity. For more severe disease activity, anti-CD20 antibodies have been approved for both diseases and should be used. In MS with comorbid IBD, azathioprine is suitable for mild disease activity. Ozanimod has been approved for patients who have MS and comorbid ulcerative colitis with more severe disease activity, especially those who are JC-negative; it shares its mechanism of action (VLA-4 blockade) with natalizumab.

Conclusion: The treatment of patients who have both MS and another chronic inflammatory disease should be interdisciplinary and personalized, and treatments must be planned with due attention to potential adverse effects. Further studies of treatment for this group of patients are needed.

Cite this as:Bittner S, Kriegel MA, Siegmund B, Kümpfel T, Sabat R: Treatment options for the comorbidity of multiple sclerosis with other chronic inflammatory diseases. Dtsch Arztebl Int 2025; 122: 427–32; DOI: 10.3238/arztebl.m2025.0088.

Over the last few decades, significant advances have been made in the treatment of autoimmune diseases such as multiple sclerosis (MS) (1). An estimated 5% of patients with MS have a comorbid chronic inflammatory disease (2, 3, 4). Surveys from the years 2012–2022 on the prevalence of autoimmune diseases in Germany found psoriasis (approx. 1 :  50), rheumatoid arthritis (RA; approx. 1 :  70) and inflammatory bowel disease (IBD; approx. 1 :  130) ranking highest, followed by MS on rank 8 (approx. 1 :  275) (5). Given the considerable absolute number of cases and the therapeutic relevance of these conditions, our narrative review focusses on the diseases mentioned above.

The occurrence of various chronic inflammatory diseases is frequently associated with an increased risk of suffering from a further immune-mediated disease; this is to some extent attributable to disease-spanning genetic risk factors and environmental risk factors (6, e1). For example, two large cross-sectional cohort studies, each including more than 20 000 patients, found for the additional diagnosis of MS a relative risk increase of 1.54–2.09 and 1.75–2.35 for Crohn‘s disease and ulcerative colitis, respectively (7, 8). In female and male patients with MS, comparable risk increases were noted for developing psoriasis (hazard ratio [HR] 1.92 and 1.54, respectively) or RA (HR 1.78) (4, 9, 10, 11). The clinically relevant pathogenic mechanisms underlying the various chronic inflammatory diseases overlap to some extent. Thus, there is reason to hope that in future medications will be developed that can treat several autoimmune diseases simultaneously.

When confronted with signs and symptoms of chronic inflammatory diseases in everyday clinical practice, it is important to take the following into account:

• Since various immune-related diseases show multiple organ system involvement, another underlying disease may cause the central nervous system symptoms. In this review article, we only address the coexistence of MS with one further chronic inflammatory disease.
• Once the disease has been classified based on a differential diagnostic work-up (including, for example, magnetic resonance imaging, cerebrospinal fluid analysis, laboratory testing) and interdisciplinary case conferences, specific treatment concepts should be prepared. Ideally, it is possible to use medications that have positive effects on both diseases. In the case of combination therapies, particular attention should be paid to a potential augmentation of side effects.

There is also the possibility of opportunistic infections. In 2006, for example, the anti-α4 integrin antibody natalizumab was the first monoclonal antibody to be tested in patients with MS in combination with interferon-beta, the standard of care at that time (12). During the trial, cases of progressive multifocal leukoencephalopathy (PML) were observed. This very severe infection of the brain is caused by the John Cunningham (JC) virus. We now know that in JC virus-positive patients the risk of developing PML is increased by natalizumab administration in particular due to interactions of the drug with the normal immunosurveillance of the brain (13). Sporadic cases of PML have been reported with many other immunosuppressive treatments. Currently, more than 15 medications in total are available for the treatment of MS. Their use is primarily guided by the clinical course of the disease (relapsing remitting or progressive), the disease activity and co-factors such as age, comorbidities, mode of application, patients‘ preferences, and family planning (Table 1). The aim of this review is to present recommendations for the management of MS patients with comorbid psoriasis, RA or IBD.

Table 1

Disease-spanning pharmacological approaches to multiple sclerosis and comorbid chronic inflammatory diseases

Rather than covering the full range of all approved medicines, our review focuses on the most important medications used to treat these diseases. For a comprehensive overview, please refer to the systematic reviews published in English (14, 15). Due to the limited available evidence, the treatment options suggested in the following are to be classed as expert opinions.

Methods

This review is based on pertinent publications retrieved by a literature search in the PubMed database, using the keywords “multiple sclerosis“, “comorbidities“, “autoimmune diseases“, “psoriasis“, “chronic inflammatory bowel disorders“, “colitis“, and “rheumatoid arthritis“. Our search focused on clinical (randomized) trials, case studies and systematic reviews. The authors of this review then evaluated and summarized these publications and contributed their own clinical experiences as well as their immunological and pathophysiological knowledge.

Results

Multiple sclerosis and psoriasis

The cytokine interleukin-17A (IL-17A) is involved in the pathogenesis of both MS and psoriasis (e2). IL-17A is an immunomediator, mainly affecting the biology of epithelial cells; it is induced by IL-23 in defined immune cell populations (e3). Inhibiting the effect of IL-17A, e.g., by administering neutralizing antibodies, reduced skin symptoms by more than 75% in about 85% of patients with psoriasis (16).

Treating psoriasis with cortisone-containing topical medications is not contraindicated in patients with MS. In MS patients with moderate psoriasis, dimethyl fumarate deserve particular attention as a shared pharmacological principle (Figure, Table 2). The therapeutic effect of fumarates on psoriatic lesions was already discovered in the late 1950s (e4); about 50 years later, fumarates were introduced as dimethyl fumarate into the treatment of MS (17, 18). Various disease-specific oral formulations are available which have been approved for the treatment of either mild/moderate relapsing-remitting MS or moderate/severe psoriasis. Case reports indicate that fumarates can be used in patients with MS who also suffer from psoriasis (19, 20).

Figure

Drugs approved for the treatment of multiple sclerosis and the evidence available regarding comorbid chronic inflammatory diseases

Table 2

Selected randomized controlled trials with special relevance for indication-spanning immunotherapy

The situation is somewhat more complicated in patients with either highly active MS or severe psoriasis/psoriatic arthritis where fumarates are insufficiently potent to control the disease activity. For the treatment of highly active relapsing-remitting MS, migration-inhibiting sphingosine-1-phosphate receptor (S1PR) modulators (fingolimod, ozanimod, ponesimod) are a drug class to be mentioned (e5). For psoriasis, positive data from a placebo-controlled phase II study evaluating ponesimod are available (21). In the case of active MS and psoriasis, a combination treatment with FU may be considered. Attention should be paid to the risk of PML, since sporadic cases of PML have been observed in patients treated with fumaric acid derivatives alone, but also with S1PR modulators, as well as the risk of prolonged severe lymphopenia and its consequences (Table 2).

Overall, it can be assumed that the anti-α4 integrin antibody natalizumab and B cell-depleting substances have no relevant effect on psoriasis (e2). A combination of natalizumab with fumaric acid derivatives or other oral immunosuppressive therapies should generally be avoided due to the PML risk associated with natalizumab treatment, especially in patients with positive JC virus antibody titers. After an individual risk-benefit assessment, particularly with regard to opportunistic infections, B cell-depleting substances (rituximab, ocrelizumab, ofatumumab, ublitixumab) can be combined with other treatments (see below). Sporadic case reports have described worsening of psoriasis or de-novo occurrence of psoriasis-like dermatitis in patients treated with CD20 antibodies (e5, e6, e7, e8, e9). If biological agents are indicated for the treatment of severe psoriasis, it is important to take into account that TNFα antagonists should generally be avoided in MS. TNFα is a pro-inflammatory key protein targeted in the treatment of numerous chronic inflammatory diseases (e10). However, inhibition of the TNFα signaling pathway can lead to the initial clinical manifestation of MS or exacerbation of an existing MS (22, 23, 24). Possible pathophysiological reasons include a genetic mutation in TNF receptor 1 in MS and the complex biology of TNFα (e11, e12). Thus, it is contraindicated to initiate treatment with TNFα antagonists in patients with MS and ongoing TNFα antagonist treatment should be discontinued in patients with coexisting MS.

Secukinumab is an anti-IL-17A antibody successfully used to treat moderate or severe psoriasis and psoriasis arthritis. It also showed positive trends in a phase II study evaluating patients with MS, even though the primary endpoint was not met (reduction of the cumulative number of new MRI lesions between week 4 and 24 : 49% [−10; 77], p = 0.087) (25). No further studies, e.g. with clinical endpoints, are available on the use of secukinumab in MS. Several case studies have now reported successful treatment of MS/psoriasis with secukinumab (14). To date, there have been no reports on the use of the anti-IL-17A antibody ixekizumab as well as anti-IL-17 receptor antibodies (brodalumab), anti-IL-17A/IL-17F antibodies (bimekizumab), and anti-IL-23 antibodies (risankizumab, mirikizumab, guselkumab, tildrakizumab) for the treatment of MS. Anti-IL-23 antibodies are highly effective in psoriasis: A reduction in skin symptoms by more than 90% can be expected in about 75% of patients. In addition, they have a modulating effect on the overall disease course (e2, 26). The anti-IL-12/IL-23 antibody ustekinumab has also been approved for the treatment of adult patients with moderate to severe plaque psoriasis who have not responded to other therapies, for whom other therapies are contraindicated, or who did not tolerate other therapies. For patients with MS, results of a phase II study are available (27) which found no positive effects on clinical and magnetic resonance imaging endpoints. Overall, it can be assumed that ustekinumab has no positive effect on MS, but does not cause any deterioration either.

Thus, after simultaneous fumarate treatment in patients with active psoriasis, simultaneous treatment with IL-17A antibodies is recommended as the next step of treatment escalation. If a highly effective treatment approach is needed for both MS and psoriasis, a combination therapy, consisting of B cell depletion (highly effective in MS—no positive effect on psoriasis) and anti-IL-17A treatment (evidence from case studies suggests effectiveness in MS—highly effective in psoriasis), is a treatment option available after careful consideration of the risks and benefits. When using two monoclonal antibodies, consideration should be given to potential risks, in particular the increased risk of severe infections. Close monitoring is required.

Multiple sclerosis and rheumatoid arthritis

In contrast to rheumatoid arthritis (RA), virtually no clinical experiences with combination therapies, consisting of different immunosuppressive agents, are available for the treatment of MS. Weight-adapted continuous therapy with oral glucocorticoids as basic therapy or treatment with glucocorticoid-sparing immunosuppressants, such as methotrexate and mycophenolate mofetil which are used in several other autoimmune diseases, are not used in MS (28). Likewise, a combination of monoclonal antibodies with oral glucocorticoids and/or a classic immunosuppressant, such as rituximab and methotrexate in rheumatoid arthritis, is rather not used in the treatment of MS.

In Germany, azathioprine is still formally approved for the treatment relapsing-remitting MS, even though it is rarely used today (28). Older small studies on the use of methotrexate in MS are available which suggest a (minor) positive effect on inflammatory activity (e13, e14). Azathioprine and methotrexate are also treatment options for RA or IBD with mild disease activity; here, a minor positive effect on MS can be expected (Figure).

Leflunomide is approved for the treatment of RA and psoriatic arthritis (29, 30). Clinical trials on teriflunomide have been conducted solely in MS. In patients with MS and coexistent RA with mild/moderate disease activity, this drug class (teriflunomide, leflunomide) is considered the medication of first choice.

In the case of higher disease activity, anti-CD20 B cell-depleting substances are another drug class effective in the treatment of both diseases. The medications ocrelizumab, ofatumumab and ublitixumab are approved for the treatment of MS, and rituximab is approved for RA treatment. In addition, randomized clinical trials are available for ocrelizumab and ofatumumab in RA and for rituximab in MS.

Ocrelizumab at a dose of 600 mg intravenously (after initial induction with twice a dose of 300 mg within a period of two weeks) at fixed six-month intervals is approved for the treatment of relapsing-remitting and primary progressive MS (31, 32). Three phase III trial have reported clinical and serological improvements with ocrelizumab in patients with RA (33, 34, 35). In these trials, however, doses of 200 mg and 500 mg ocrelizumab on day 1 and day 5 as well as after 24 and 26 weeks were administered via infusion. Both dosages reached the primary endpoints, defined as the proportion of patients with a 20% improvement according to the criteria of the American College of Rheumatology (ACR20) at weeks 24 and 48. However, adverse events involving serious infections (pneumonia and sporadic opportunistic infections) were more common with the 500 mg dose. In addition, ofatumumab for subcutaneous administration (20 mg) is also approved or the treatment of active MS. In phase III studies on patients with RA, subcutaneous and intravenous formulations of ofatumumab also showed a clinical effect (36).

In combination with methotrexate, rituximab has, as a CD20 antibody, been approved for the treatment of severe active RA after 51% (rituximab) versus 18% (placebo) of patients (p<0.0001) showed an ACR20 response after 24 weeks in a trial (e15). With rituximab, positive experiences in the treatment of MS have been made over many years. In a phase III trial, only 3% of patients with rituximab (versus 16% with dimethyl fumarate treatment) experienced a relapse (risk ratio 0.19; 95% confidence interval [0.06; 0.62], p = 0.006) (e16). In Germany, however, rituximab has not been approved for the treatment of MS and consequently its use is off-label. In the guideline “Multiple Sclerosis“, this topic is discussed in detail (28).

In principle, medications which belong to the drug class of anti-CD20 antibodies are the preferred choice for patients with MS and comorbid active RA. Initially, a monotherapy should be pursued. If this approach is not sufficiently effective, a combination therapy with methotrexate can be administered. In the case that other medications are used which are highly effective in the treatment of RA (30), it is important to bear in mind that TNFα antagonists are contraindicated for use in patients with MS (see above). Other treatments for rheumatoid arthritis target either the IL-6 receptor (tocilizumab, sarilumab) or IL-6 directly (olokizumab). Experiences with the use of these medications in MS are scare (e17). While individual case studies have reported a deterioration after tocilizumab treatment, there are also reports about patients who remained stable under treatment with anti-IL-6 antibodies (e18). Thus, treatment with anti-IL-6 antibodies may be considered on a case-by-case basis in MS patients with comorbid active RA, in particular in those with stable MS. In addition, cladribine should be taken into account, a purine analogue approved for the treatment of MS. It showed positive effects in patients with rheumatoid arthritis and psoriatic arthritis in small pilot series (e19, e20). To date, there is insufficient experience with Janus kinase inhibitors in patients with MS. This drug class is approved for the treatment of RA and to some extent also for psoriatic arthritis and IBDs.

Multiple sclerosis and inflammatory bowel disease

As a monoclonal anti-α4-integrin antibody, natalizumab inhibits lymphocyte migration both into the brain (via α4β1 integrin) and into the gut (via α4β7 integrin) (Figure). In phase III trials, natalizumab showed positive results both in patients with MS (e21, e22) and patients with Crohn‘s disease (e23). In Europe and the USA, the drug is approved for the treatment of MS; in JC-positive patients, however, the risk of PML must be taken into account. More information about the background and patient management is available elsewhere (13, 28, 37). While natalizumab is approved for the treatment of Crohn‘s disease in the USA, it is not approved for this indication in Europe due to safety concerns (PML). As a result, vedolizumab, a selective α4β7 antagonist, was developed. It is approved for the treatment of ulcerative colitis (38) and Crohn‘s disease (39).Given the gut-selective effect of vedolizumab, there is no PML risk; however, no positive effect on MS is to be expected either. Thus, natalizumab represents a therapeutic principle with multiple effects; the drug is particularly useful in JC virus-negative patients.

Other migration inhibitors also show clinically relevant overlapping effects. S1PR modulators inhibit the egress of lymphocytes from secondary lymphoid organs. In general, S1PR modulators have shown beneficial effects in various models of inflammatory bowel diseases (IBD). The S1PR modulator ozanimod was approved for the treatment of relapsing-remitting MS (e24) in 2019 and then in 2021 for the treatment of moderate-to-severe active ulcerative colitis (40). Many of the participants in the last-mentioned trial had previously been treated with TNF inhibitors, vedolizumab or immune modulators. The dosing for MS and ulcerative colitis is identical and the safety profile, including an increase in liver enzyme levels, susceptibility to infection and macular edema, among other adverse events, appears to be comparable too. The use of some Janus kinase inhibitors has now been evaluated in patients with inflammatory bowel diseases and shown positive effects; tofacitinib has been approved for the treatment of severe ulcerative colitis. As shown above, no data on the use of Janus kinase inhibitors in patients with MS has been reported to date.

Conclusion for clinical practice

Patients with MS and another chronic inflammatory disease pose a particular therapeutic challenge for treating physicians. Close interdisciplinary collaboration between experts in neuroimmunology and the relevant team of specialists is needed when developing personalized treatment strategies.

Conflict of interest
TK received fees for lectures and advisory board services from Novartis Pharma, Roche Pharma, Alexion/Astra Zeneca, Merck, Amgen, Chugai Pharma, UCB, and Biogen.

RS received research funding, contracts for clinical trials, scientific awards or fees for consulting, participation in advisory boards or for lectures from the following organizations: AbbVie, Almirall Hermal, Amgen, Bayer Schering Pharma, Boehringer Ingelheim Pharma, Bruno Bloch Stiftung, Celgene/Amgen, Celgene/Bristol Myers Squibb, Charité Research Organisation, CSL Behring, ICON, IQVIA RDS, Incyte, Janssen-Cilag/Janssen Research & Development, MoonLake Immunotherapeutics, Novartis Pharma, Parexel, Rheinische Friedrich-Wilhelms-Universität Bonn, Sanofi-Aventis, TFS, UCB Biopharma, Universitätsmedizin Greifswald, Wundnetz Berlin-Brandenburg e. V.

MK received lecture/speaker’s fees from Novartis, GSK, AstraZeneca, and MSD, reimbursement of travel costs/congress fees from Sobi and Dr. Schär GmbH, fees for expert opinions from AbbVie, Eligo Biosciences, Enterome, Bristol-Meyers Squibb, and Cell Applications, as well as other financial support from Roche, Genentech, BiomX, and Sanofi.

BS received consulting fees from AbbVie, Abivax, Arena, BMS, Boehringer, CED Service GmbH, Celgene, CT Scout, Endpoint Health, Falk, Forga Software, Galapagos, Gilead, Janssen, Eli Lilly, Materia Prima, Pfizer, Takeda, Pharma Insight, Predictimmune, and PsiCro, as well as funding for continuing medical education from AbbVie, BMS, Boehringer, CED Service GmbH, Falk, Galapagos, Janssen, Eli Lilly, Materia Prima, Pfizer, and Takeda.

SB received funding for continuing medical education from Biogen, Bristol Myers Squibb, Hexal, Merck Healthcare, Novartis, Roche, Sanofi Genzyme, and Teva.

Manuscript received on 12 September 2024, revised version accepted on 13 May 2025

Translated from the original German by Ralf Thoene, M.D.

Correspondence
Prof. Dr. med. Stefan Bittner

References

1. Jakimovski D, Bittner S, Zivadinov R, et al.: Multiple sclerosis. Lancet 2024; 403: 183–202

2. Leal Rato M, Santos M, de Sa J, Ferreira J: Comorbid autoimmune disorders in people with multiple sclerosis: A retrospective cohort study. J Neuroimmunol 2023; 385: 578226

3. Marrie RA, Reider N, Cohen J, et al.: A systematic review of the incidence and prevalence of autoimmune disease in multiple sclerosis. Mult Scler 2015; 21: 282–93

4. Hauer L, Perneczky J, Sellner J: A global view of comorbidity in multiple sclerosis: A systematic review with a focus on regional differences, methodology, and clinical implications. J Neurol 2021; 268: 4066–77

5. Akmatov MK, Holstiege H, Dammertz L, Kohring C, Müller D: Entwicklung der Prävalenz diagnostizierter Autoimmunerkrankungen im Zeitraum 2012–2022. Zentralinstitut für die kassenärztliche Versorgung in Deutschland (Zi). Versorgungsatlas-Bericht Nr 24/05 Berlin 2024.

6. Conrad N, Misra S, Verbakel JY, et al.: Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: A population-based cohort study of 22 million individuals in the UK. Lancet 2023; 401: 1878–90

7. Gupta G, Gelfand JM, Lewis JD: Increased risk for demyelinating diseases in patients with inflammatory bowel disease. Gastroenterology 2005; 129: 819–26

8. Yaqubi K, Kostev K, Klein I, et al.: Inflammatory bowel disease is associated with an increase in the incidence of multiple sclerosis: A retrospective cohort study of 24,934 patients. Eur J Med Res 2024; 29: 186

9. Marrie RA, Patten SB, Tremlett H, Wolfson C, Leung S, Fisk JD: Increased incidence and prevalence of psoriasis in multiple sclerosis. Mult Scler Relat Disord 2017; 13: 81–6

10. Tseng CC, Chang SJ, Tsai WC, et al.: Increased incidence of rheumatoid arthritis in multiple sclerosis: A nationwide cohort study. Medicine (Baltimore) 2016; 95: e3999

11. Liu CY, Tung TH, Lee CY, Chang KH, Wang SH, Chi CC: Association of Multiple Sclerosis with Psoriasis: A systematic review and meta-analysis of observational studies. Am J Clin Dermatol 2019; 20: 201–8

12. Rudick RA, Stuart WH, Calabresi PA, et al.: Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006; 354: 911–23

13. Schwab N, Schneider-Hohendorf T, Melzer N, Cutter G, Wiendl H: Natalizumab-associated PML: Challenges with incidence, resulting risk, and risk stratification. Neurology 2017; 88: 1197–205

14. Brummer T, Ruck T, Meuth SG, Zipp F, Bittner S: Treatment approaches to patients with multiple sclerosis and coexisting autoimmune disorders. Ther Adv Neurol Disord 2021; 14: 17562864211035542

15. Konen FF, Mohn N, Witte T, et al.: Treatment of autoimmunity: The impact of disease-modifying therapies in multiple sclerosis and comorbid autoimmune disorders. Autoimmun Rev 2023; 22: 103312

16. Langley RG, Elewski BE, Lebwohl M, et al.: Secukinumab in plaque psoriasis—results of two phase 3 trials. N Engl J Med 2014; 371: 326–38

17. Fox RJ, Miller DH, Phillips JT, et al.: Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012; 367: 1087–97

18. Gold R, Kappos L, Arnold DL, et al.: Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 2012; 367: 1098–107

19. Tsivgoulis G, Papadimitropoulos GN, Katsanos AH, et al.: Teaching neuroImages: Interferon-induced psoriasis flare in a multiple sclerosis case remits with dimethyl fumarate. Neurology 2017; 89: e188–e9

20. Zecca C, Caporro M, Adami M, Mainetti C, Gobbi C: Fumaric acid esters in psoriasis and multiple sclerosis. Clin Exp Dermatol 2014; 39: 488–91

21. Vaclavkova A, Chimenti S, Arenberger P, et al.: Oral ponesimod in patients with chronic plaque psoriasis: A randomised, double-blind, placebo-controlled phase 2 trial. Lancet 2014; 384: 2036–45

22. Avasarala J, Guduru Z, McLouth CJ, et al.: Use of anti-TNF-alpha therapy in Crohn‘s disease is associated with increased incidence of multiple sclerosis. Mult Scler Relat Disord 2021; 51: 102942

23. Bosch X, Saiz A, Ramos-Casals M, Group BS: Monoclonal antibody therapy-associated neurological disorders. Nat Rev Neurol 2011; 7: 165–72

24. Kopp TI, Delcoigne B, Arkema EV, et al.: Risk of neuroinflammatory events in arthritis patients treated with tumour necrosis factor alpha inhibitors: A collaborative population-based cohort study from Denmark and Sweden. Ann Rheum Dis 2020; 79: 566–72

25. Havrdova E, Belova A, Goloborodko A, et al.: Activity of secukinumab, an anti-IL-17A antibody, on brain lesions in RRMS: Results from a randomized, proof-of-concept study. J Neurol 2016; 263: 1287–95

26. Eyerich K, Asadullah K, Pinter A, et al.: Noninferiority of 16-week vs 8-week guselkumab dosing in super responders for maintaining control of psoriasis: The GUIDE randomized clinical trial. JAMA Dermatol 2024; 160: 953–63

27. Segal BM, Constantinescu CS, Raychaudhuri A, et al.: Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: A phase II, double-blind, placebo-controlled, randomised, dose-ranging study. Lancet Neurol 2008; 7: 796–804

28. Hemmer B: Diagnose und Therapie der Multiplen Sklerose, Neuromyelitis-optica Spektrum-Erkrankungen und MOG-IgG-assoziierten Erkrankungen, S2k-Leitlinie, 2024. In: Deutsche Gesellschaft für Neurologie (eds.): Leitlinien für Diagnostik und Therapie in der Neurologie. https://www.dgn.org/leitlinie/diagnose-und-therapie-der-multiplen-sklerose-neuromyelitis-optica-spektrum-erkrankungen-und-mog-igg-assoziierten-erkrankungen (last accessed on 26 June 2025).

29. Gossec L, Kerschbaumer A, Ferreira RJO, et al.: EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update. Ann Rheum Dis 2024; 83: 706–19

30. Smolen JS, Landewe RBM, Bergstra SA, et al.: EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis 2023; 82: 3–18

31. Hauser SL, Bar-Or A, Comi G, et al.: Ocrelizumab versus Interferon Beta-1a in relapsing Multiple Sclerosis. N Engl J Med 2017; 376: 221–34

32. Montalban X, Hauser SL, Kappos L, et al.: Ocrelizumab versus placebo in primary progressive Multiple Sclerosis. N Engl J Med 2017; 376: 209–20

33. Rigby W, Tony HP, Oelke K, et al.: Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: Results of a forty-eight-week randomized, double-blind, placebo-controlled, parallel-group phase III trial. Arthritis Rheum 2012; 64: 350–9

34. Stohl W, Gomez-Reino J, Olech E, et al.: Safety and efficacy of ocrelizumab in combination with methotrexate in MTX-naive subjects with rheumatoid arthritis: The phase III FILM trial. Ann Rheum Dis 2012; 71: 1289–96

35. Tak PP, Mease PJ, Genovese MC, et al.: Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an inadequate response to at least one tumor necrosis factor inhibitor: Results of a forty-eight-week randomized, double-blind, placebo-controlled, parallel-group phase III trial. Arthritis Rheum 2012; 64: 360–70

36. Taylor PC, Quattrocchi E, Mallett S, Kurrasch R, Petersen J, Chang DJ: Ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, rheumatoid arthritis patients with an inadequate response to methotrexate: A randomised, double-blind, placebo-controlled clinical trial. Ann Rheum Dis 2011; 70: 2119–25

37. Schwab N, Schneider-Hohendorf T, Hoyt T, et al.: Anti-JCV serology during natalizumab treatment: Review and meta-analysis of 17 independent patient cohorts analyzing anti-John Cunningham polyoma virus sero-conversion rates under natalizumab treatment and differences between technical and biological sero-converters. Mult Scler 2018; 24: 563–73

38. Feagan BG, Rutgeerts P, Sands BE, et al.: Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2013; 369: 699–710

39. Sandborn WJ, Feagan BG, Rutgeerts P, et al.: Vedolizumab as induction and maintenance therapy for Crohn‘s disease. N Engl J Med 2013; 369: 711–21

40. Sandborn WJ, Feagan BG, D‘Haens G, et al.: Ozanimod as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2021; 385: 1280–91

e1. Harroud A, Hafler DA: Common genetic factors among autoimmune diseases. Science 2023; 380: 485–90

e2. Ghoreschi K, Balato A, Enerback C, Sabat R: Therapeutics targeting the IL-23 and IL-17 pathway in psoriasis. Lancet 2021; 397: 754–66

e3. Sabat R, Gudjonsson JE, Brembilla NC, van Straalen KR, Wolk K: Biology of interleukin-17 and novel therapies for hidradenitis suppurativa. J Interferon Cytokine Res 2023; 43: 544–56

e4. Nieboer C, de Hoop D, van Loenen AC, Langendijk PN, van Dijk E: Systemic therapy with fumaric acid derivates: New possibilities in the treatment of psoriasis. J Am Acad Dermatol 1989; 20: 601–8

e5. McGinley MP, Cohen JA: Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions. Lancet 2021; 398: 1184–94

e6. Darwin E, Romanelli P, Lev-Tov H: Ocrelizumab-induced psoriasiform dermatitis in a patient with multiple sclerosis. Dermatol Online J 2018; 24: 13030/qt220859qb

e7. Venables ZC, Swart SS, Soon CS: Palmoplantar pustulosis secondary to rituximab: A case report and literature review. Clin Exp Dermatol 2015; 40: 451–2

e8. Emma C, Vesela P, Kay P, et al.: Psoriasiform dermatitis following ocrelizumab in relapsing-remitting multiple sclerosis: Case report and literature review. Mult Scler 2024; 30: 893–7

e9. Kolsche T, Willison AG, Meuth SG, et al.: Ofatumumab-induced severe reactivation of psoriasis in a patient with multiple sclerosis. Mult Scler 2024; 30: 1086–8

e10. Leone GM, Mangano K, Petralia MC, Nicoletti F, Fagone P: Past, present and (foreseeable) future of biological anti-TNF alpha therapy. J Clin Med 2023; 12: 1630

e11. Gregory AP, Dendrou CA, Attfield KE, et al.: TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature 2012; 488: 508–11

e12. Ronin E, Pouchy C, Khosravi M, et al.: Tissue-restricted control of established central nervous system autoimmunity by TNF receptor 2-expressing Treg cells. Proc Natl Acad Sci U S A 2021; 118: e2014043118

e13. Ashtari F, Savoj MR: Effects of low dose methotrexate on relapsing-remitting multiple sclerosis in comparison to Interferon beta-1alpha: A randomized controlled trial. J Res Med Sci 2011; 16: 457–62.

e14. Goodkin DE, Rudick RA, VanderBrug Medendorp S, Daughtry MM, Van Dyke C: Low-dose oral methotrexate in chronic progressive multiple sclerosis: Analyses of serial MRIs. Neurology 1996; 47: 1153–7

e15. Cohen SB, Emery P, Greenwald MW, et al.: Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 2006; 54: 2793–806

e16. Svenningsson A, Frisell T, Burman J, et al.: Safety and efficacy of rituximab versus dimethyl fumarate in patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome in Sweden: A rater-blinded, phase 3, randomised controlled trial. Lancet Neurol 2022; 21: 693–703

e17. Beauchemin P, Carruthers R: MS arising during Tocilizumab therapy for rheumatoid arthritis. Mult Scler 2016; 22: 254–6

e18. Sato H, Kobayashi D, Abe A, et al.: Tocilizumab treatment safety in rheumatoid arthritis in a patient with multiple sclerosis: A case report. BMC Res Notes 2014; 7: 641

e19. Eibschutz B, Baird SM, Weisman MH, et al.: Oral 2-chlorodeoxyadenosine in psoriatic arthritis. A preliminary report. Arthritis Rheum 1995; 38: 1604–9

e20. Schirmer M, Mur E, Pfeiffer KP, Thaler J, Konwalinka G: The safety profile of low-dose cladribine in refractory rheumatoid arthritis. A pilot trial. Scand J Rheumatol 1997; 26: 376–9

e21. Rudick RA, Stuart WH, Calabresi PA, et al.: Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006; 354: 911–23

e22. Polman CH, O’Connor PW, Havrdova E, et al.: A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354: 899–910

e23. Sandborn WJ, Colombel JF, Enns R, et al.: Natalizumab induction and maintenance therapy for Crohn‘s disease. N Engl J Med; 353: 1912–25

e24. Cohen JA, Comi G, Selmaj KW, et al.: Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol 2019; 18: 1021–33